WorldWideScience

Sample records for aminoglycoside antibiotic activity

  1. Collateral sensitivity between aminoglycosides and beta-lactam antibiotics depends on active proton pumps.

    Science.gov (United States)

    Azimi, Leila; Rastegar Lari, Abdolaziz

    2017-11-01

    Selection inversion is the hypothesis for antibiotic resistant inhabitation in bacteria and collateral sensitivity is one of the proposed phenomena for achievement of this hypothesis. The presence of collateral sensitivity associated with the proton motivation pump between the aminoglycosides and beta-lactam group of antibiotics is one of the examples of collateral sensitivity in some studies. The aim of this study was to demonstrate that collateral sensitivity between aminoglycosides and beta-lactam antibiotics associated with proton motivation pump may not be true in all cases. In this study, 100 Pseudomonas aeruginosa were surveyed. Gentamicin and imipenem-resistant strains were confirmed by disc diffusion method and MIC. Active proton motivation pumps were screened by pumps inhibitor. Semi-quantitative Real-Time PCR assay was used to confirm gene overexpression. Seventy-six and 79 out of 100 strains were resistant to gentamicin and imipenem, respectively. Seventy-five strains were resistant to both gentamicin and imipenem. The results of proton pump inhibitor test showed the involvement of active proton motivation pump in 22 of 75 imipenem- and gentamicin-resistant strains. According to Real - Time PCR assay, mexX efflux gene was overexpressed in the majority of isolates tested. The collateral sensitivity effect cannot explain the involvement of active proton motivation pumps in both imipenem and gentamicin-resistant strains simultaneously. Active and/or inactive proton pump in gentamicin-sensitive and/or resistant strains cannot be a suitable example for explanation of collateral sensitivity between aminoglycosides and beta-lactam antibiotics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Overcoming Aminoglycoside Enzymatic Resistance: Design of Novel Antibiotics and Inhibitors

    Directory of Open Access Journals (Sweden)

    Sandra G. Zárate

    2018-01-01

    Full Text Available Resistance to aminoglycoside antibiotics has had a profound impact on clinical practice. Despite their powerful bactericidal activity, aminoglycosides were one of the first groups of antibiotics to meet the challenge of resistance. The most prevalent source of clinically relevant resistance against these therapeutics is conferred by the enzymatic modification of the antibiotic. Therefore, a deeper knowledge of the aminoglycoside-modifying enzymes and their interactions with the antibiotics and solvent is of paramount importance in order to facilitate the design of more effective and potent inhibitors and/or novel semisynthetic aminoglycosides that are not susceptible to modifying enzymes.

  3. Antibiotic stress-induced modulation of the endoribonucleolytic activity of RNase III and RNase G confers resistance to aminoglycoside antibiotics in Escherichia coli

    Science.gov (United States)

    Song, Wooseok; Kim, Yong-Hak; Sim, Se-Hoon; Hwang, Soonhye; Lee, Jung-Hyun; Lee, Younghoon; Bae, Jeehyeon; Hwang, Jihwan; Lee, Kangseok

    2014-01-01

    Here, we report a resistance mechanism that is induced through the modulation of 16S ribosomal RNA (rRNA) processing on the exposure of Escherichia coli cells to aminoglycoside antibiotics. We observed decreased expression levels of RNase G associated with increased RNase III activity on rng mRNA in a subgroup of E. coli isolates that transiently acquired resistance to low levels of kanamycin or streptomycin. Analyses of 16S rRNA from the aminoglycoside-resistant E. coli cells, in addition to mutagenesis studies, demonstrated that the accumulation of 16S rRNA precursors containing 3–8 extra nucleotides at the 5’ terminus, which results from incomplete processing by RNase G, is responsible for the observed aminoglycoside resistance. Chemical protection, mass spectrometry analysis and cell-free translation assays revealed that the ribosomes from rng-deleted E. coli have decreased binding capacity for, and diminished sensitivity to, streptomycin and neomycin, compared with wild-type cells. It was observed that the deletion of rng had similar effects in Salmonella enterica serovar Typhimurium strain SL1344. Our findings suggest that modulation of the endoribonucleolytic activity of RNase III and RNase G constitutes a previously uncharacterized regulatory pathway for adaptive resistance in E. coli and related gram-negative bacteria to aminoglycoside antibiotics. PMID:24489121

  4. Antibiotic stress-induced modulation of the endoribonucleolytic activity of RNase III and RNase G confers resistance to aminoglycoside antibiotics in Escherichia coli.

    Science.gov (United States)

    Song, Wooseok; Kim, Yong-Hak; Sim, Se-Hoon; Hwang, Soonhye; Lee, Jung-Hyun; Lee, Younghoon; Bae, Jeehyeon; Hwang, Jihwan; Lee, Kangseok

    2014-04-01

    Here, we report a resistance mechanism that is induced through the modulation of 16S ribosomal RNA (rRNA) processing on the exposure of Escherichia coli cells to aminoglycoside antibiotics. We observed decreased expression levels of RNase G associated with increased RNase III activity on rng mRNA in a subgroup of E. coli isolates that transiently acquired resistance to low levels of kanamycin or streptomycin. Analyses of 16S rRNA from the aminoglycoside-resistant E. coli cells, in addition to mutagenesis studies, demonstrated that the accumulation of 16S rRNA precursors containing 3-8 extra nucleotides at the 5' terminus, which results from incomplete processing by RNase G, is responsible for the observed aminoglycoside resistance. Chemical protection, mass spectrometry analysis and cell-free translation assays revealed that the ribosomes from rng-deleted E. coli have decreased binding capacity for, and diminished sensitivity to, streptomycin and neomycin, compared with wild-type cells. It was observed that the deletion of rng had similar effects in Salmonella enterica serovar Typhimurium strain SL1344. Our findings suggest that modulation of the endoribonucleolytic activity of RNase III and RNase G constitutes a previously uncharacterized regulatory pathway for adaptive resistance in E. coli and related gram-negative bacteria to aminoglycoside antibiotics.

  5. DNA-Aptamers Binding Aminoglycoside Antibiotics

    Directory of Open Access Journals (Sweden)

    Nadia Nikolaus

    2014-02-01

    Full Text Available Aptamers are short, single stranded DNA or RNA oligonucleotides that are able to bind specifically and with high affinity to their non-nucleic acid target molecules. This binding reaction enables their application as biorecognition elements in biosensors and assays. As antibiotic residues pose a problem contributing to the emergence of antibiotic-resistant pathogens and thereby reducing the effectiveness of the drug to fight human infections, we selected aptamers targeted against the aminoglycoside antibiotic kanamycin A with the aim of constructing a robust and functional assay that can be used for water analysis. With this work we show that aptamers that were derived from a Capture-SELEX procedure targeting against kanamycin A also display binding to related aminoglycoside antibiotics. The binding patterns differ among all tested aptamers so that there are highly substance specific aptamers and more group specific aptamers binding to a different variety of aminoglycoside antibiotics. Also the region of the aminoglycoside antibiotics responsible for aptamer binding can be estimated. Affinities of the different aptamers for their target substance, kanamycin A, are measured with different approaches and are in the micromolar range. Finally, the proof of principle of an assay for detection of kanamycin A in a real water sample is given.

  6. Aminoglycoside antibiotics and autism: a speculative hypothesis

    Directory of Open Access Journals (Sweden)

    Manev Hari

    2001-10-01

    Full Text Available Abstract Background Recently, it has been suspected that there is a relationship between therapy with some antibiotics and the onset of autism; but even more curious, some children benefited transiently from a subsequent treatment with a different antibiotic. Here, we speculate how aminoglycoside antibiotics might be associated with autism. Presentation We hypothesize that aminoglycoside antibiotics could a trigger the autism syndrome in susceptible infants by causing the stop codon readthrough, i.e., a misreading of the genetic code of a hypothetical critical gene, and/or b improve autism symptoms by correcting the premature stop codon mutation in a hypothetical polymorphic gene linked to autism. Testing Investigate, retrospectively, whether a link exists between aminoglycoside use (which is not extensive in children and the onset of autism symptoms (hypothesis "a", or between amino glycoside use and improvement of these symptoms (hypothesis "b". Whereas a prospective study to test hypothesis "a" is not ethically justifiable, a study could be designed to test hypothesis "b". Implications It should be stressed that at this stage no direct evidence supports our speculative hypothesis and that its main purpose is to initiate development of new ideas that, eventually, would improve our understanding of the pathobiology of autism.

  7. Synergistic ototoxicity due to noise exposure and aminoglycoside antibiotics.

    Science.gov (United States)

    Li, Hongzhe; Steyger, Peter S

    2009-01-01

    Acoustic exposure to high intensity and/or prolonged noise causes temporary or permanent threshold shifts in auditory perception, reflected by reversible or irreversible damage in the cochlea. Aminoglycoside antibiotics, used for treating or preventing life-threatening bacterial infections, also induce cytotoxicity in the cochlea. Combined noise and aminoglycoside exposure, particularly in neonatal intensive care units, can lead to auditory threshold shifts greater than simple summation of the two insults. The synergistic toxicity of acoustic exposure and aminoglycoside antibiotics is not limited to simultaneous exposures. Prior acoustic insult which does not result in permanent threshold shifts potentiates aminoglycoside ototoxicity. In addition, exposure to subdamaging doses of aminoglycosides aggravates noise-induced cochlear damage. The mechanisms by which aminoglycosides cause auditory dysfunction are still being unraveled, but likely include the following: 1) penetration into the endolymphatic fluid of the scala media, 2) permeation of nonselective cation channels on the apical surface of hair cells, and 3) generation of toxic reactive oxygen species and interference with other cellular pathways. Here we discuss the effect of combined noise and aminoglycoside exposure to identify pivotal synergistic events that can potentiate ototoxicity, in addition to a current understanding of aminoglycoside trafficking within the cochlea. Preventing the ototoxic synergy of noise and aminoglycosides is best achieved by using non-ototoxic bactericidal drugs, and by attenuating perceived noise intensity when life-saving aminoglycoside therapy is required.

  8. Ribosomal Protein S12 and Aminoglycoside Antibiotics Modulate A-site mRNA Cleavage and Transfer-Messenger RNA Activity in Escherichia coli*

    OpenAIRE

    Holberger, Laura E.; Hayes, Christopher S.

    2009-01-01

    Translational pausing in Escherichia coli can lead to mRNA cleavage within the ribosomal A-site. A-site mRNA cleavage is thought to facilitate transfer-messenger RNA (tmRNA)·SmpB- mediated recycling of stalled ribosome complexes. Here, we demonstrate that the aminoglycosides paromomycin and streptomycin inhibit A-site cleavage of stop codons during inefficient translation termination. Aminoglycosides also induced stop codon read-through, suggesting that these antibiotics alleviate ribosome pa...

  9. Chitosan conjugation enables intracellular bacteria susceptible to aminoglycoside antibiotic.

    Science.gov (United States)

    Mu, Haibo; Niu, Hong; Wang, Dongdong; Sun, Feifei; Sun, Yuelin; Duan, Jinyou

    2016-11-01

    Most chronic infections are difficult to eradicate because bacteria capable of surviving in host-infected cells may be protected from the killing actions of antibiotics, leading to therapy failures and disease relapses. Here we demonstrated that covalent-coupling chitosan to streptomycin significantly improved intracellular bactericidal capacity towards multiple organisms within phagocytic or nonphagocytic cells. Structure-activity relationship investigations indicated that antibiotic contents, molecular size and positive charges of the conjugate were the key to retain this intracellular bactericidal activity. Mechanistic insight demonstrated the conjugate was capable to target and eliminate endocytic or endosomal escaped bacteria through facilitating the direct contact between the antibiotic and intracellular organism. In vivo acute infection models indicated that compared to equal dose of the antibiotic, chitosan-streptomycin (C-S) conjugate and especially the human serum album binding chitosan-streptomycin conjugate (HCS) complex formed by human serum album and C-S conjugate greatly decreased the bacteria burden in the spleen and liver in both wild type and immuno-suppressive mice. Furthermore, the HCS complex remarkably reduced mortality of infected TLR2 deficient mice, mimicking immune-compromised persons who were more susceptible to bacterial infections. These findings might open up a new avenue to combat intracellular bacterial infection by aminoglycosides antibiotics at a lower effective dose. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. Cloning, overexpression, and purification of aminoglycoside antibiotic nucleotidyltransferase (2'')-Ia: conformational studies with bound substrates.

    Science.gov (United States)

    Ekman, D R; DiGiammarino, E L; Wright, E; Witter, E D; Serpersu, E H

    2001-06-19

    Aminoglycoside nucleotidyltransferase (2'')-Ia [ANT (2'')-Ia] was cloned from Pseudomonas aeruginosa and purified from overexpressing Escherichia coli BL21(DE3) cells. The first enzyme-bound conformation of an aminoglycoside antibiotic in the active site of an aminoglycoside nucleotidyltransferase was determined using the purified aminoglycoside nucleotidyltransferase (2' ')-Ia. The conformation of the aminoglycoside antibiotic isepamicin, a psuedo-trisaccharide, bound to aminoglycoside nucleotidyltransferase (2' ')-Ia has been determined using NMR spectroscopy. Molecular modeling, employing experimentally determined interproton distances, resulted in two different enzyme-bound conformations (conformer 1 and conformer 2) of isepamicin. Conformer 1 was by far the major conformer defined by the following average glycosidic dihedral angles: PhiBC = -65.26 +/- 1.63 degrees and PsiBC = -54.76 +/- 4.64 degrees. Conformer 1 was further subdivided into one major (conformer 1a) and two minor components (conformers 1b and 1c) based on the comparison of glycosidic dihedral angles PhiAB and PsiAB. The arrangement of substrates in the enzyme.metal-ATP.isepamicin complex was determined on the basis of the measured effect of the paramagnetic substrate analogue Cr(H2O)4ATP on the relaxation rates of substrate protons which were used to determine relative distances of isepamicin protons to the Cr3+. Both conformers of isepamicin yielded arrangements that satisfied the NOE restraints and the observed paramagnetic effects of Cr(H2O)4ATP. It has been suggested that aminoglycosides use both electrostatic interactions and hydrogen bonds in binding to RNA and that the contacts made by the A and B rings to RNA are the most important for binding [Fourmy, D., Recht, M. I., Blanchard, S. C., and Puglisi, J. D. (1996) Science 274, 1367-1371]. Comparisons based on the determined conformations of enzyme-bound aminoglycoside antibiotics also suggested that interactions of rings A and B with

  11. Ribosomal Protein S12 and Aminoglycoside Antibiotics Modulate A-site mRNA Cleavage and Transfer-Messenger RNA Activity in Escherichia coli*

    Science.gov (United States)

    Holberger, Laura E.; Hayes, Christopher S.

    2009-01-01

    Translational pausing in Escherichia coli can lead to mRNA cleavage within the ribosomal A-site. A-site mRNA cleavage is thought to facilitate transfer-messenger RNA (tmRNA)·SmpB- mediated recycling of stalled ribosome complexes. Here, we demonstrate that the aminoglycosides paromomycin and streptomycin inhibit A-site cleavage of stop codons during inefficient translation termination. Aminoglycosides also induced stop codon read-through, suggesting that these antibiotics alleviate ribosome pausing during termination. Streptomycin did not inhibit A-site cleavage in rpsL mutants, which express streptomycin-resistant variants of ribosomal protein S12. However, rpsL strains exhibited reduced A-site mRNA cleavage compared with rpsL+ cells. Additionally, tmRNA·SmpB-mediated SsrA peptide tagging was significantly reduced in several rpsL strains but could be fully restored in a subset of mutants when treated with streptomycin. The streptomycin-dependent rpsL(P90K) mutant also showed significantly lower levels of A-site cleavage and tmRNA·SmpB activity. Mutations in rpsD (encoding ribosomal protein S4), which suppressed streptomycin dependence, were able to partially restore A-site cleavage to rpsL(P90K) cells but failed to increase tmRNA·SmpB activity. Taken together, these results show that perturbations to A-site structure and function modulate A-site mRNA cleavage and tmRNA·SmpB activity. We propose that tmRNA·SmpB binds to streptomycin-resistant rpsL ribosomes less efficiently, leading to a partial loss of ribosome rescue function in these mutants. PMID:19776006

  12. Ribosomal protein S12 and aminoglycoside antibiotics modulate A-site mRNA cleavage and transfer-messenger RNA activity in Escherichia coli.

    Science.gov (United States)

    Holberger, Laura E; Hayes, Christopher S

    2009-11-13

    Translational pausing in Escherichia coli can lead to mRNA cleavage within the ribosomal A-site. A-site mRNA cleavage is thought to facilitate transfer-messenger RNA (tmRNA).SmpB- mediated recycling of stalled ribosome complexes. Here, we demonstrate that the aminoglycosides paromomycin and streptomycin inhibit A-site cleavage of stop codons during inefficient translation termination. Aminoglycosides also induced stop codon read-through, suggesting that these antibiotics alleviate ribosome pausing during termination. Streptomycin did not inhibit A-site cleavage in rpsL mutants, which express streptomycin-resistant variants of ribosomal protein S12. However, rpsL strains exhibited reduced A-site mRNA cleavage compared with rpsL(+) cells. Additionally, tmRNA.SmpB-mediated SsrA peptide tagging was significantly reduced in several rpsL strains but could be fully restored in a subset of mutants when treated with streptomycin. The streptomycin-dependent rpsL(P90K) mutant also showed significantly lower levels of A-site cleavage and tmRNA.SmpB activity. Mutations in rpsD (encoding ribosomal protein S4), which suppressed streptomycin dependence, were able to partially restore A-site cleavage to rpsL(P90K) cells but failed to increase tmRNA.SmpB activity. Taken together, these results show that perturbations to A-site structure and function modulate A-site mRNA cleavage and tmRNA.SmpB activity. We propose that tmRNA.SmpB binds to streptomycin-resistant rpsL ribosomes less efficiently, leading to a partial loss of ribosome rescue function in these mutants.

  13. In vitro studies with UK-18,892, a new aminoglycoside antibiotic.

    Science.gov (United States)

    Jevons, S; Cheeseman, H E; Brammer, K W

    1978-09-01

    The antibacterial activity of UK-18,892, a new semisynthetic aminoglycoside, was examined against aminoglycoside-susceptible and aminoglycoside-resistant clinical isolates of gram-negative bacilli and Staphylococcus aureus. UK-18,892 had a similar degree of activity to those of amikacin and kanamycin A against aminoglycoside-susceptible bacteria but was less potent than gentamicin against all isolates except Providencia spp. UK-18,892 was highly active against aminoglycoside-resistant bacteria, inhibiting 93% of the 268 isolates examined at 12.5 mug/ml. Amikacin was similarly active, whereas gentamicin inhibited only 14% of these isolates at 12.5 mug/ml.

  14. Structural and molecular basis for resistance to aminoglycoside antibiotics by the adenylyltransferase ANT(2″)-Ia.

    Science.gov (United States)

    Cox, Georgina; Stogios, Peter J; Savchenko, Alexei; Wright, Gerard D

    2015-01-06

    The aminoglycosides are highly effective broad-spectrum antimicrobial agents. However, their efficacy is diminished due to enzyme-mediated covalent modification, which reduces affinity of the drug for the target ribosome. One of the most prevalent aminoglycoside resistance enzymes in Gram-negative pathogens is the adenylyltransferase ANT(2″)-Ia, which confers resistance to gentamicin, tobramycin, and kanamycin. Despite the importance of this enzyme in drug resistance, its structure and molecular mechanism have been elusive. This study describes the structural and mechanistic basis for adenylylation of aminoglycosides by the ANT(2″)-Ia enzyme. ANT(2″)-Ia confers resistance by magnesium-dependent transfer of a nucleoside monophosphate (AMP) to the 2″-hydroxyl of aminoglycoside substrates containing a 2-deoxystreptamine core. The catalyzed reaction follows a direct AMP transfer mechanism from ATP to the substrate antibiotic. Central to catalysis is the coordination of two Mg(2+) ions, positioning of the modifiable substrate ring, and the presence of a catalytic base (Asp86). Comparative structural analysis revealed that ANT(2″)-Ia has a two-domain structure with an N-terminal active-site architecture that is conserved among other antibiotic nucleotidyltransferases, including Lnu(A), LinB, ANT(4')-Ia, ANT(4″)-Ib, and ANT(6)-Ia. There is also similarity between the nucleotidyltransferase fold of ANT(2″)-Ia and DNA polymerase β. This similarity is consistent with evolution from a common ancestor, with the nucleotidyltransferase fold having adapted for activity against chemically distinct molecules. IMPORTANCE  : To successfully manage the threat associated with multidrug-resistant infectious diseases, innovative therapeutic strategies need to be developed. One such approach involves the enhancement or potentiation of existing antibiotics against resistant strains of bacteria. The reduction in clinical usefulness of the aminoglycosides is a particular

  15. Effects of the aminoglycoside antibiotics, streptomycin and neomycin, on neuromuscular transmission. I. Presynaptic considerations.

    Science.gov (United States)

    Fiekers, J F

    1983-06-01

    The effects of two aminoglycoside antibiotics, streptomycin and neomycin, were studied in voltage-clamped transected twitch fibers of the costocutaneous muscles of garter snakes (species Thamnophis). The concentration-dependent effects of each antibiotic were quantitated by measuring miniature end-plate currents (mepcs) and evoked end-plate currents (epcs) in a single fiber before and in the presence of a wide range of concentrations of each antibiotic. The amplitude and the kinetics of these currents were studied and estimates of the quantal content of evoked transmitter release determined by the direct method of mean ratios, epc/mepc. A distinct separation was obtained between the concentrations of each antibiotic which demonstrated either pre- or postsynaptic actions. Both streptomycin and neomycin produced a concentration-dependent reduction in epc amplitude at concentrations which did not reduce mepc amplitude. Thus, the primary site of action for these antibiotics was considered of presynaptic origin. Streptomycin was approximately one-tenth as active as neomycin in reducing quantal release of acetylcholine. The marked depression in epc amplitude and quantal content produced by high concentrations of each antibiotic were reversed by elevating the external calcium concentration. Double logarithmic plots of the relationship between external calcium concentration and epc amplitude yielded a slope of approximately 3.8 in control physiological solution. In the presence of blocking concentrations of each antibiotic, increasing the external calcium concentration caused a parallel shift to the right of this relationship. These results suggest that the major mechanism for the neuromuscular depression produced by these aminoglycoside antibiotics is a competitive antagonism with calcium for a common presynaptic site required for evoked transmitter release.

  16. Identification of aminotransferase genes for biosynthesis of aminoglycoside antibiotics from soil DNA.

    Science.gov (United States)

    Nagaya, Atsushi; Takeyama, Satoko; Tamegai, Hideyuki

    2005-07-01

    Aminoglycoside has been known as a clinically important antibiotic for a long time, but genetic information for the biosynthesis of aminoglycoside is still insufficient. In this study, we tried to clone aminoglycoside-biosynthetic genes from soil DNA for accumulation of genetic information. We chose the genes encoding L-glutamine:(2-deoxy-)scyllo-inosose aminotransferase as the target, because it is specific for all types of aminoglycoside biosynthesis. By degenerate PCR, we obtained 33 individual clones that were homologous with aminotransferase genes in aminoglycoside biosynthesis. Phylogenetic analysis and alignment of these genes showed that horizontal gene transfer has occurred in the soil. Among these, several quite interesting genes were obtained. Some genes probably originated from non-actinomycetes, and some were far from the known homologs. These genes can be useful markers for the isolation of entire gene clusters and originating organisms.

  17. Glomerular nephrotoxicity of aminoglycosides

    International Nuclear Information System (INIS)

    Martinez-Salgado, Carlos; Lopez-Hernandez, Francisco J.; Lopez-Novoa, Jose M.

    2007-01-01

    Aminoglycoside antibiotics are the most commonly used antibiotics worldwide in the treatment of Gram-negative bacterial infections. However, aminoglycosides induce nephrotoxicity in 10-20% of therapeutic courses. Aminoglycoside-induced nephrotoxicity is characterized by slow rises in serum creatinine, tubular necrosis and marked decreases in glomerular filtration rate and in the ultrafiltration coefficient. Regulation of the ultrafiltration coefficient depends on the activity of intraglomerular mesangial cells. The mechanisms responsible for tubular nephrotoxicity of aminoglycosides have been intensively reviewed previously, but glomerular toxicity has received less attention. The purpose of this review is to critically assess the published literature regarding the toxic mechanisms of action of aminoglycosides on renal glomeruli and mesangial cells. The main goal of this review is to provide an actualized and mechanistic vision of pathways involved in glomerular toxic effects of aminoglycosides

  18. Therapeutic drug monitoring by radioimmunoassay: Determination of aminoglycoside antibiotics and vancomycin in plasma

    International Nuclear Information System (INIS)

    Glaubitt, D.; Drechsler, H.J.; Knoch, K.; Siafarikas, K.

    1984-01-01

    Radioimmunoassay of aminoglycoside antibiotics (gentamicin, tobramycin, netilmicin) or vancomycin in plasma may considerably aid to assess their appropriate dosage and, if necessary, to rapidly adjust it to the assumed requirement. Thus the dosage of the antibiotic is kept large enough as to lead to the desired therapeutic result but not as high as to cause side effects. (orig.)

  19. Radioimmunoassay and radioenzymatic assay of a new aminoglycoside antibiotic, netilmicin

    International Nuclear Information System (INIS)

    Broughton, A.; Strong, J.E.; Pickering, L.K.; Knight, J.; Bodey, G.P.

    1978-01-01

    A radioimmunoassay and a radioenzymatic assay for netilmicin, a new aminoglycoside, were developed in our laboratories to assist in the study of the pharmacology of the drug and establish values for use in its monitoring. The assays are sensitive, precise, and rapid, giving results that correlate (r = 0.90) with each other and with those of a microbiological assay in which Klebsiella pneumoniae is used as the test organism. Preliminary pharmacological studies show the drug to have a biological half-life of 135 min, which is comparable to that for other aminoglycosides

  20. Highly stable, protein capped gold nanoparticles as effective drug delivery vehicles for amino-glycosidic antibiotics

    International Nuclear Information System (INIS)

    Rastogi, Lori; Kora, Aruna Jyothi; Arunachalam, J.

    2012-01-01

    A method for the production of highly stable gold nanoparticles (Au NP) was optimized using sodium borohydride as reducing agent and bovine serum albumin as capping agent. The synthesized nanoparticles were characterized using UV–visible spectroscopy, transmission electron microscopy, X‐ray diffraction (XRD) and dynamic light scattering techniques. The formation of gold nanoparticles was confirmed from the appearance of pink colour and an absorption maximum at 532 nm. These protein capped nanoparticles exhibited excellent stability towards pH modification and electrolyte addition. The produced nanoparticles were found to be spherical in shape, nearly monodispersed and with an average particle size of 7.8 ± 1.7 nm. Crystalline nature of the nanoparticles in face centered cubic structure is confirmed from the selected‐area electron diffraction and XRD patterns. The nanoparticles were functionalized with various amino-glycosidic antibiotics for utilizing them as drug delivery vehicles. Using Fourier transform infrared spectroscopy, the possible functional groups of antibiotics bound to the nanoparticle surface have been examined. These drug loaded nanoparticle solutions were tested for their antibacterial activity against Gram-negative and Gram-positive bacterial strains, by well diffusion assay. The antibiotic conjugated Au NP exhibited enhanced antibacterial activity, compared to pure antibiotic at the same concentration. Being protein capped and highly stable, these gold nanoparticles can act as effective carriers for drugs and might have considerable applications in the field of infection prevention and therapeutics. - Highlights: ► Method for NaBH 4 reduced and BSA capped gold nanoparticle was standardized. ► Nanoparticles were spherical and nearly monodispersed with a size of 7.8 nm. ► Nanoparticles are extremely stable towards pH modification and electrolyte addition. ► Antibiotic conjugated nanoparticles exhibited enhanced antibacterial activity

  1. Highly stable, protein capped gold nanoparticles as effective drug delivery vehicles for amino-glycosidic antibiotics

    Energy Technology Data Exchange (ETDEWEB)

    Rastogi, Lori; Kora, Aruna Jyothi; Arunachalam, J., E-mail: aruncccm@gmail.com

    2012-08-01

    A method for the production of highly stable gold nanoparticles (Au NP) was optimized using sodium borohydride as reducing agent and bovine serum albumin as capping agent. The synthesized nanoparticles were characterized using UV-visible spectroscopy, transmission electron microscopy, X-ray diffraction (XRD) and dynamic light scattering techniques. The formation of gold nanoparticles was confirmed from the appearance of pink colour and an absorption maximum at 532 nm. These protein capped nanoparticles exhibited excellent stability towards pH modification and electrolyte addition. The produced nanoparticles were found to be spherical in shape, nearly monodispersed and with an average particle size of 7.8 {+-} 1.7 nm. Crystalline nature of the nanoparticles in face centered cubic structure is confirmed from the selected-area electron diffraction and XRD patterns. The nanoparticles were functionalized with various amino-glycosidic antibiotics for utilizing them as drug delivery vehicles. Using Fourier transform infrared spectroscopy, the possible functional groups of antibiotics bound to the nanoparticle surface have been examined. These drug loaded nanoparticle solutions were tested for their antibacterial activity against Gram-negative and Gram-positive bacterial strains, by well diffusion assay. The antibiotic conjugated Au NP exhibited enhanced antibacterial activity, compared to pure antibiotic at the same concentration. Being protein capped and highly stable, these gold nanoparticles can act as effective carriers for drugs and might have considerable applications in the field of infection prevention and therapeutics. - Highlights: Black-Right-Pointing-Pointer Method for NaBH{sub 4} reduced and BSA capped gold nanoparticle was standardized. Black-Right-Pointing-Pointer Nanoparticles were spherical and nearly monodispersed with a size of 7.8 nm. Black-Right-Pointing-Pointer Nanoparticles are extremely stable towards pH modification and electrolyte addition. Black

  2. Effect of mutations in the A site of 16 S rRNA on aminoglycoside antibiotic-ribosome interaction

    DEFF Research Database (Denmark)

    Recht, M I; Douthwaite, S; Dahlquist, K D

    1999-01-01

    antibiotics, which also interact with this region of rRNA. Mutations of certain nucleotides in rRNA reduce aminoglycoside binding affinity, as previously demonstrated using a model RNA oligonucleotide system. Here, predictions from the oligonucleotide system were tested in the ribosome by mutation...... for the aminoglycoside paromomycin, whereas no discernible reduction in affinity was observed with 1406 mutant ribosomes. These data are consistent with prior NMR structural determination of aminoglycoside interaction with the decoding region, and further our understanding of how aminoglycoside resistance can...

  3. Involvement of an active efflux system in the natural resistance of Pseudomonas aeruginosa to aminoglycosides.

    Science.gov (United States)

    Aires, J R; Köhler, T; Nikaido, H; Plésiat, P

    1999-11-01

    A mutant, named 11B, hypersusceptible to aminoglycosides, tetracycline, and erythromycin was isolated after Tn501 insertion mutagenesis of Pseudomonas aeruginosa PAO1. Cloning and sequencing experiments showed that 11B was deficient in an, at that time, unknown active efflux system that contains homologs of MexAB. This locus also contained a putative regulatory gene, mexZ, transcribed divergently from the efflux operon. Introduction of a recombinant plasmid that carries the genes of the efflux system restored the resistance of 11B to parental levels, whereas overexpression of these genes strongly increased the MICs of substrate antibiotics for the PAO1 host. Antibiotic accumulation studies confirmed that this new system is an energy-dependent active efflux system that pumps out aminoglycosides. Furthermore, this system appeared to function with an outer membrane protein, OprM. While the present paper was being written and reviewed, genes with a sequence identical to our pump genes, mexXY of P. aeruginosa, have been reported to increase resistance to erythromycin, fluoroquinolones, and organic cations in Escherichia coli hosts, although efflux of aminoglycosides was not examined (Mine et al., Antimicrob. Agents Chemother. 43:415-417, 1999). Our study thus shows that the MexXY system plays an important role in the intrinsic resistance of P. aeruginosa to aminoglycosides. Although overexpression of MexXY increased the level of resistance to fluoroquinolones, disruption of the mexXY operon in P. aeruginosa had no detectable effect on susceptibility to these agents.

  4. Aminoglycoside Antibiotics: New Insights into the Biosynthetic Machinery of Old Drugs.

    Science.gov (United States)

    Kudo, Fumitaka; Eguchi, Tadashi

    2016-02-01

    2-Deoxystreptamine (2DOS) is the unique chemically stable aminocyclitol scaffold of clinically important aminoglycoside antibiotics such as neomycin, kanamycin, and gentamicin, which are produced by Actinomycetes. The 2DOS core can be decorated with various deoxyaminosugars to make structurally diverse pseudo-oligosaccharides. After the discovery of biosynthetic gene clusters for 2DOS-containing aminoglycoside antibiotics, the function of each biosynthetic enzyme has been extensively elucidated. The common biosynthetic intermediates 2DOS, paromamine and ribostamycin are constructed by conserved enzymes encoded in the gene clusters. The biosynthetic intermediates are then converted to characteristic architectures by unique enzymes encoded in each biosynthetic gene cluster. In this Personal Account, we summarize both common biosynthetic pathways and the pathways used for structural diversification. © 2015 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Synergy of aminoglycoside antibiotics by 3-Benzylchroman derivatives from the Chinese drug Caesalpinia sappan against clinical methicillin-resistant Staphylococcus aureus (MRSA).

    Science.gov (United States)

    Zuo, G Y; Han, Z Q; Hao, X Y; Han, J; Li, Z S; Wang, G C

    2014-06-15

    The in vitro antimicrobial activities of three 3-Benzylchroman derivatives, i.e. Brazilin (1), Brazilein (2) and Sappanone B (3) from Caesalpinia sappan L. (Leguminosae) were assayed, which mainly dealt with synergistic evaluation of aminoglycoside and other type of antibiotics against methicillin-resistant Staphylococcus aureus (MRSA) by the three compounds through the Chequerboard and Time-kill curve methods. The results showed that Compounds 1-3 alone exhibited moderate to weak activity against methicillin-susceptible S. aureus (MSSA) and other standard strains by MICs/MBCs ranged from 32/64 to >1024/>1024 μg/ml, with the order of activity as 1>2>3. Chequerboard method showed significant anti-MRSA synergy of 1/Aminoglycosides (Gentamicin, Amikacin, Etimicin and Streptomycin) combinations with (FICIs)50 at 0.375-0.5. The combined (MICs)50 values (μg/ml) reduced from 32-128/16-64 to 4-8/4-16, respectively. The percent of reduction by MICs ranged from 50% to 87.5%, with a maximum of 93.8% (1/16 of the alone MIC). Combinations of 2 and 3 with Aminoglycosides and the other antibiotics showed less potency of synergy. The dynamic Time-killing experiment further demonstrated that the combinations of 1/aminoglycoside were synergistically bactericidal against MRSA. The anti-MRSA synergy results of the bacteriostatic (Chequerboard method) and bactericidal (time-kill method) efficiencies of 1/Aminoglycoside combinations was in good consistency, which made the resistance reversed by CLSI guidelines. We concluded that the 3-Benzylchroman derivative Brazilin (1) showed in vitro synergy of bactericidal activities against MRSA when combined with Aminoglycosides, which might be beneficial for combinatory therapy of MRSA infection. Copyright © 2014. Published by Elsevier GmbH.

  6. Investigation into complexing of phthalexone S with praseodymium ions and some aminoglycoside antibiotics

    International Nuclear Information System (INIS)

    Alykov, N.M.

    1981-01-01

    Complex formation of phthalexone S (Phth) with praseodymium ion and some aminoglycoside antibiotics (Ab) in aqueous ethanol solutions (1:1) has been examined photometrically at 619 mm. It has been shown that compounds with the ratios of Ab:Pr:Phth=1:2:8, 1:1:4, 1:1:3 are formed depending on the number of amino groups and structure of the antibiotics. The molar absorptivities and solubility products for the complexes have been calculated. The complex formation scheme is given. A procedure has been developed of determining 0.01-10 μg of antibiotics in 1 ml of a biological material with a relative error of less than 10% [ru

  7. Nordihydroguaiaretic acid enhances the activities of aminoglycosides against methicillin- sensitive and resistant Staphylococcus aureus in vitro and in vivo

    Directory of Open Access Journals (Sweden)

    Edward eCunningham-Oakes

    2015-10-01

    Full Text Available Infections caused by methicillin-sensitive (MSSA and methicillin-resistant Staphylococcus aureus (MRSA are prevalent. MRSA infections are difficult to treat and there are no new classes of antibiotics produced to the market to treat infections caused by the resistant bacteria. Therefore, using antibiotic enhancers to rescue existing classes of antibiotics is an attractive strategy. Nordihydroguaiaretic acid (NDGA is an antioxidant compound found in extracts from plant Larrea Tridentata. It exhibits antimicrobial activity and may target bacterial cell membrane. Combination efficacies of NDGA with many classes of antibiotics were examined by chequerboard method against 200 clinical isolates of MRSA and MSSA. NDGA in combination with gentamicin, neomycin and tobramycin was examined by time-kill assays. The synergistic combinations of NDGA and aminoglycosides were tested in vivo using a murine skin infection model. Calculations of the fractional inhibitory concentration index (FICI showed that NDGA when combined with gentamicin, neomycin or tobramycin displayed synergistic activities in more than 97% of MSSA and MRSA, respectively. Time kill analysis demonstrated that NDGA significantly augmented the activities of these aminoglycosides against MRSA and MSSA in vitro and in murine skin infection model. The enhanced activity of NDGA resides on its ability to damage bacterial cell membrane leading to accumulation of the antibiotics inside bacterial cells. We demonstrated that NDGA strongly revived the therapeutic potencies of aminoglycosides in vitro and in vivo. This combinational strategy could contribute major clinical implications to treat antibiotic resistant bacterial infections.

  8. Mechanism of Enhanced Activity of Liposome-Entrapped Aminoglycosides against Resistant Strains of Pseudomonas aeruginosa

    Science.gov (United States)

    Mugabe, Clement; Halwani, Majed; Azghani, Ali O.; Lafrenie, Robert M.; Omri, Abdelwahab

    2006-01-01

    Pseudomonas aeruginosa is inherently resistant to most conventional antibiotics. The mechanism of resistance of this bacterium is mainly associated with the low permeability of its outer membrane to these agents. We sought to assess the bactericidal efficacy of liposome-entrapped aminoglycosides against resistant clinical strains of P. aeruginosa and to define the mechanism of liposome-bacterium interactions. Aminoglycosides were incorporated into liposomes, and the bactericidal efficacies of both free and liposomal drugs were evaluated. To define the mechanism of liposome-bacterium interactions, transmission electron microscopy (TEM), flow cytometry, lipid mixing assay, and immunocytochemistry were employed. Encapsulation of aminoglycosides into liposomes significantly increased their antibacterial activity against the resistant strains used in this study (MICs of ≥32 versus ≤8 μg/ml). TEM observations showed that liposomes interact intimately with the outer membrane of P. aeruginosa, leading to the membrane deformation. The flow cytometry and lipid mixing assays confirmed liposome-bacterial membrane fusion, which increased as a function of incubation time. The maximum fusion rate was 54.3% ± 1.5% for an antibiotic-sensitive strain of P. aeruginosa and 57.8% ± 1.9% for a drug-resistant strain. The fusion between liposomes and P. aeruginosa significantly enhanced the antibiotics' penetration into the bacterial cells (3.2 ± 2.3 versus 24.2 ± 6.2 gold particles/bacterium, P ≤ 0.001). Our data suggest that liposome-entrapped antibiotics could successfully resolve infections caused by antibiotic-resistant P. aeruginosa through an enhanced mechanism of drug entry into the bacterial cells. PMID:16723560

  9. Structural characterization of the novel aminoglycoside phosphotransferase AphVIII from Streptomyces rimosus with enzymatic activity modulated by phosphorylation

    Energy Technology Data Exchange (ETDEWEB)

    Boyko, Konstantin M., E-mail: kmb@inbi.ras.ru [Bach Institute of Biochemistry, Federal Research Centre of Biotechnology of the Russian Academy of Sciences, Leninsky Prospekt. 33, Bld. 2, 119071, Moscow (Russian Federation); National Research Center “Kurchatov Institute”, Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182 (Russian Federation); Gorbacheva, Marina A.; Korzhenevskiy, Dmitry A. [National Research Center “Kurchatov Institute”, Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182 (Russian Federation); Alekseeva, Maria G.; Mavletova, Dilara A.; Zakharevich, Natalia V.; Elizarov, Sergey M.; Rudakova, Natalia N.; Danilenko, Valery N. [Vavilov Institute of General Genetics, Russian Academy of Sciences, Gubkina str. 3, Moscow, 119333 (Russian Federation); Popov, Vladimir O. [Bach Institute of Biochemistry, Federal Research Centre of Biotechnology of the Russian Academy of Sciences, Leninsky Prospekt. 33, Bld. 2, 119071, Moscow (Russian Federation); National Research Center “Kurchatov Institute”, Kurchatov Complex of NBICS-technologies, Akad. Kurchatova sqr., 1, Moscow, 123182 (Russian Federation)

    2016-09-02

    Aminoglycoside phosphotransferases represent a broad class of enzymes that promote bacterial resistance to aminoglycoside antibiotics via the phosphorylation of hydroxyl groups in the latter. Here we report the spatial structure of the 3′-aminoglycoside phosphotransferase of novel VIII class (AphVIII) solved by X-ray diffraction method with a resolution of 2.15 Å. Deep analysis of APHVIII structure and its comparison with known structures of aminoglycoside phosphotransferases of various types reveals that AphVIII has a typical two-domain fold and, however, possesses some unique characteristics that distinguish the enzyme from its known homologues. The most important difference is the presence of the activation loop with unique Ser146 residue. We demonstrate that in the apo-state of the enzyme the activation loop does not interact with other parts of the enzyme and seems to adopt catalytically competent state only after substrate binding. - Highlights: • 3D structure of the novel aminoglycoside phosphotransferase AphVIII was obtained. • AphVIII activation loop is clearly identified in the electron density. • AphVIII has some unique structural features in its substrate C-ring binding pocket.

  10. Subcellular mechanisms involved in apoptosis induced by aminoglycoside antibiotics: Insights on p53, proteasome and endoplasmic reticulum

    International Nuclear Information System (INIS)

    Denamur, Sophie; Boland, Lidvine; Beyaert, Maxime; Verstraeten, Sandrine L.; Fillet, Marianne; Tulkens, Paul M.; Bontemps, Françoise; Mingeot-Leclercq, Marie-Paule

    2016-01-01

    Gentamicin, an aminoglycoside used to treat severe bacterial infections, may cause acute renal failure. In the renal cell line LLC-PK1, gentamicin accumulates in lysosomes, induces alterations of their permeability, and triggers the mitochondrial pathway of apoptosis via activation of caspase-9 and -3 and changes in Bcl-2 family proteins. Early ROS production in lysosomes has been associated with gentamicin induced lysosomal membrane permeabilization. In order to better understand the multiple interconnected pathways of gentamicin-induced apoptosis and ensuing renal cell toxicity, we investigated the effect of gentamicin on p53 and p21 levels. We also studied the potential effect of gentamicin on proteasome by measuring the chymotrypsin-, trypsin- and caspase-like activities, and on endoplasmic reticulum by determining phopho-eIF2α, caspase-12 activation and GRP78 and 94. We observed an increase in p53 levels, which was dependent on ROS production. Accumulation of p53 resulted in accumulation of p21 and of phospho-eIF2α. These effects could be related to an impairment of proteasome as we demonstrated an inhibition of trypsin-and caspase-like activities. Moderate endoplasmic reticulum stress could also participate to cellular toxicity induced by gentamicin, with activation of caspase-12 without change in GRP74 and GRP98. All together, these data provide new mechanistic insights into the apoptosis induced by aminoglycoside antibiotics on renal cell lines. - Highlights: • Gentamicin induces apoptosis through p53 pathway. • Gentamicin inhibits proteosomal activity. • Gentamicin activates caspase-12.

  11. Parallel pathways in the biosynthesis of aminoglycoside antibiotics [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Yi Yu

    2017-05-01

    Full Text Available Despite their inherent toxicity and the global spread of bacterial resistance, aminoglycosides (AGs, an old class of microbial drugs, remain a valuable component of the antibiotic arsenal. Recent studies have continued to reveal the fascinating biochemistry of AG biosynthesis and the rich potential in their pathway engineering. In particular, parallel pathways have been shown to be common and widespread in AG biosynthesis, highlighting nature’s ingenuity in accessing diverse natural products from a limited set of genes. In this review, we discuss the parallel biosynthetic pathways of three representative AG antibiotics—kanamycin, gentamicin, and apramycin—as well as future directions towards the discovery and development of novel AGs.

  12. Chaperonin GroEL/GroES over-expression promotes multi-drug resistance in E. coli following exposure to aminoglycoside antibiotics

    Directory of Open Access Journals (Sweden)

    Lise eGoltermann

    2016-01-01

    Full Text Available Antibiotic resistance is an increasing challenge to modern healthcare. Aminoglycoside antiobiotics cause translation corruption and protein misfolding and aggregation in Escherichia coli. We previously showed that chaperonin GroEL/GroES depletion and overexpression sensitize and promote short-term tolerance, respectively, to this drug class. Here we show that chaperonin GroEL/GroES over-expression accelerates acquisition of aminoglycoside resistance and multi-drug resistance following sub-lethal aminoglycoside antibiotic exposure. Chaperonin buffering could provide a novel mechanism for antibiotic resistance and multi-drug resistance development.

  13. Combinations of β-Lactam or Aminoglycoside Antibiotics with Plectasin Are Synergistic against Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus

    Science.gov (United States)

    Hu, Yanmin; Liu, Alexander; Vaudrey, James; Vaiciunaite, Brigita; Moigboi, Christiana; McTavish, Sharla M.; Kearns, Angela; Coates, Anthony

    2015-01-01

    Bacterial infections remain the leading killer worldwide which is worsened by the continuous emergence of antibiotic resistance. In particular, methicillin-sensitive (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) are prevalent and the latter can be difficult to treat. The traditional strategy of novel therapeutic drug development inevitably leads to emergence of resistant strains, rendering the new drugs ineffective. Therefore, rejuvenating the therapeutic potentials of existing antibiotics offers an attractive novel strategy. Plectasin, a defensin antimicrobial peptide, potentiates the activities of other antibiotics such as β-lactams, aminoglycosides and glycopeptides against MSSA and MRSA. We performed in vitro and in vivo investigations to test against genetically diverse clinical isolates of MSSA (n = 101) and MRSA (n = 115). Minimum inhibitory concentrations (MIC) were determined by the broth microdilution method. The effects of combining plectasin with β-lactams, aminoglycosides and glycopeptides were examined using the chequerboard method and time kill curves. A murine neutropenic thigh model and a murine peritoneal infection model were used to test the effect of combination in vivo. Determined by factional inhibitory concentration index (FICI), plectasin in combination with aminoglycosides (gentamicin, neomycin or amikacin) displayed synergistic effects in 76-78% of MSSA and MRSA. A similar synergistic response was observed when plectasin was combined with β-lactams (penicillin, amoxicillin or flucloxacillin) in 87–89% of MSSA and MRSA. Interestingly, no such interaction was observed when plectasin was paired with vancomycin. Time kill analysis also demonstrated significant synergistic activities when plectasin was combined with amoxicillin, gentamicin or neomycin. In the murine models, plectasin at doses as low as 8 mg/kg augmented the activities of amoxicillin and gentamicin in successful treatment of MSSA and MRSA infections. We

  14. In vitro antimicrobial activity of the aminoglycoside arbekacin tested against oxacillin-resistant Staphylococcus aureus isolated in Brazilian hospitals

    Directory of Open Access Journals (Sweden)

    Julio C. R. Cordeiro

    Full Text Available Arbekacin is an aminoglycoside used in Japan for treating infections caused by gentamicin and oxacillin-resistant S. aureus (ORSA. The objective of this study was to determine the in vitro antimicrobial activity of arbekacin against 454 clinical isolates of ORSA. The isolates were consecutively collected between January and July, 2000, from patients hospitalized in 8 Brazilian medical centers. The antimicrobial susceptibility testing was performed by disk diffusion method according to NCCLS recommendations. The vast majority of the isolates, 453 strains (99.8%, were considered susceptible to arbekacin based on the criteria proposed by the Requirements for Antibiotic Products of Japan. Only 1 isolate (0.2% was classified as resistant. On the other hand, high rates of resistance were demonstrated for other aminoglycosides, such as gentamicin (97.6% resistance and amikacin (97.0% resistance. Resistance rate was also high for ciprofloxacin (98.0%. All isolates were considered susceptible to vancomycin. The excellent in vitro antimicrobial activity of arbekacin demonstrated in this study indicates that this antimicrobial agent may play an important role in the treatment of severe ORSA infections, especially those that show poor clinical response with vancomycin monotherapy. Since the aminoglycosides should not be used as monotherapy to treat Gram positive infections, further studies evaluating in vitro and in vivo synergistic activity of arbekacin combinations are necessary to clarify the clinical role of this aminoglycoside.

  15. In vitro antimicrobial activity of the aminoglycoside arbekacin tested against oxacillin-resistant Staphylococcus aureus isolated in Brazilian hospitals

    Directory of Open Access Journals (Sweden)

    Cordeiro Julio C. R.

    2001-01-01

    Full Text Available Arbekacin is an aminoglycoside used in Japan for treating infections caused by gentamicin and oxacillin-resistant S. aureus (ORSA. The objective of this study was to determine the in vitro antimicrobial activity of arbekacin against 454 clinical isolates of ORSA. The isolates were consecutively collected between January and July, 2000, from patients hospitalized in 8 Brazilian medical centers. The antimicrobial susceptibility testing was performed by disk diffusion method according to NCCLS recommendations. The vast majority of the isolates, 453 strains (99.8%, were considered susceptible to arbekacin based on the criteria proposed by the Requirements for Antibiotic Products of Japan. Only 1 isolate (0.2% was classified as resistant. On the other hand, high rates of resistance were demonstrated for other aminoglycosides, such as gentamicin (97.6% resistance and amikacin (97.0% resistance. Resistance rate was also high for ciprofloxacin (98.0%. All isolates were considered susceptible to vancomycin. The excellent in vitro antimicrobial activity of arbekacin demonstrated in this study indicates that this antimicrobial agent may play an important role in the treatment of severe ORSA infections, especially those that show poor clinical response with vancomycin monotherapy. Since the aminoglycosides should not be used as monotherapy to treat Gram positive infections, further studies evaluating in vitro and in vivo synergistic activity of arbekacin combinations are necessary to clarify the clinical role of this aminoglycoside.

  16. Complex pollution of antibiotic resistance genes due to beta-lactam and aminoglycoside use in aquaculture farming.

    Science.gov (United States)

    Chen, Baowei; Lin, Lan; Fang, Ling; Yang, Ying; Chen, Enzhong; Yuan, Ke; Zou, Shichun; Wang, Xiaowei; Luan, Tiangang

    2018-05-01

    The prevalence of antibiotic resistance in the modern world has raised global concerns for public health. Establishing relationships between antibiotic use and antibiotic resistance genes (ARGs) is essential to understanding the dissemination and accumulation of ARGs in a human-impacted environment. In this study, ARG profiles in the sediments from a bullfrog farm, where penicillin and amoxicillin (beta-lactams) and gentamicin (aminoglycoside) were used for prophylactic purposes, were analyzed using metagenomic approaches. Analysis of both extracellular and intracellular DNA (eDNA and iDNA) demonstrated that use of the above-mentioned antibiotics led to complex pollution of ARGs not only related to beta-lactams and aminoglycoside but also to sulfonamides, tetracyclines, and macrolides. Most of the ARGs in the sediments from the bullfrog farm were likely carried by plasmids. A significant correlation was observed between the total abundance of ARG-related plasmids and that of plasmid-carrying ARGs. Approximately 85% of the plasmids likely present in the sediment from the bullfrog farm possessed at least 3 ARG subtypes, which conferred the resistance of bacterial hosts to different antibiotic categories. Our results suggest that antibiotics could lead to complex pollution of ARGs unrelated to those administered due to the concurrence of ARGs in the plasmids. Copyright © 2018. Published by Elsevier Ltd.

  17. Synthesis and Antibacterial Activity of Antibiotic-Functionalized Graphite Nanofibers

    Directory of Open Access Journals (Sweden)

    Madeline Rotella

    2015-01-01

    Full Text Available Surface functionalization of nanomaterials is an area of current investigation that supports the development of new biomaterials for applications in biology and medicine. Herein we describe the synthesis, characterization, and antibacterial properties of the first examples of antibiotic-labeled graphitic carbon nanofibers (GCNFs covalently functionalized with aminoglycoside and quinolone antibiotics. Ruthenium tetroxide oxidation of herringbone GCNFs gave higher amounts of surface carboxyl groups than previous methods. These carboxyl groups served as sites of attachment for antibiotics by acyl substitution. Bioassay of these novel, functionalized GCNFs using serial dilution and optical density methods demonstrated that antibiotic-labeled GCNFs possess significant antibacterial activity against Pseudomonas aeruginosa. The activity we observe for aminoglycoside-functionalized GCNFs suggests a membranolytic mechanism of action.

  18. Robustness analysis of culturing perturbations on Escherichia coli colony biofilm beta-lactam and aminoglycoside antibiotic tolerance

    Directory of Open Access Journals (Sweden)

    Jimenez-Taracido Lourdes

    2010-07-01

    Full Text Available Abstract Background Biofilms are ubiquitous. For instance, the majority of medical infections are thought to involve biofilms. However even after decades of investigation, the in vivo efficacy of many antimicrobial strategies is still debated suggesting there is a need for better understanding of biofilm antimicrobial tolerances. The current study's goal is to characterize the robustness of biofilm antibiotic tolerance to medically and industrially relevant culturing perturbations. By definition, robust systems will return similar, predictable responses when perturbed while non-robust systems will return very different and potentially unpredictable responses. The predictability of an antibiotic tolerance response is essential to developing, testing, and employing antimicrobial strategies. Results The antibiotic tolerance of Escherichia coli colony biofilms was tested against beta-lactam and aminoglycoside class antibiotics. Control scenario tolerances were compared to tolerances under culturing perturbations including 1 different nutritional environments 2 different temperatures 3 interruption of cellular quorum sensing and 4 different biofilm culture ages. Here, antibiotic tolerance was defined in terms of culturable biofilm cells recovered after a twenty four hour antibiotic treatment. Colony biofilm antibiotic tolerances were not robust to perturbations. Altering basic culturing parameters like nutritional environment or temperature resulted in very different, non-intuitive antibiotic tolerance responses. Some minor perturbations like increasing the glucose concentration from 0.1 to 1 g/L caused a ten million fold difference in culturable cells over a twenty four hour antibiotic treatment. Conclusions The current study presents a basis for robustness analysis of biofilm antibiotic tolerance. Biofilm antibiotic tolerance can vary in unpredictable manners based on modest changes in culturing conditions. Common antimicrobial testing methods

  19. Early transcriptional response to aminoglycoside antibiotic suggests alternate pathways leading to apoptosis of sensory hair cells in the mouse inner ear

    Directory of Open Access Journals (Sweden)

    Neil eSegil

    2015-05-01

    Full Text Available Aminoglycoside antibiotics are the drug of choice for treating many bacterial infections, but their administration results in hearing loss in nearly one fourth of the patients who receive them. Several biochemical pathways have been implicated in aminoglycoside antibiotic ototoxicity; however, little is known about how hair cells respond to aminoglycoside antibiotics at the transcriptome level. Here we have investigated the genome-wide response to the aminoglycoside antibiotic gentamicin. Using organotypic cultures of the perinatal organ of Corti, we performed RNA sequencing using cDNA libraries obtained from FACS-purified hair cells. Within 3 hours of gentamicin treatment, the messenger RNA level of more than three thousand genes in hair cells changed significantly. Bioinformatic analysis of these changes highlighted several known signal transduction pathways, including the JNK pathway and the NF-κB pathway, in addition to genes involved in the stress response, apoptosis, cell cycle control, and DNA damage repair. In contrast, only 698 genes, mainly involved in cell cycle and metabolite biosynthetic processes, were significantly affected in the non-hair cell population. The gene expression profiles of hair cells in response to gentamicin share a considerable similarity with those previously observed in gentamicin-induced nephrotoxicity. Our findings suggest that previously observed early responses to gentamicin in hair cells in specific signaling pathways are reflected in changes in gene expression. Additionally, the observed changes in gene expression of cell cycle regulatory genes indicate a disruption of the postmitotic state, which may suggest an alternative pathway regulating gentamicin-induced hair cell death. This work provides a more comprehensive view of aminoglycoside antibiotic ototoxicity, and thus contribute to identifying potential pathways or therapeutic targets to alleviate this important side effect of aminoglycoside

  20. Beneficial antimicrobial effect of the addition of an aminoglycoside to a β-lactam antibiotic in an E. coli porcine intensive care severe sepsis model.

    Science.gov (United States)

    Skorup, Paul; Maudsdotter, Lisa; Lipcsey, Miklós; Castegren, Markus; Larsson, Anders; Jonsson, Ann-Beth; Sjölin, Jan

    2014-01-01

    This study aimed to determine whether the addition of an aminoglycoside to a ß-lactam antibiotic increases the antimicrobial effect during the early phase of Gram-negative severe sepsis/septic shock. A porcine model was selected that considered each animal's individual blood bactericidal capacity. Escherichia coli, susceptible to both antibiotics, was given to healthy pigs intravenously during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either cefuroxime alone (n = 9), a combination of cefuroxime+tobramycin (n = 9), or saline (control, n = 9). Blood samples were collected hourly for cultures and quantitative polymerase chain reaction (PCR). Bacterial growth in the organs after 6 h was chosen as the primary endpoint. A blood sample was obtained at baseline before start of bacterial infusion for ex vivo investigation of the blood bactericidal capacity. At 1 h after the administration of the antibiotics, a second blood sample was taken for ex vivo investigation of the antibiotic-induced blood killing activity. All animals developed severe sepsis/septic shock. Blood cultures and PCR rapidly became negative after completed bacterial infusion. Antibiotic-induced blood killing activity was significantly greater in the combination group than in the cefuroxime group (pantibiotic groups compared with the controls (pantibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (pantibiotic-induced blood killing activity and less bacteria in the liver than cefuroxime alone. Individual blood bactericidal capacity may have a significant effect on antimicrobial outcome.

  1. Revisiting the Nucleotide and Aminoglycoside Substrate Specificity of the Bifunctional Aminoglycoside Acetyltransferase(6′)-Ie/Aminoglycoside Phosphotransferase(2″)-Ia Enzyme*

    Science.gov (United States)

    Frase, Hilary; Toth, Marta; Vakulenko, Sergei B.

    2012-01-01

    The bifunctional aminoglycoside-modifying enzyme aminoglycoside acetyltransferase(6′)-Ie/aminoglycoside phosphotransferase(2″)-Ia, or AAC(6′)-Ie/APH(2″)-Ia, is the major source of aminoglycoside resistance in Gram-positive bacterial pathogens. In previous studies, using ATP as the cosubstrate, it was reported that the APH(2″)-Ia domain of this enzyme is unique among aminoglycoside phosphotransferases, having the ability to inactivate an unusually broad spectrum of aminoglycosides, including 4,6- and 4,5-disubstituted and atypical. We recently demonstrated that GTP, and not ATP, is the preferred cosubstrate of this enzyme. We now show, using competition assays between ATP and GTP, that GTP is the exclusive phosphate donor at intracellular nucleotide levels. In light of these findings, we reevaluated the substrate profile of the phosphotransferase domain of this clinically important enzyme. Steady-state kinetic characterization using the phosphate donor GTP demonstrates that AAC(6′)-Ie/APH(2″)-Ia phosphorylates 4,6-disubstituted aminoglycosides with high efficiency (kcat/Km = 105-107 m−1 s−1). Despite this proficiency, no resistance is conferred to some of these antibiotics by the enzyme in vivo. We now show that phosphorylation of 4,5-disubstituted and atypical aminoglycosides are negligible and thus these antibiotics are not substrates. Instead, these aminoglycosides tend to stimulate an intrinsic GTPase activity of the enzyme. Taken together, our data show that the bifunctional enzyme efficiently phosphorylates only 4,6-disubstituted antibiotics; however, phosphorylation does not necessarily result in bacterial resistance. Hence, the APH(2″)-Ia domain of the bifunctional AAC(6′)-Ie/APH(2″)-Ia enzyme is a bona fide GTP-dependent kinase with a narrow substrate profile, including only 4,6-disubstituted aminoglycosides. PMID:23115238

  2. Tolerance of Norway spruce (Picea abies [L.] Karst.) embryogenic tissue to penicillin, carbapenem and aminoglycoside antibiotics

    Czech Academy of Sciences Publication Activity Database

    Malá, J.; Pavingerová, Daniela; Cvrčková, H.; Bříza, Jindřich; Dostál, J.; Šíma, P.

    2009-01-01

    Roč. 55, č. 4 (2009), s. 156-161 ISSN 1212-4834 R&D Projects: GA MZe QH71290 Institutional research plan: CEZ:AV0Z50510513 Keywords : somatic embryogenesis * Norway spruce * penicillin antibiotics * Agrobacterium tumefaciens * carbapenem antibiotics Subject RIV: EB - Genetics ; Molecular Biology

  3. RecA Inhibitors Potentiate Antibiotic Activity and Block Evolution of Antibiotic Resistance.

    Science.gov (United States)

    Alam, Md Kausar; Alhhazmi, Areej; DeCoteau, John F; Luo, Yu; Geyer, C Ronald

    2016-03-17

    Antibiotic resistance arises from the maintenance of resistance mutations or genes acquired from the acquisition of adaptive de novo mutations or the transfer of resistance genes. Antibiotic resistance is acquired in response to antibiotic therapy by activating SOS-mediated DNA repair and mutagenesis and horizontal gene transfer pathways. Initiation of the SOS pathway promotes activation of RecA, inactivation of LexA repressor, and induction of SOS genes. Here, we have identified and characterized phthalocyanine tetrasulfonic acid RecA inhibitors that block antibiotic-induced activation of the SOS response. These inhibitors potentiate the activity of bactericidal antibiotics, including members of the quinolone, β-lactam, and aminoglycoside families in both Gram-negative and Gram-positive bacteria. They reduce the ability of bacteria to acquire antibiotic resistance mutations and to transfer mobile genetic elements conferring resistance. This study highlights the advantage of including RecA inhibitors in bactericidal antibiotic therapies and provides a new strategy for prolonging antibiotic shelf life. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. Simple measurement of isepamicin, a new aminoglycoside antibiotic, in guinea pig and human plasma, using high-performance liquid chromatography with ultraviolet detection

    International Nuclear Information System (INIS)

    Dionisotti, S.; Bamonte, F.; Scaglione, F.; Ongini, E.

    1991-01-01

    Isepamicin, the 1-N-(S-alpha-hydroxy-beta-aminopropionyl) derivative of gentamicin B, is a new aminoglycoside antibiotic, which not only has most of the properties of amikacin but also is effective against several amikacin-resistant strains of bacteria. The drug was assayed in guinea-pig and human plasma with a high-performance liquid chromatographic procedure using precolumn derivatization with 1-fluoro-2,4-dinitrobenzene and ultraviolet detection. Linearity was established over the range 0.5-40 micrograms/ml using 50 microliters of plasma. Accuracy has a mean relative error of less than 3% and precision a mean coefficient of variation of 5%. Isepamicin was determined without interference from plasma constituents or other drugs commonly prescribed during aminoglycoside therapy. This procedure correlates well with radioimmunoassay and can be used either in experimental studies or therapeutic monitoring of plasma levels

  5. Simple measurement of isepamicin, a new aminoglycoside antibiotic, in guinea pig and human plasma, using high-performance liquid chromatography with ultraviolet detection

    Energy Technology Data Exchange (ETDEWEB)

    Dionisotti, S.; Bamonte, F.; Scaglione, F.; Ongini, E. (Research Lab., Schering-Plough S.P.A., Comazzo, Milan (Italy))

    1991-01-01

    Isepamicin, the 1-N-(S-alpha-hydroxy-beta-aminopropionyl) derivative of gentamicin B, is a new aminoglycoside antibiotic, which not only has most of the properties of amikacin but also is effective against several amikacin-resistant strains of bacteria. The drug was assayed in guinea-pig and human plasma with a high-performance liquid chromatographic procedure using precolumn derivatization with 1-fluoro-2,4-dinitrobenzene and ultraviolet detection. Linearity was established over the range 0.5-40 micrograms/ml using 50 microliters of plasma. Accuracy has a mean relative error of less than 3% and precision a mean coefficient of variation of 5%. Isepamicin was determined without interference from plasma constituents or other drugs commonly prescribed during aminoglycoside therapy. This procedure correlates well with radioimmunoassay and can be used either in experimental studies or therapeutic monitoring of plasma levels.

  6. Heterologous production of kasugamycin, an aminoglycoside antibiotic from Streptomyces kasugaensis, in Streptomyces lividans and Rhodococcus erythropolis L-88 by constitutive expression of the biosynthetic gene cluster.

    Science.gov (United States)

    Kasuga, Kano; Sasaki, Akira; Matsuo, Takashi; Yamamoto, Chika; Minato, Yuiko; Kuwahara, Naoya; Fujii, Chikako; Kobayashi, Masayuki; Agematu, Hitosi; Tamura, Tomohiro; Komatsu, Mamoru; Ishikawa, Jun; Ikeda, Haruo; Kojima, Ikuo

    2017-05-01

    Kasugamycin (KSM), an aminoglycoside antibiotic isolated from Streptomyces kasugaensis cultures, has been used against rice blast disease for more than 50 years. We cloned the KSM biosynthetic gene (KBG) cluster from S. kasugaensis MB273-C4 and constructed three KBG cassettes (i.e., cassettes I-III) to enable heterologous production of KSM in many actinomycetes by constitutive expression of KBGs. Cassette I comprised all putative transcriptional units in the cluster, but it was placed under the control of the P neo promoter from Tn5. It was not maintained stably in Streptomyces lividans and did not transform Rhodococcus erythropolis. Cassette II retained the original arrangement of KBGs, except that the promoter of kasT, the specific activator gene for KBG, was replaced with P rpsJ , the constitutive promoter of rpsJ from Streptomyces avermitilis. To enhance the intracellular concentration of myo-inositol, an expression cassette of ino1 encoding the inositol-1-phosphate synthase from S. avermitilis was inserted into cassette II to generate cassette III. These two cassettes showed stable maintenance in S. lividans and R. erythropolis to produce KSM. Particularly, the transformants of S. lividans induced KSM production up to the same levels as those produced by S. kasugaensis. Furthermore, cassette III induced more KSM accumulation than cassette II in R. erythropolis, suggesting an exogenous supply of myo-inositol by the ino1 expression in the host. Cassettes II and III appear to be useful for heterologous KSM production in actinomycetes. Rhodococcus exhibiting a spherical form in liquid cultivation is also a promising heterologous host for antibiotic fermentation.

  7. In vitro bactericidal activity of aminoglycosides, including the next-generation drug plazomicin, against Brucella spp.

    Science.gov (United States)

    Plazomicin is a next-generation aminoglycoside with a potentially improved safety profile compared to other aminoglycosides. This study assessed plazomicin MICs and MBCs in four Brucella spp. reference strains. Like other aminoglycosides and aminocyclitols, plazomicin MBC values equaled MIC values ...

  8. EPR studies of free radicals decay and survival in gamma irradiated aminoglycoside antibiotics: sisomicin, tobramycin and paromomycin.

    Science.gov (United States)

    Wilczyński, Sławomir; Pilawa, Barbara; Koprowski, Robert; Wróbel, Zygmunt; Ptaszkiewicz, Marta; Swakoń, Jan; Olko, Paweł

    2012-02-14

    Radiation sterilization technology is more actively used now that any time because of its many advantages. Gamma radiation has high penetrating power, relatively low chemical reactivity and causes small temperature rise. But on the other hand radiosterilization can lead to radiolytic products appearing, in example free radicals. Free radicals in radiative sterilized sisomicin, tobramycin and paromomycin were studied by electron paramagnetic resonance (EPR) spectroscopy. Dose of gamma irradiation of 25kGy was used. Concentrations and properties of free radicals in irradiated antibiotics were studied. EPR spectra were recorded for samples stored in air and argon. For gamma irradiated antibiotics strong EPR lines were recorded. One- and two-exponential functions were fitted to experimental points during testing and researching of time influence of the antibiotics storage to studied parameters of EPR lines. Our study of free radicals in radiosterilized antibiotics indicates the need for characterization of medicinal substances prior to sterilization process using EPR values. We propose the concentration of free radicals and other spectroscopic parameters as useful factors to select the optimal type of sterilization for the individual drug. The important parameters are i.a. the τ time constants and K constants of exponential functions. Time constants τ give us information about the speed of free radicals concentration decrease in radiated medicinal substances. The constant K(0) shows the free radicals concentration in irradiated medicament after long time of storage. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Mutational activation of the AmgRS two-component system in aminoglycoside-resistant Pseudomonas aeruginosa.

    Science.gov (United States)

    Lau, Calvin Ho-Fung; Fraud, Sebastien; Jones, Marcus; Peterson, Scott N; Poole, Keith

    2013-05-01

    The amgRS operon encodes a presumed membrane stress-responsive two-component system linked to intrinsic aminoglycoside resistance in Pseudomonas aeruginosa. Genome sequencing of a lab isolate showing modest pan-aminoglycoside resistance, strain K2979, revealed a number of mutations, including a substitution in amgS that produced an R182C change in the AmgS sensor kinase product of this gene. Introduction of this mutation into an otherwise wild-type strain recapitulated the resistance phenotype, while correcting the mutation in the resistant mutant abrogated the resistant phenotype, confirming that the amgS mutation is responsible for the aminoglycoside resistance of strain K2979. The amgSR182 mutation promoted an AmgR-dependent, 2- to 3-fold increase in expression of the AmgRS target genes htpX and PA5528, mirroring the impact of aminoglycoside exposure of wild-type cells on htpX and PA5528 expression. This suggests that amgSR182 is a gain-of-function mutation that activates AmgS and the AmgRS two-component system in promoting modest resistance to aminoglycosides. Screening of several pan-aminoglycoside-resistant clinical isolates of P. aeruginosa revealed three that showed elevated htpX and PA5528 expression and harbored single amino acid-altering mutations in amgS (V121G or D106N) and no mutations in amgR. Introduction of the amgSV121G mutation into wild-type P. aeruginosa generated a resistance phenotype reminiscent of the amgSR182 mutant and produced a 2- to 3-fold increase in htpX and PA5528 expression, confirming that it, too, is a gain-of-function aminoglycoside resistance-promoting mutation. These results highlight the contribution of amgS mutations and activation of the AmgRS two-component system to acquired aminoglycoside resistance in lab and clinical isolates of P. aeruginosa.

  10. A rapid SPE-based analytical method for UPLC/MS/MS determination of aminoglycoside antibiotic residues in bovine milk, muscle, and kidney.

    Science.gov (United States)

    Young, Michael S; van Tran, Kim; Goh, Evelyn; Shia, Jeremy C

    2014-01-01

    An SPE-based cleanup protocol was developed for ultra-performance LC (UPLC)/MS/MS determination of residues of the common aminoglycoside antibiotics streptomycin, dihydrostreptomycin, neomycin, and gentamicin in bovine milk, kidney, and muscle. Recoveries for all compounds except neomycin ranged from 80 to 104% for all matrixes studied; recoveries for neomycin ranged from 71 to 84%. Intraday and interday precision data were under 15% for all sample matrixes. Compared with other recently reported cleanup methods, less sample is required, the use of potentially dangerous reagents is minimized, and fewer manipulations are required by the analyst. A high throughput 96-well plate format was used for SPE cleanup and UPLC/MS analysis.

  11. Evaluation on the Use of β-Lactamase and Aminoglycoside Modifying Enzyme Gene Sequences as Markers for the Early Detection of Antibiotic Resistance Profile of Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Victor A. Doss

    2004-01-01

    Full Text Available Pseudomonas aeruginosa is one of the major causes of infections including the hospital acquired (Nosocomial infections. Detection of them and their antibiotic resistance profile by conventional method takes about three days. Recently, DNA based diagnostic methods are being used for the identification of the pathogens. Hence we have tested a rapid and sensitive method using DNA sequences as markers for detecting the presence of three genes coding for the enzymes that inactivate the two most commonly used Anti-pseudomonadal drugs such as β-lactam antibiotics (Penicillin, and its derivatives and Aminoglycosides such as Gentamicin, Tobramycin, Amikacin, Streptomycin. The internal region of these genes were used for designing and synthesizing primers and these primers were used in Polymerase Chain Reaction (PCR to screen for the presence of these genes in the clinical isolates and to label them non-radioactively with Biotin. They in turn were used to detect the presence of the antibiotic resistance genes in the clinical isolates by hybridization. The specificity (ratio of positive results obtained in both methods and the sensitivity (the minimum amount of sample DNA and the labeled probe required for the tests were evaluated.

  12. Aminoglycoside induced ototoxicity associated with mitochondrial ...

    African Journals Online (AJOL)

    . Joseph Foster II, Mustafa Tekin. Abstract. Despite the risk of permanent ototoxic effects, aminoglycosides remain commonly utilized antibiotics worldwide due to low cost and efficiency in treating severe infections. Over the last two decades, ...

  13. tmRNA decreases the bactericidal activity of aminoglycosides and the susceptibility to inhibitors of cell wall synthesis.

    Science.gov (United States)

    Luidalepp, Hannes; Hallier, Marc; Felden, Brice; Tenson, Tanel

    2005-04-01

    Trans-translation is a process that recycles ribosomes stalled on problematic mRNAs. tmRNA, coded by the DeltassrA gene, is a major component of trans-translation. Bacteria lacking tmRNA are more sensitive to several inhibitors of protein synthesis when compared to a wild type strain. We measured bacterial growth of the DeltassrA and wild type strains in Escherichia coli in the presence of 14 antibiotics including some that do not target protein synthesis. Both the optical density of the bacterial cultures and the number of viable cells were monitored. For the ribosome-targeted antibiotics, sensitization was observed on erythromycin, chloramphenicol, kanamycin, puromycin and streptomycin. Minor or no effects were observed with clindamycin, tetracycline and spectinomycin. Surprisingly, the DeltassrA strain is more sensitive than wild type to inhibitors of cell wall synthesis: fosfomycin and ampicillin. No growth difference was observed on drugs with other target sites: ofloxacin, norfloxacin, rifampicin and trimethoprim. Sensitization to antibiotics having target sites other than the ribosome suggests that trans-translation could influence antibiotic-induced stress responses. In trans-translation-deficient bacteria, cell death is significantly enhanced by the two aminoglycosides that induce translational misreading, streptomycin and kanamycin.

  14. Real-time examination of aminoglycoside activity towards bacterial mimetic membranes using Quartz Crystal Microbalance with Dissipation monitoring (QCM-D).

    Science.gov (United States)

    Joshi, Tanmaya; Voo, Zhi Xiang; Graham, Bim; Spiccia, Leone; Martin, Lisandra L

    2015-02-01

    The rapid increase in multi-drug resistant bacteria has resulted in previously discontinued treatments being revisited. Aminoglycosides are effective "old" antibacterial agents that fall within this category. Despite extensive usage and understanding of their intracellular targets, there is limited mechanistic knowledge regarding how aminoglycosides penetrate bacterial membranes. Thus, the activity of two well-known aminoglycosides, kanamycin A and neomycin B, towards a bacterial mimetic membrane (DMPC:DMPG (4:1)) was examined using a Quartz Crystal Microbalance with Dissipation monitoring (QCM-D). The macroscopic effect of increasing the aminoglycoside concentration showed that kanamycin A exerts a threshold response, switching from binding to the membrane to disruption of the surface. Neomycin B, however, disrupted the membrane at all concentrations examined. At concentrations above the threshold value observed for kanamycin A, both aminoglycosides revealed similar mechanistic details. That is, they both inserted into the bacterial mimetic lipid bilayer, prior to disruption via loss of materials, presumably aminoglycoside-membrane composites. Depth profile analysis of this membrane interaction was achieved using the overtones of the quartz crystal sensor. The measured data is consistent with a two-stage process in which insertion of the aminoglycoside precedes the 'detergent-like' removal of membranes from the sensor. The results of this study contribute to the insight required for aminoglycosides to be reconsidered as active antimicrobial agents/co-agents by providing details of activity at the bacterial membrane. Kanamycin and neomycin still offer potential as antimicrobial therapeutics for the future and the QCM-D method illustrates great promise for screening new antibacterial or antiviral drug candidates. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Herbal therapy associated with antibiotic therapy: potentiation of the antibiotic activity against methicillin – resistant Staphylococcus aureus by Turnera ulmifolia L

    Directory of Open Access Journals (Sweden)

    Lima Edeltrudes O

    2009-05-01

    Full Text Available Abstract Background Staphylococcus genus is widely spread in nature being part of the indigenous microbiota of skin and mucosa of animal and birds. Some Staphylococcus species are frequently recognized as etiological agents of many animal and human opportunistic infections This is the first report testing the antibiotic resistance-modifying activity of Turnera ulmifolia against methicillin-resistant Staphylococcus aureus – MRSA strain. Methods In this study an ethanol extract of Turnera ulmifolia L. and chlorpromazine were tested for their antimicrobial activity alone or in combination with aminoglycosides against an MRSA strain. Results The synergism of the ethanol extract and aminoglycosides were verified using microdillution method. A synergistic effect of this extract on gentamicin and kanamycin was demonstrated. Similarly, a potentiating effect of chlorpromazine on kanamycin, gentamicin and neomycin, indicating the involvement of an efflux system in the resistance to these aminoglycosides. Conclusion It is therefore suggested that extracts from Turnera ulmifolia could be used as a source of plant-derived natural products with resistance-modifying activity, constituting a new weapon against the problem of bacterial resistance to antibiotics demonstrated in MRSA strains.

  16. Antibacterial, modulatory activity of antibiotics and toxicity from Rhinella jimi (Stevaux, 2002) (Anura: Bufonidae) glandular secretions.

    Science.gov (United States)

    Sales, Débora Lima; Morais-Braga, Maria Flaviana Bezerra; Santos, Antonia Thassya Lucas Dos; Machado, Antonio Judson Targino; Araujo Filho, João Antonio de; Dias, Diógenes de Queiroz; Cunha, Francisco Assis Bezerra da; Saraiva, Rogério de Aquino; Menezes, Irwin Rose Alencar de; Coutinho, Henrique Douglas Melo; Costa, José Galberto Martins; Ferreira, Felipe Silva; Alves, Rômulo Romeu da Nóbrega; Almeida, Waltécio de Oliveira

    2017-08-01

    The increase in microorganisms with resistance to medications has caused a strong preoccupation within the medical and scientific community. Animal toxins studies, such as parotoid glandular secretions from amphibians, possesses a great potential in the development of drugs, such as antimicrobials, as these possess bioactive compounds. It was evaluated Rhinella jimi (Stevaux, 2002) glandular secretions against standard and multi-resistant bacterial strains; the effect of secretions combined with drugs; and determined the toxicity using two biologic in vivo models, and a in vitro model with mice livers. Standard strains were used for the determination of the Minimum Inhibitory Concentration (MIC), while for the modulatory activity of antibiotics, the clinical isolates Escherichia coli 06, Pseudomonas aeruginosa 03 and Staphylococcus aureus 10 were used. Modulatory activity was evaluated by the broth microdilution method with aminoglycosides and β-lactams as target antibiotics. The secretions in association with the antibiotics have a significant reduction in MIC, both the aminoglycosides and β-lactams. The toxicity and cytotoxicity results were lower than the values used in the modulation. R. jimi glandular secretions demonstrated clinically relevant results regarding the modulation of the tested antimicrobials. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  17. In vitro activity of aminoglycosides against clinical isolates of Acinetobacter baumannii complex and other nonfermentative Gram-negative bacilli causing healthcare-associated bloodstream infections in Taiwan.

    Science.gov (United States)

    Liu, Jyh-You; Wang, Fu-Der; Ho, Mao-Wang; Lee, Chen-Hsiang; Liu, Jien-Wei; Wang, Jann-Tay; Sheng, Wang-Huei; Hseuh, Po-Ren; Chang, Shan-Chwen

    2016-12-01

    Aminoglycosides possess in vitro activity against aerobic and facultative Gram-negative bacilli. However, nationwide surveillance on susceptibility data of Acinetobacter baumannii complex and Pseudomonas aeruginosa to aminoglycosides was limited, and aminoglycoside resistance has emerged in the past decade. We study the in vitro susceptibility of A. baumannii complex and other nonfermentative Gram-negative bacilli (NFGNB) to aminoglycosides. A total of 378 NFGNB blood isolates causing healthcare-associated bloodstream infections during 2008 and 2013 at four medical centers in Taiwan were tested for their susceptibilities to four aminoglycosides using the agar dilution method (gentamicin, amikacin, tobramycin, and isepamicin) and disc diffusion method (isepamicin). A. baumannii was highly resistant to all four aminoglycosides (range of susceptibility, 0-4%), whereas >80% of Acinetobacter nosocomialis and Acinetobacter pittii blood isolates were susceptible to amikacin (susceptibility: 96% and 91%, respectively), tobramycin (susceptibility: 92% and 80%, respectively), and isepamicin (susceptibility: 96% and 80%, respectively). All aminoglycosides except gentamicin possessed good in vitro activity (>94%) against P. aeruginosa. Amikacin has the best in vitro activity against P. aeruginosa (susceptibility, 98%), followed by A. nosocomialis (96%), and A. pittii (91%), whereas tobramycin and isepamicin were less potent against A. pittii (both 80%). Aminoglycoside resistances were prevalent in Stenotrophomonas maltophilia and Burkholderia cepacia complex blood isolates in Taiwan. Genospecies among the A. baumannii complex had heterogeneous susceptibility profiles to aminoglycosides. Aminoglycosides, except gentamicin, remained good in vitro antimicrobial activity against P. aeruginosa. Further in vivo clinical data and continuous resistance monitoring are warranted for clinical practice guidance. Copyright © 2015. Published by Elsevier B.V.

  18. Triclosan-Induced Aminoglycoside-Tolerant Listeria monocytogenes Isolates Can Appear as Small-Colony Variants

    DEFF Research Database (Denmark)

    Kastbjerg, Vicky Gaedt; Hein-Kristensen, Line; Gram, Lone

    2014-01-01

    Exposure of the human food-borne pathogen Listeria monocytogenes to sublethal concentrations of triclosan can cause resistance to several aminoglycosides. Aminoglycoside-resistant isolates exhibit two colony morphologies: normal-size and pinpoint colonies. The purposes of the present study were...... to characterize the small colonies of L. monocytogenes and to determine if specific genetic changes could explain the triclosan-induced aminoglycoside resistance in both pinpoint and normal-size isolates. Isolates from the pinpoint colonies grew poorly under aerated conditions, but growth was restored by addition......I and that exposure to triclosan can cause resistance to antibiotics that enters the cell via active transport. Further studies are needed to elucidate if L. monocytogenes pinpoint isolates could have any clinical impact, e.g., in persistent infections....

  19. Aminoglycoside Concentrations Required for Synergy with Carbapenems against Pseudomonas aeruginosa Determined via Mechanistic Studies and Modeling.

    Science.gov (United States)

    Yadav, Rajbharan; Bulitta, Jürgen B; Schneider, Elena K; Shin, Beom Soo; Velkov, Tony; Nation, Roger L; Landersdorfer, Cornelia B

    2017-12-01

    This study aimed to systematically identify the aminoglycoside concentrations required for synergy with a carbapenem and characterize the permeabilizing effect of aminoglycosides on the outer membrane of Pseudomonas aeruginosa Monotherapies and combinations of four aminoglycosides and three carbapenems were studied for activity against P. aeruginosa strain AH298-GFP in 48-h static-concentration time-kill studies (SCTK) (inoculum: 10 7.6 CFU/ml). The outer membrane-permeabilizing effect of tobramycin alone and in combination with imipenem was characterized via electron microscopy, confocal imaging, and the nitrocefin assay. A mechanism-based model (MBM) was developed to simultaneously describe the time course of bacterial killing and prevention of regrowth by imipenem combined with each of the four aminoglycosides. Notably, 0.25 mg/liter of tobramycin, which was inactive in monotherapy, achieved synergy (i.e., ≥2-log 10 more killing than the most active monotherapy at 24 h) combined with imipenem. Electron micrographs, confocal image analyses, and the nitrocefin uptake data showed distinct outer membrane damage by tobramycin, which was more extensive for the combination with imipenem. The MBM indicated that aminoglycosides enhanced the imipenem target site concentration up to 4.27-fold. Tobramycin was the most potent aminoglycoside to permeabilize the outer membrane; tobramycin (0.216 mg/liter), gentamicin (0.739 mg/liter), amikacin (1.70 mg/liter), or streptomycin (5.19 mg/liter) was required for half-maximal permeabilization. In summary, our SCTK, mechanistic studies and MBM indicated that tobramycin was highly synergistic and displayed the maximum outer membrane disruption potential among the tested aminoglycosides. These findings support the optimization of highly promising antibiotic combination dosage regimens for critically ill patients. Copyright © 2017 American Society for Microbiology.

  20. Meropenem potentiation of aminoglycoside activity against Pseudomonas aeruginosa: involvement of the MexXY-OprM multidrug efflux system.

    Science.gov (United States)

    Poole, Keith; Gilmour, Christie; Farha, Maya A; Parkins, Michael D; Klinoski, Rachael; Brown, Eric D

    2018-02-06

    To assess the ability of meropenem to potentiate aminoglycoside (AG) activity against laboratory and AG-resistant cystic fibrosis (CF) isolates of Pseudomonas aeruginosa and to elucidate its mechanism of action. AG resistance gene deletions were engineered into P. aeruginosa laboratory and CF isolates using standard gene replacement technology. Susceptibility to AGs ± meropenem (at ½ MIC) was assessed using a serial 2-fold dilution assay. mexXY expression and MexXY-OprM efflux activity were quantified using quantitative PCR and an ethidium bromide accumulation assay, respectively. A screen for agents that rendered WT P. aeruginosa susceptible to a sub-MIC concentration of the AG paromomycin identified the carbapenem meropenem, which potentiated several additional AGs. Meropenem potentiation of AG activity was largely lost in a mutant lacking the MexXY-OprM multidrug efflux system, an indication that it was targeting this efflux system in enhancing P. aeruginosa susceptibility to AGs. Meropenem failed to block AG induction of mexXY expression or MexXY-OprM efflux activity, suggesting that it may be interfering with some MexXY-dependent process linked to AG susceptibility. Meropenem potentiated AG activity versus AG-resistant CF isolates, enhancing susceptibility to at least one AG in all isolates and susceptibility to all tested AGs in 50% of the isolates. Notably, meropenem potentiation of AG activity was linked to MexXY in some but not all CF isolates in which this was examined. Meropenem potentiates AG activity against laboratory and CF strains of P. aeruginosa, both dependent on and independent of MexXY, highlighting the complexity of AG resistance in this organism. © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. AMINOGLYCOSIDE RESISTANCE GENES IN Pseudomonas aeruginosa ISOLATES FROM CUMANA, VENEZUELA.

    Science.gov (United States)

    Teixeira, Bertinellys; Rodulfo, Hectorina; Carreño, Numirin; Guzmán, Militza; Salazar, Elsa; De Donato, Marcos

    2016-01-01

    The enzymatic modification of aminoglycosides by aminoglycoside-acetyltransferases (AAC), aminoglycoside-adenyltransferases (AAD), and aminoglycoside-phosphotransferases (APH), is the most common resistance mechanism in P. aeruginosa and these enzymes can be coded on mobile genetic elements that contribute to their dispersion. One hundred and thirty seven P. aeruginosa isolates from the University Hospital, Cumana, Venezuela (HUAPA) were evaluated. Antimicrobial susceptibility was determined by the disk diffusion method and theaac, aadB and aph genes were detected by PCR. Most of the P. aeruginosa isolates (33/137) were identified from the Intensive Care Unit (ICU), mainly from discharges (96/137). The frequency of resistant P. aeruginosaisolates was found to be higher for the aminoglycosides tobramycin and amikacin (30.7 and 29.9%, respectively). Phenotype VI, resistant to these antibiotics, was the most frequent (14/49), followed by phenotype I, resistant to all the aminoglycosides tested (12/49). The aac(6´)-Ib,aphA1 and aadB genes were the most frequently detected, and the simultaneous presence of several resistance genes in the same isolate was demonstrated. Aminoglycoside resistance in isolates ofP. aeruginosa at the HUAPA is partly due to the presence of the aac(6´)-Ib, aphA1 andaadB genes, but the high rates of antimicrobial resistance suggest the existence of several mechanisms acting together. This is the first report of aminoglycoside resistance genes in Venezuela and one of the few in Latin America.

  2. Antibiotic rezistance genes in soil actinobacteria

    OpenAIRE

    Patrmanová, Tereza

    2016-01-01

    Actinobacteria are important members of the soil ecosystems, where they are involved in organic matter decomposition. It is worth mentioning that their secondary metabolism allows them to produce a variety of different compounds. These compounds include antibiotics, among them aminoglycosides have a place in clinical practice. These antibiotics are significant due to a broad spectrum of activities against both gram-negative and gram-positive bacteria. However, their use currently carries a ri...

  3. Triclosan-Induced Aminoglycoside-Tolerant Listeria monocytogenes Isolates Can Appear as Small-Colony Variants

    Science.gov (United States)

    Kastbjerg, Vicky G.; Hein-Kristensen, Line

    2014-01-01

    Exposure of the human food-borne pathogen Listeria monocytogenes to sublethal concentrations of triclosan can cause resistance to several aminoglycosides. Aminoglycoside-resistant isolates exhibit two colony morphologies: normal-size and pinpoint colonies. The purposes of the present study were to characterize the small colonies of L. monocytogenes and to determine if specific genetic changes could explain the triclosan-induced aminoglycoside resistance in both pinpoint and normal-size isolates. Isolates from the pinpoint colonies grew poorly under aerated conditions, but growth was restored by addition of antibiotics. Pinpoint isolates had decreased hemolytic activity under stagnant conditions and a changed spectrum of carbohydrate utilization compared to the wild type and isolates from normal-size colonies. Genome sequence comparison revealed that all seven pinpoint isolates had a mutation in a heme gene, and addition of heme caused the pinpoint isolates to revert to normal colony size. Triclosan-induced gentamicin-resistant isolates had mutations in several different genes, and it cannot be directly concluded how the different mutations caused gentamicin resistance. However, since many of the mutations affected proteins involved in respiration, it seems likely that the mutations affected the active transport of the antibiotic and thereby caused resistance by decreasing the amount of aminoglycoside that enters the bacterial cell. Our study emphasizes that triclosan likely has more targets than just fabI and that exposure to triclosan can cause resistance to antibiotics that enters the cell via active transport. Further studies are needed to elucidate if L. monocytogenes pinpoint isolates could have any clinical impact, e.g., in persistent infections. PMID:24637686

  4. Analysis of Aminoglycoside Modifying Enzyme Genes Responsible for High-Level Aminoglycoside Resistance among Enterococcal Isolates

    Directory of Open Access Journals (Sweden)

    Vishal Shete

    2017-01-01

    Full Text Available Enzymatic modification results in high-level resistance to aminoglycoside (HLAR, which eliminates the synergistic bactericidal effect of combined exposure to a cell wall-active agent and an aminoglycoside. So aim of the study was to determine prevalence of HLAR enterococcal isolate and to study distribution of aminoglycoside modifying enzyme genes in them. A total of 100 nonrepeat isolates of enterococci from various clinical samples were analyzed. As per Clinical and Laboratory Standards Institute guidelines enterococci were screened for HLAR by Kirby-Bauer disc diffusion method. Minimum inhibitory concentration of all isolates for gentamicin and streptomycin was determined by E-test. Multiplex polymerase chain reaction (PCR was carried out for HLAR enterococcal isolates to identify aminoglycoside modifying enzymes genes responsible for resistance. 60% isolates were found to be high-level gentamicin resistant (HLGR whereas 45% isolates were found to be high-level streptomycin resistant (HLSR. By multiplex PCR 80% HLGR isolates carried bifunctional aminoglycoside modifying enzyme gene aac(6′-Ie-aph(2′′-Ia whereas 18 out of 45 high-level streptomycin resistant, that is, 40%, isolates carried aph(3′-IIIa. However, aph(2′′-Ib, aph(2′′-Ic, aph(2′′-Id, and ant(4′-Ia genes which encode other aminoglycosides modifying enzymes were not detected. Bifunctional aminoglycoside modifying enzyme gene aac(6′-Ie-aph(2′′-Ia is the predominant gene responsible for HLAR.

  5. 21 CFR 333.110 - First aid antibiotic active ingredients.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 false First aid antibiotic active ingredients. 333.110... (CONTINUED) DRUGS FOR HUMAN USE TOPICAL ANTIMICROBIAL DRUG PRODUCTS FOR OVER-THE-COUNTER HUMAN USE First Aid Antibiotic Drug Products § 333.110 First aid antibiotic active ingredients. The product consists of any of...

  6. Kinetic and mutagenic characterization of the chromosomally encoded Salmonella enterica AAC(6')-Iy aminoglycoside N-acetyltransferase.

    Science.gov (United States)

    Magnet, S; Lambert, T; Courvalin, P; Blanchard, J S

    2001-03-27

    The chromosomally encoded aminoglycoside N-acetyltransferase, AAC(6')-Iy, from Salmonella enterica confers resistance toward a number of aminoglycoside antibiotics. The structural gene was cloned and expressed and the purified enzyme existed in solution as a dimer of ca. 17 000 Da monomers. Acetyl-CoA was the preferred acyl donor, and most therapeutically important aminoglycosides were substrates for acetylation. Exceptions are those aminoglycosides that possess a 6'-hydroxyl substituent (e.g., lividomycin). Thus, the enzyme exhibited regioselective and exclusive acetyltransferase activity to 6'-amine-containing aminoglycosides. The enzyme exhibited Michaelis-Menten kinetics for some aminoglycoside substrates but "substrate activation" with others. Kinetic studies supported a random kinetic mechanism for the enzyme. The enzyme was inactivated by iodoacetamide in a biphasic manner, with half of the activity being lost rapidly and the other half more slowly. Tobramycin, but not acetyl-CoA, protected against inactivation. Each of the three cysteine residues (C70, C109, C145) in the wild-type enzyme were carboxamidomethylated by iodoacetamide. Cysteine 109 in AAC(6')-Iy is conserved in 12 AAC(6') enzyme sequences of the major class I subfamily. Surprisingly, mutation of this residue to alanine neither abolished activity nor altered the biphasic inactivation by iodoacetamide. The maximum velocity and V/K values for a number of aminoglycosides were elevated in this single mutant, and the kinetic behavior of substrates exhibiting linear vs nonlinear kinetics was reversed. Cysteine 70 in AAC(6')-Iy is either a cysteine or a threonine residue in all 12 AAC(6') enzymes of the major class I subfamily. The double mutant, C109A/C70A, was not inactivated by iodoacetamide. The double mutant exhibited large increases in the K(m) values for both acetyl-CoA and aminoglycoside substrates, and all aminoglycoside substrates exhibited Michaelis-Menten kinetics. Solvent kinetic isotope

  7. Methods for chemical synthesis of biologically active compounds using supramolecular protective groups and novel compounds obtainable Thereby

    NARCIS (Netherlands)

    Herrmann, Andreas; Bastian, Andreas Alexander; Marcozzi, Alessio

    2014-01-01

    The invention relates to drug development and synthetic chemistry, in particular to the manufacture of biologically active compounds based on naturally occurring molecules. It also relates to novel biologically active compounds, for example aminoglycoside antibiotics, in a substantially pure

  8. Intracellular polyamine pools, oligopeptide-binding protein A expression, and resistance to aminoglycosides in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Maria BR Acosta

    2005-11-01

    Full Text Available The role of intracellular free polyamine (putrescine and spermidine pools in multiple resistance to aminoglycoside antibiotics was investigated among in vitro selected kanamycin-resistant Escherichia coli J53 mutants expressing diminished oligopeptide-binding protein (OppA levels and/or defective ornithine decarboxylase (ODC activity. The results suggest that diminished OppA content, but not defective ODC activity expression, increased the relative concentration of free spermidine as compared to the wild type strain. Moreover, by adding exogenous polyamines or polyamine synthesis inhibitors to cultures with different mutant strains, a direct relationship between the intracellular OppA levels and resistance to kanamycin was revealed. Collectively these results further suggest a complex relation among OppA expression, aminoglycoside resistance and polyamine metabolism.

  9. Aminoglycoside resistance profile and structural architecture of the aminoglycoside acetyltransferase AAC(6')-Im.

    Science.gov (United States)

    Smith, Clyde A; Bhattacharya, Monolekha; Toth, Marta; Stewart, Nichole K; Vakulenko, Sergei B

    2017-11-09

    Aminoglycoside 6'-acetyltransferase-Im (AAC(6')-Im) is the closest monofunctional homolog of the AAC(6')-Ie acetyltransferase of the bifunctional enzyme AAC(6')-Ie/APH(2")-Ia. The AAC(6')-Im acetyltransferase confers 4- to 64-fold higher MICs to 4,6-disubstituted aminoglycosides and the 4,5-disubstituted aminoglycoside neomycin than AAC(6')-Ie, yet unlike AAC(6')-Ie, the AAC(6')-Im enzyme does not confer resistance to the atypical aminoglycoside fortimicin. The structure of the kanamycin A complex of AAC(6')-Im shows that the substrate binds in a shallow positively-charged pocket, with the N6' amino group positioned appropriately for an efficient nucleophilic attack on an acetyl-CoA cofactor. The AAC(6')-Ie enzyme binds kanamycin A in a sufficiently different manner to position the N6' group less efficiently, thereby reducing the activity of this enzyme towards the 4,6-disubstituted aminoglycosides. Conversely, docking studies with fortimicin in both acetyltransferases suggest that the atypical aminoglycoside might bind less productively in AAC(6')-Im, thus explaining the lack of resistance to this molecule.

  10. Antibiotics

    Science.gov (United States)

    Antibiotics are powerful medicines that fight bacterial infections. Used properly, antibiotics can save lives. They either kill bacteria or ... natural defenses can usually take it from there. Antibiotics do not fight infections caused by viruses, such ...

  11. Impact of chlortetracycline and sulfapyridine antibiotics on soil enzyme activities

    Science.gov (United States)

    Molaei, Ali; Lakzian, Amir; Datta, Rahul; Haghnia, Gholamhosain; Astaraei, Alireza; Rasouli-Sadaghiani, MirHassan; Ceccherini, Maria T.

    2017-10-01

    Pharmaceutical antibiotics are frequently used in the livestock and poultry industries to control infectious diseases. Due to the lack of proper guidance for use, the majority of administrated antibiotics and their metabolites are excreted to the soil environment through urine and feces. In the present study, we used chlortetracycline and sulfapyridine antibiotics to screen out their effects on dehydrogenase, alkaline phosphatase and urease activity. Factorial experiments were conducted with different concentrations of antibiotic (0, 10, 25 and 100 mg kg-1 of soil) mixed with soil samples, and the enzyme activity was measured at intervals of 1, 4 and 21 days. The results show that the chlortetracycline and sulfapyridine antibiotics negatively affect the dehydrogenase activity, but the effect of sulfapyridine decreases with time of incubation. Indeed, sulfapyridine antibiotic significantly affect the alkaline phosphatase activity for the entire three-time interval, while chlortetracycline seems to inhibit its activity within 1 and 4 days of incubation. The effects of chlortetracycline and sulfapyridine antibiotics on urease activity appear similar, as they both significantly affect the urease activity on day 1 of incubation. The present study concludes that chlortetracycline and sulfapyridine antibiotics have harmful effects on soil microbes, with the extent of effects varying with the duration of incubation and the type of antibiotics used.

  12. AMINOGLYCOSIDE RESISTANCE GENES IN Pseudomonas aeruginosa ISOLATES FROM CUMANA, VENEZUELA

    Directory of Open Access Journals (Sweden)

    Bertinellys TEIXEIRA

    2016-01-01

    Full Text Available The enzymatic modification of aminoglycosides by aminoglycoside-acetyltransferases (AAC, aminoglycoside-adenyltransferases (AAD, and aminoglycoside-phosphotransferases (APH, is the most common resistance mechanism in P. aeruginosa and these enzymes can be coded on mobile genetic elements that contribute to their dispersion. One hundred and thirty seven P. aeruginosa isolates from the University Hospital, Cumana, Venezuela (HUAPA were evaluated. Antimicrobial susceptibility was determined by the disk diffusion method and theaac, aadB and aph genes were detected by PCR. Most of the P. aeruginosa isolates (33/137 were identified from the Intensive Care Unit (ICU, mainly from discharges (96/137. The frequency of resistant P. aeruginosaisolates was found to be higher for the aminoglycosides tobramycin and amikacin (30.7 and 29.9%, respectively. Phenotype VI, resistant to these antibiotics, was the most frequent (14/49, followed by phenotype I, resistant to all the aminoglycosides tested (12/49. The aac(6´-Ib,aphA1 and aadB genes were the most frequently detected, and the simultaneous presence of several resistance genes in the same isolate was demonstrated. Aminoglycoside resistance in isolates ofP. aeruginosa at the HUAPA is partly due to the presence of the aac(6´-Ib, aphA1 andaadB genes, but the high rates of antimicrobial resistance suggest the existence of several mechanisms acting together. This is the first report of aminoglycoside resistance genes in Venezuela and one of the few in Latin America.

  13. At the Nexus of Antibiotics and Metals: The Impact of Cu and Zn on Antibiotic Activity and Resistance.

    Science.gov (United States)

    Poole, Keith

    2017-10-01

    Environmental influences on antibiotic activity and resistance can wreak havoc with in vivo antibiotic efficacy and, ultimately, antimicrobial chemotherapy. In nature, bacteria encounter a variety of metal ions, particularly copper (Cu) and zinc (Zn), as contaminants in soil and water, as feed additives in agriculture, as clinically-used antimicrobials, and as components of human antibacterial responses. Importantly, there is a growing body of evidence for Cu/Zn driving antibiotic resistance development in metal-exposed bacteria, owing to metal selection of genetic elements harbouring both metal and antibiotic resistance genes, and metal recruitment of antibiotic resistance mechanisms. Many classes of antibiotics also form complexes with metal cations, including Cu and Zn, and this can hinder (or enhance) antibiotic activity. This review highlights the ways in which Cu/Zn influence antibiotic resistance development and antibiotic activity, and in so doing impact in vivo antibiotic efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Urine Antibiotic Activity in Patients Presenting to Hospitals in Laos: Implications for Worsening Antibiotic Resistance

    OpenAIRE

    Khennavong, Manisone; Davone, Viengmon; Vongsouvath, Manivanh; Phetsouvanh, Rattanaphone; Silisouk, Joy; Rattana, Olay; Mayxay, Mayfong; Castonguay-Vanier, Josée; Moore, Catrin E.; Strobel, Michel; Newton, Paul N.

    2011-01-01

    Widespread use of antibiotics may be important in the spread of antimicrobial resistance. We estimated the proportion of Lao in- and outpatients who had taken antibiotics before medical consultation by detecting antibiotic activity in their urine added to lawns of Bacillus stearothermophilus, Escherichia coli, and Streptococcus pyogenes. In the retrospective (N = 2,058) and prospective studies (N = 1,153), 49.7% (95% confidence interval [CI] = 47.4–52.0) and 36.2% (95% CI = 33.4–38.9), respec...

  15. Antifungal amphiphilic aminoglycoside K20: bioactivities and mechanism of action

    Directory of Open Access Journals (Sweden)

    Sanjib K. Shrestha

    2014-12-01

    Full Text Available K20 is a novel amphiphilic antifungal aminoglycoside that is synthetically derived from the antibiotic kanamycin A. Reported here are investigations of K20’s antimicrobial activities, cytotoxicity, and fungicidal mechanism of action. In vitro growth inhibitory activities against a variety of human and plant pathogenic yeasts, filamentous fungi, and bacteria were determined using microbroth dilution assays and time-kill curve analyses, and hemolytic and animal cell cytotoxic activities were determined. Effects on Cryptococcus neoformans H-99 infectivity were determined with a preventive murine lung infection model. The antifungal mechanism of action was studied using intact fungal cells, yeast lipid mutants, and small unilamellar lipid vesicles. K20 exhibited broad-spectrum in vitro antifungal activities but not antibacterial activities. Pulmonary, single dose-administration of K20 reduced C. neoformans lung infection rates 4-fold compared to controls. Hemolysis and half-maximal cytotoxicities of mammalian cells occurred at concentrations that were 10 to 32-fold higher than fungicidal MICs. With fluorescein isothiocyanate, 20 to 25 mg/L K20 caused staining of >95% of C. neoformans and Fusarium graminearum cells and at 31.3 mg/L caused rapid leakage (30 to 80% in 15 min of calcein from preloaded small unilamellar lipid vesicles. K20 appears to be a broad-spectrum fungicide, capable of reducing the infectivity of C. neoformans, and exhibits low hemolytic activity and mammalian cell toxicity. It perturbs the plasma membrane by mechanisms that are lipid modulated. K20 is a novel amphiphilic aminoglycoside amenable to scalable production and a potential lead antifungal for therapeutic and crop protection applications.

  16. Entry of aminoglycosides into renal tubular epithelial cells via endocytosis-dependent and endocytosis-independent pathways.

    Science.gov (United States)

    Nagai, Junya; Takano, Mikihisa

    2014-08-15

    Aminoglycoside antibiotics such as gentamicin and amikacin are well recognized as a clinically important antibiotic class because of their reliable efficacy and low cost. However, the clinical use of aminoglycosides is limited by their nephrotoxicity and ototoxicity. Nephrotoxicity is induced mainly due to high accumulation of the antibiotics in renal proximal tubular cells. Therefore, a lot of studies on characterization of the renal transport system for aminoglycosides so far reported involved various in-vivo and in-vitro techniques. Early studies revealed that aminoglycosides are taken up through adsorptive endocytosis in renal epithelial cells. Subsequently, it was found that megalin, a multiligand endocytic receptor abundantly expressed on the apical side of renal proximal tubular cells, can bind aminoglycosides and that megalin-mediated endocytosis plays a crucial role in renal accumulation of aminoglycosides. Therefore, megalin has been suggested to be a promising molecular target for the prevention of aminoglycoside-induced nephrotoxicity. On the other hand, recently, some reports have indicated that aminoglycosides are transported via a pathway that does not require endocytosis, such as non-selective cation channel-mediated entry, in cultured renal tubular cells as well as cochlear outer hair cells. In this commentary article, we review the cellular transport of aminoglycosides in renal epithelial cells, focusing on endocytosis-dependent and -independent pathways. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Activation of the cryptic aac(6')-Iy aminoglycoside resistance gene of Salmonella by a chromosomal deletion generating a transcriptional fusion.

    Science.gov (United States)

    Magnet, S; Courvalin, P; Lambert, T

    1999-11-01

    Salmonella enterica subsp. enterica serotype Enteritidis BM4361 and BM4362 were isolated from the same patient. BM4361 was susceptible to aminoglycosides, whereas BM4362 was resistant to tobramycin owing to synthesis of a 6'-N-acetyltransferase type I [AAC(6')-I]. Comparative analysis of nucleotide sequences, pulsed-field gel electrophoresis patterns, and Southern hybridizations indicated that the chromosomal aac(6')-Iy genes for the enzyme in both strains were identical and that BM4362 derived from BM4361 following a ca. 60-kb deletion that occurred 1.5 kb upstream from the resistance gene. Northern hybridizations showed that aac(6')-Iy was silent in BM4361 and highly expressed in BM4362 due to a transcriptional fusion. Primer extension mapping identified the transcriptional start site for aac(6')-Iy in BM4362: 5 bp downstream from the promoter of the nmpC gene. Study of the distribution of aac(6')-Iy by PCR and Southern hybridization with a specific probe indicated that the gene, although not found in S. enterica subsp. arizonae, was specific for Salmonella. In this bacterial genus, aac(6')-Iy was located downstream from a cluster of seven open reading frames analogous to an Escherichia coli locus that encodes enzymes putatively involved in carbohydrate transport or metabolism. This genomic environment suggests a role in the catabolism of a specific sugar for AAC(6')-Iy in Salmonella.

  18. Chaperonin GroEL/GroES Over-Expression Promotes Aminoglycoside Resistance and Reduces Drug Susceptibilities in Escherichia coli Following Exposure to Sublethal Aminoglycoside Doses

    DEFF Research Database (Denmark)

    Goltermann, Lise; Sarusie, Menachem V; Bentin, Thomas

    2016-01-01

    Antibiotic resistance is an increasing challenge to modern healthcare. Aminoglycoside antibiotics cause translation corruption and protein misfolding and aggregation in Escherichia coli. We previously showed that chaperonin GroEL/GroES depletion and over-expression sensitize and promote short...

  19. Study of the Interference between Plectranthus Species Essential Oils from Brazil and Aminoglycosides.

    Science.gov (United States)

    Galvão Rodrigues, Fabíola Fernandes; Costa, José Galberto Martins; Rodrigues, Fábio Fernandes Galvao; Campos, Adriana Rolim

    2013-01-01

    Plectranthus is one of the most representative genera of Lamiaceae family. In this study, the essential oils from Plectranthus amboinicus, Plectranthus ornatus, and Plectranthus barbatus were investigated for their chemical composition and antimicrobial and modulatory activities. The major components found were carvacrol (54.4%-P. amboinicus) and eugenol (22.9%-P. ornatus e 25.1%-P. barbatus). In vitro antimicrobial activity was conducted against Escherichia coli, Proteus vulgaris, Bacillus cereus, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus aureus (multiresistant) using microdilution method. The results of bioassay showed that all strains were sensitive to the oils, except P. aeruginosa that was resistant to P. amboinicus and P. ornatus. A synergistic effect of all essential oils combined with the aminoglycosides was demonstrated. These results show that P. amboinicus, P. ornatus, and P. barbatus inhibit the growth of pathogenic microorganism, and besides this they present antibiotic modifying activity, providing a new perspective against the problem of bacterial resistance to antibiotics.

  20. Silver enhances antibiotic activity against gram-negative bacteria.

    Science.gov (United States)

    Morones-Ramirez, J Ruben; Winkler, Jonathan A; Spina, Catherine S; Collins, James J

    2013-06-19

    A declining pipeline of clinically useful antibiotics has made it imperative to develop more effective antimicrobial therapies, particularly against difficult-to-treat Gram-negative pathogens. Silver has been used as an antimicrobial since antiquity, yet its mechanism of action remains unclear. We show that silver disrupts multiple bacterial cellular processes, including disulfide bond formation, metabolism, and iron homeostasis. These changes lead to increased production of reactive oxygen species and increased membrane permeability of Gram-negative bacteria that can potentiate the activity of a broad range of antibiotics against Gram-negative bacteria in different metabolic states, as well as restore antibiotic susceptibility to a resistant bacterial strain. We show both in vitro and in a mouse model of urinary tract infection that the ability of silver to induce oxidative stress can be harnessed to potentiate antibiotic activity. Additionally, we demonstrate in vitro and in two different mouse models of peritonitis that silver sensitizes Gram-negative bacteria to the Gram-positive-specific antibiotic vancomycin, thereby expanding the antibacterial spectrum of this drug. Finally, we used silver and antibiotic combinations in vitro to eradicate bacterial persister cells, and show both in vitro and in a mouse biofilm infection model that silver can enhance antibacterial action against bacteria that produce biofilms. This work shows that silver can be used to enhance the action of existing antibiotics against Gram-negative bacteria, thus strengthening the antibiotic arsenal for fighting bacterial infections.

  1. Aminoglycoside interactions and impacts on the eukaryotic ribosome

    Science.gov (United States)

    Prokhorova, Irina; Altman, Roger B.; Djumagulov, Muminjon; Shrestha, Jaya P.; Urzhumtsev, Alexandre; Ferguson, Angelica; Chang, Cheng-Wei Tom; Yusupov, Marat; Blanchard, Scott C.; Yusupova, Gulnara

    2017-01-01

    Aminoglycosides are chemically diverse, broad-spectrum antibiotics that target functional centers within the bacterial ribosome to impact all four principle stages (initiation, elongation, termination, and recycling) of the translation mechanism. The propensity of aminoglycosides to induce miscoding errors that suppress the termination of protein synthesis supports their potential as therapeutic interventions in human diseases associated with premature termination codons (PTCs). However, the sites of interaction of aminoglycosides with the eukaryotic ribosome and their modes of action in eukaryotic translation remain largely unexplored. Here, we use the combination of X-ray crystallography and single-molecule FRET analysis to reveal the interactions of distinct classes of aminoglycosides with the 80S eukaryotic ribosome. Crystal structures of the 80S ribosome in complex with paromomycin, geneticin (G418), gentamicin, and TC007, solved at 3.3- to 3.7-Å resolution, reveal multiple aminoglycoside-binding sites within the large and small subunits, wherein the 6′-hydroxyl substituent in ring I serves as a key determinant of binding to the canonical eukaryotic ribosomal decoding center. Multivalent binding interactions with the human ribosome are also evidenced through their capacity to affect large-scale conformational dynamics within the pretranslocation complex that contribute to multiple aspects of the translation mechanism. The distinct impacts of the aminoglycosides examined suggest that their chemical composition and distinct modes of interaction with the ribosome influence PTC read-through efficiency. These findings provide structural and functional insights into aminoglycoside-induced impacts on the eukaryotic ribosome and implicate pleiotropic mechanisms of action beyond decoding. PMID:29208708

  2. Bacteriostatic activity of various antibiotics after gamma-ray irradiation

    International Nuclear Information System (INIS)

    Fleurette, J.; Madier, S.; Transy, M.J.

    1975-01-01

    The purpose of the work described was to discover whether the antibiotics used in medicine can be sterilized by gamma rays; in this preliminary study, only the antimicrobic activity - the principal criterion for this type of medicament - was evaluated. Thirty-three products belonging to the various families of antibacterial and antifungic antibiotics were studied. The substances were irradiated in the dry state and in an aqueous solution, using a caesium-137 irradiator. The antibacterial and antifungic activity before and after irradiation was investigated by the method of diffusion in gelose. When irradiated in the dry state, 14 antibiotics preserve normal activity up to a dose of 10 Mrad; at doses between 5 and 10 Mrad, 15 other antibiotics are subject to a variable, but moderate, loss activity; and four register a slight loss of activity at a dose of 2.5 Mrad. In an aqueous solution all but two of the antibiotics suffer total loss of activity at a dose of 2.5 Mrad. As most commercial antibiotics are supplied in the dry state, gamma irradiation may be a useful sterilization process. However, preparations such as eye lotions, suspensions, ointments, etc. should be excepted

  3. Discovery of Antibiotics-derived Polymers for Gene Delivery using Combinatorial Synthesis and Cheminformatics Modeling

    Science.gov (United States)

    Potta, Thrimoorthy; Zhen, Zhuo; Grandhi, Taraka Sai Pavan; Christensen, Matthew D.; Ramos, James; Breneman, Curt M.; Rege, Kaushal

    2014-01-01

    We describe the combinatorial synthesis and cheminformatics modeling of aminoglycoside antibiotics-derived polymers for transgene delivery and expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides with diglycidyl ether cross-linkers. Parallel screening resulted in identification of several lead polymers that resulted in high transgene expression levels in cells. The role of polymer physicochemical properties in determining efficacy of transgene expression was investigated using Quantitative Structure-Activity Relationship (QSAR) cheminformatics models based on Support Vector Regression (SVR) and ‘building block’ polymer structures. The QSAR model exhibited high predictive ability, and investigation of descriptors in the model, using molecular visualization and correlation plots, indicated that physicochemical attributes related to both, aminoglycosides and diglycidyl ethers facilitated transgene expression. This work synergistically combines combinatorial synthesis and parallel screening with cheminformatics-based QSAR models for discovery and physicochemical elucidation of effective antibiotics-derived polymers for transgene delivery in medicine and biotechnology. PMID:24331709

  4. Discovery of antibiotics-derived polymers for gene delivery using combinatorial synthesis and cheminformatics modeling.

    Science.gov (United States)

    Potta, Thrimoorthy; Zhen, Zhuo; Grandhi, Taraka Sai Pavan; Christensen, Matthew D; Ramos, James; Breneman, Curt M; Rege, Kaushal

    2014-02-01

    We describe the combinatorial synthesis and cheminformatics modeling of aminoglycoside antibiotics-derived polymers for transgene delivery and expression. Fifty-six polymers were synthesized by polymerizing aminoglycosides with diglycidyl ether cross-linkers. Parallel screening resulted in identification of several lead polymers that resulted in high transgene expression levels in cells. The role of polymer physicochemical properties in determining efficacy of transgene expression was investigated using Quantitative Structure-Activity Relationship (QSAR) cheminformatics models based on Support Vector Regression (SVR) and 'building block' polymer structures. The QSAR model exhibited high predictive ability, and investigation of descriptors in the model, using molecular visualization and correlation plots, indicated that physicochemical attributes related to both, aminoglycosides and diglycidyl ethers facilitated transgene expression. This work synergistically combines combinatorial synthesis and parallel screening with cheminformatics-based QSAR models for discovery and physicochemical elucidation of effective antibiotics-derived polymers for transgene delivery in medicine and biotechnology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  5. Cryptic antifungal compounds active by synergism with polyene antibiotics.

    Science.gov (United States)

    Kinoshita, Hiroshi; Yoshioka, Mariko; Ihara, Fumio; Nihira, Takuya

    2016-04-01

    The majority of antifungal compounds reported so far target the cell wall or cell membrane of fungi, suggesting that other types of antibiotics cannot exert their activity because they cannot penetrate into the cells. Therefore, if the permeability of the cell membrane could be enhanced, many antibiotics might be found to have antifungal activity. We here used the polyene antibiotic nystatin, which binds to ergosterol and forms pores at the cell membrane, to enhance the cellular permeability. In the presence of nystatin, many culture extracts from entomopathogenic fungi displayed antifungal activity. Among all the active extracts, two active components were purified and identified as helvolic acid and terramide A. Because the minimum inhibitory concentration of either compound was reduced four-fold in the presence of nystatin, it can be concluded that this screening method is useful for detecting novel antifungal activity. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  6. Structure of the phosphotransferase domain of the bifunctional aminoglycoside-resistance enzyme AAC(6')-Ie-APH(2'')-Ia.

    Science.gov (United States)

    Smith, Clyde A; Toth, Marta; Bhattacharya, Monolekha; Frase, Hilary; Vakulenko, Sergei B

    2014-06-01

    The bifunctional acetyltransferase(6')-Ie-phosphotransferase(2'')-Ia [AAC(6')-Ie-APH(2'')-Ia] is the most important aminoglycoside-resistance enzyme in Gram-positive bacteria, conferring resistance to almost all known aminoglycoside antibiotics in clinical use. Owing to its importance, this enzyme has been the focus of intensive research since its isolation in the mid-1980s but, despite much effort, structural details of AAC(6')-Ie-APH(2'')-Ia have remained elusive. The structure of the Mg2GDP complex of the APH(2'')-Ia domain of the bifunctional enzyme has now been determined at 2.3 Å resolution. The structure of APH(2'')-Ia is reminiscent of the structures of other aminoglycoside phosphotransferases, having a two-domain architecture with the nucleotide-binding site located at the junction of the two domains. Unlike the previously characterized APH(2'')-IIa and APH(2'')-IVa enzymes, which are capable of utilizing both ATP and GTP as the phosphate donors, APH(2'')-Ia uses GTP exclusively in the phosphorylation of the aminoglycoside antibiotics, and in this regard closely resembles the GTP-dependent APH(2'')-IIIa enzyme. In APH(2'')-Ia this GTP selectivity is governed by the presence of a `gatekeeper' residue, Tyr100, the side chain of which projects into the active site and effectively blocks access to the adenine-binding template. Mutation of this tyrosine residue to a less bulky phenylalanine provides better access for ATP to the NTP-binding template and converts APH(2'')-Ia into a dual-specificity enzyme.

  7. Potentiation of Aminoglycoside Activity in Pseudomonas aeruginosa by Targeting the AmgRS Envelope Stress-Responsive Two-Component System.

    Science.gov (United States)

    Poole, Keith; Gilmour, Christie; Farha, Maya A; Mullen, Erin; Lau, Calvin Ho-Fung; Brown, Eric D

    2016-06-01

    A screen for agents that potentiated the activity of paromomycin (PAR), a 4,5-linked aminoglycoside (AG), against wild-type Pseudomonas aeruginosa identified the RNA polymerase inhibitor rifampin (RIF). RIF potentiated additional 4,5-linked AGs, such as neomycin and ribostamycin, but not the clinically important 4,6-linked AGs amikacin and gentamicin. Potentiation was absent in a mutant lacking the AmgRS envelope stress response two-component system (TCS), which protects the organism from AG-generated membrane-damaging aberrant polypeptides and, thus, promotes AG resistance, an indication that RIF was acting via this TCS in potentiating 4,5-linked AG activity. Potentiation was also absent in a RIF-resistant RNA polymerase mutant, consistent with its potentiation of AG activity being dependent on RNA polymerase perturbation. PAR-inducible expression of the AmgRS-dependent genes htpX and yccA was reduced by RIF, suggesting that AG activation of this TCS was compromised by this agent. Still, RIF did not compromise the membrane-protective activity of AmgRS, an indication that it impacted some other function of this TCS. RIF potentiated the activities of 4,5-linked AGs against several AG-resistant clinical isolates, in two cases also potentiating the activity of the 4,6-linked AGs. These cases were, in one instance, explained by an observed AmgRS-dependent expression of the MexXY multidrug efflux system, which accommodates a range of AGs, with RIF targeting of AmgRS undermining mexXY expression and its promotion of resistance to 4,5- and 4,6-linked AGs. Given this link between AmgRS, MexXY expression, and pan-AG resistance in P. aeruginosa, RIF might be a useful adjuvant in the AG treatment of P. aeruginosa infections. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  8. Chaperonins fight aminoglycoside-induced protein misfolding and promote short-term tolerance in Escherichia coli

    DEFF Research Database (Denmark)

    Goltermann, Lise; Good, Liam; Bentin, Thomas

    2013-01-01

    For almost half of a century, we have known that aminoglycoside antibiotics corrupt ribosomes, causing translational misreading, yet it remains unclear whether or not misreading triggers protein misfolding, and possible effects of chaperone action on drug susceptibilities are poorly understood...... as measured by reduced minimum inhibitory concentrations, whereas GroEL/GroES overexpression did not increase minimum inhibitory concentrations. Our observations establish misfolding of cytosolic proteins as an effect of aminoglycoside action and reveal that chaperones, chaperonins in particular, help...

  9. Genetic basis of enzymatic resistance of E. coli to aminoglycosides.

    Science.gov (United States)

    Ojdana, Dominika; Sieńko, Anna; Sacha, Paweł; Majewski, Piotr; Wieczorek, Piotr; Wieczorek, Anna; Tryniszewska, Elżbieta

    2017-07-29

    Over the past years, an increase in resistance to aminoglycosides has been observed among Enterobacteriaceae rods. This resistance development reduces therapeutic options for infections caused by multidrug-resistance organisms. Because of the changing epidemiology of extended-spectrum β-lactamases (ESBLs) and resistance to aminoglycosides, we investigated the prevalence of the aac(3)-Ia, aac(6')-Ib, ant(4')-IIa, ant(2")-Ia, and aph(3")-Ib genes encoding aminoglycoside-modifying enzymes (AMEs) in ESBL-producing Escherichia coli as well as ESBL-non-producing isolates. To understand bacterial resistance to aminoglycoside antibiotics, we estimated resistance phenotypes and the presence of genes responsible for this resistance. The study was conducted on 44 E.coli strains originated from patients hospitalized at University Hospital of Bialystok. MIC values were obtained for gentamicin, amikacin, netilmicin, and tobramycin. Isolates were tested for the presence of the aac(3)-Ia, aac(6')-Ib, ant(4')-IIa, ant(2")-Ia, and aph(3")-Ib genes with the use of the PCR technique. Resistance to aminoglycosides was found in 79.5% of the isolates. The highest percentages of resistance were observed for tobramycin (70,5%) and gentamicin (59%), followed by netilmicin (43.2%) and amikacin (11.4%). PCR assays revealed the presence of aac(6')-Ib among 26 (59.2%) strains, aph(3")-Ib among 16 (36.2%), aac(3)-Ia among 7 (15.9%), and ant(2")-Ia among 2 (4.6%) strains. The enzymatic resistance against aminoglycosides in northeastern Poland among clinical isolates of E. coli is predominantly caused by aac(6')-Ib and aph(3")-Ib. Amikacin may be used for therapy of infections caused by ESBL-producing E. coli, because of the low rates of resistance. Copyright © 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.

  10. Anti-tuberculosis activity of -lactam antibiotics: prospects for the ...

    African Journals Online (AJOL)

    This review is prepared to show results on the anti-TB activity of -lactam antibiotics. -Lactams are among the oldest drugs with little or no side effects. Both in vitro studies and clinical data indicate that -lactams have a promising activity for use in the management of MDR-TB. More studies are required to define the interaction ...

  11. Bacterial Enzymes and Antibiotic Resistance- Oral Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Maltz, Lauren [SLAC National Accelerator Lab., Menlo Park, CA (United States)

    2015-08-25

    By using protein crystallography and X-ray diffraction, structures of bacterial enzymes were solved to gain a better understanding of how enzymatic modification acts as an antibacterial resistance mechanism. Aminoglycoside phosphotransferases (APHs) are one of three aminoglycoside modifying enzymes that confer resistance to the aminoglycoside antibiotics via enzymatic modification, rendering many drugs obsolete. Specifically, the APH(2”) family vary in their substrate specificities and also in their preference for the phosphate donor (ADP versus GDP). By solving the structures of members of the APH(2”) family of enzymes, we can see how domain movements are important to their substrate specificity. Our structure of the ternary complex of APH(2”)-IIIa with GDP and kanamycin, when compared to the known structures of APH(2”)-IVa, reveals that there are real physical differences between these two enzymes, a structural finding that explains why the two enzymes differ in their preferences for certain aminoglycosides. Another important group of bacterial resistance enzymes are the Class D β-lactamases. Oxacillinase carbapenemases (OXAs) are part of this enzyme class and have begun to confer resistance to ‘last resort’ drugs, most notably carbapenems. Our structure of OXA-143 shows that the conformational flexibility of a conserved hydrophobic residue in the active site (Val130) serves to control the entry of a transient water molecule responsible for a key step in the enzyme’s mechanism. Our results provide insight into the structural mechanisms of these two different enzymes.

  12. Ligand promiscuity through the eyes of the aminoglycoside N3 acetyltransferase IIa.

    Science.gov (United States)

    Norris, Adrianne L; Serpersu, Engin H

    2013-07-01

    Aminoglycoside-modifying enzymes (AGMEs) are expressed in many pathogenic bacteria and cause resistance to aminoglycoside (AG) antibiotics. Remarkably, the substrate promiscuity of AGMEs is quite variable. The molecular basis for such ligand promiscuity is largely unknown as there is not an obvious link between amino acid sequence or structure and the antibiotic profiles of AGMEs. To address this issue, this article presents the first kinetic and thermodynamic characterization of one of the least promiscuous AGMEs, the AG N3 acetyltransferase-IIa (AAC-IIa) and its comparison to two highly promiscuous AGMEs, the AG N3-acetyltransferase-IIIb (AAC-IIIb) and the AG phosphotransferase(3')-IIIa (APH). Despite having similar antibiotic selectivities, AAC-IIIb and APH catalyze different reactions and share no homology to one another. AAC-IIa and AAC-IIIb catalyze the same reaction and are very similar in both amino acid sequence and structure. However, they demonstrate strong differences in their substrate profiles and kinetic and thermodynamic properties. AAC-IIa and APH are also polar opposites in terms of ligand promiscuity but share no sequence or apparent structural homology. However, they both are highly dynamic and may even contain disordered segments and both adopt well-defined conformations when AGs are bound. Contrary to this AAC-IIIb maintains a well-defined structure even in apo form. Data presented herein suggest that the antibiotic promiscuity of AGMEs may be determined neither by the flexibility of the protein nor the size of the active site cavity alone but strongly modulated or controlled by the effects of the cosubstrate on the dynamic and thermodynamic properties of the enzyme. Copyright Copyright © 2013 The Protein Society.

  13. Appropriateness of aminoglycoside prescriptions in a French university hospital.

    Science.gov (United States)

    Muller, A; Leroy, J; Patry, I; Hénon, T; Hocquet, D; Chirouze, C; Bertrand, X

    2016-09-01

    Aminoglycosides are a major class of antibiotics. Their use is particularly interesting in the treatment of severe infections but their toxicity is well known. They are mostly prescribed combined with other agents and as first-line treatments. We aimed to assess the appropriateness of aminoglycoside prescriptions in a French university hospital on the basis of the latest French recommendations published in 2011. We conducted a prospective study between January 17th and February 4th, 2014 to assess prescription modalities of aminoglycosides on the basis of the following criteria: indication, duration of treatment, dosing schedule, administration modalities, and drug level monitoring. Prescriptions were then compared to the 2011 national guidelines. A total of 68 consecutive prescriptions were analyzed and only 47.8% complied with guidelines. Most physicians complied with recommendations, particularly with the indication for severe infections (95.6%), the administration of a single daily dose (92.6%), and the slow intravenous infusion (30minutes) administration (84%). However, physicians tended to prescribe lower doses than recommended (40.3%), especially to patients presenting with renal insufficiency, and drug level monitoring was not optimal. Although new and accurate national recommendations were recently published, aminoglycoside prescription is still not optimal, in particular for dosing and plasma concentration monitoring. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  14. In vitro susceptibility pattern of acinetobacter species to commonly used cephalosporins, quinolones, and aminoglycosides

    Directory of Open Access Journals (Sweden)

    Prashanth K

    2004-01-01

    Full Text Available PURPOSE: Acinetobacter spp. is an emerging important nosocomial pathogen. Clinical isolates of this genus are often resistant to many antibiotics. The in vitro susceptibility of Acinetobacter isolates obtained from patients were tested for currently used antibiotics. In addition, the study aimed at biotyping of Acinetobacter baumannii. METHODS: A total of 66 isolates were phenotypically characterised through a large panel of 25 carbon assimilation tests and susceptibility through disc diffusion method with 10 antimicrobial agents were tested. MICs were determined only for second line broad-spectrum drugs such as cefotaxime, ceftazidime, amikacin, ciprofloxacin, and ofloxacin using NCCLS guidelines. RESULTS: Multiple drug resistance (MDR was only witnessed in A. baumannii and not in other Acinetobacter species. Aminoglycosides such as amikacin, netilmicin were most active against the MDR isolates tested (60% susceptibility. Ceftazidime was more active than cefotaxime. MDR A. baumannii strains were susceptible only to amikacin, netilmicin and ceftadizime. Ciprofloxacin had poor activity irrespective of isolates belonging to different DNA groups tested (58% resistance overall, 79% among A. baumannii. Strains of Biotypes 6 and 19 of A. baumannii showed broader resistance than those of biotype 10 and others. CONCLUSIONS: Strains of A. baumannii from patients in our hospital, were generally more resistant to quinolones, -lactam antibiotics, first and second generation cephalosporins and partially resistant to third generation cephalosporins and aminoglycosides. The strains belonging to other DNA groups of Acinetobacter were comparatively less resistant than A.baumannii, except ciprofloxacin. This study suggests that, a combination therapy, using a third generation cephalosporin and amikacin, would be best choice for treating Acinetobacter infections.

  15. Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria.

    Directory of Open Access Journals (Sweden)

    Divakara S S M Uppu

    Full Text Available Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin to biofilms of Gram-negative bacteria. These molecules eliminate planktonic bacteria that are liberated after dispersion of biofilms (dispersed cells. The membrane-active mechanism of these molecules forms the key for potentiating the established antibiotics. Further, we demonstrate that the combination of macromolecules and antibiotics significantly reduces bacterial burden in mouse burn and surgical wound infection models caused by Acinetobacter baumannii and Carbapenemase producing Klebsiella pneumoniae (KPC clinical isolate respectively. Colistin, a well-known antibiotic targeting the lipopolysaccharide (LPS of Gram-negative bacteria fails to kill antibiotic tolerant cells and dispersed cells (from biofilms and bacteria develop resistance to it. On the contrary, these macromolecules prevent or delay the development of bacterial resistance to known antibiotics. Our findings emphasize the potential of targeting the bacterial membrane in antibiotic potentiation for disruption of biofilms and suggest a promising strategy towards developing therapies for topical treatment of Gram-negative infections.

  16. Membrane-active macromolecules kill antibiotic-tolerant bacteria and potentiate antibiotics towards Gram-negative bacteria.

    Science.gov (United States)

    Uppu, Divakara S S M; Konai, Mohini M; Sarkar, Paramita; Samaddar, Sandip; Fensterseifer, Isabel C M; Farias-Junior, Celio; Krishnamoorthy, Paramanandam; Shome, Bibek R; Franco, Octávio L; Haldar, Jayanta

    2017-01-01

    Chronic bacterial biofilms place a massive burden on healthcare due to the presence of antibiotic-tolerant dormant bacteria. Some of the conventional antibiotics such as erythromycin, vancomycin, linezolid, rifampicin etc. are inherently ineffective against Gram-negative bacteria, particularly in their biofilms. Here, we report membrane-active macromolecules that kill slow dividing stationary-phase and antibiotic tolerant cells of Gram-negative bacteria. More importantly, these molecules potentiate antibiotics (erythromycin and rifampicin) to biofilms of Gram-negative bacteria. These molecules eliminate planktonic bacteria that are liberated after dispersion of biofilms (dispersed cells). The membrane-active mechanism of these molecules forms the key for potentiating the established antibiotics. Further, we demonstrate that the combination of macromolecules and antibiotics significantly reduces bacterial burden in mouse burn and surgical wound infection models caused by Acinetobacter baumannii and Carbapenemase producing Klebsiella pneumoniae (KPC) clinical isolate respectively. Colistin, a well-known antibiotic targeting the lipopolysaccharide (LPS) of Gram-negative bacteria fails to kill antibiotic tolerant cells and dispersed cells (from biofilms) and bacteria develop resistance to it. On the contrary, these macromolecules prevent or delay the development of bacterial resistance to known antibiotics. Our findings emphasize the potential of targeting the bacterial membrane in antibiotic potentiation for disruption of biofilms and suggest a promising strategy towards developing therapies for topical treatment of Gram-negative infections.

  17. Antimicrobial spectra and activities of antibiotic substances from ...

    African Journals Online (AJOL)

    Antimicrobial substances were produced from several Streptomyces species isolated from the soil. The antimicrobial spectra of the antibiotic substances assayed by agar-diffusion technique demonstrated broad-spectrum antimicrobial activity against Staphylococcus aureus, coagulase-negative Staphylococcus aureus, ...

  18. Characterization and Antibacterial Activity of a Glycoside Antibiotic ...

    African Journals Online (AJOL)

    In the present study, characterization and antibacterial activity of a glycoside antibiotic from fermentation broth of bioactive Streptomyces variabilis PO-178 recovered previously from Western Ghat soil of Agumbe, Karnataka, India was investigated. Mass cultivation of the strain PO-178 was carried out in Starch casein nitrate ...

  19. High Level Aminoglycoside Resistance and Distribution of Aminoglycoside Resistant Genes among Clinical Isolates of Enterococcus Species in Chennai, India

    Directory of Open Access Journals (Sweden)

    Elango Padmasini

    2014-01-01

    Full Text Available Enterococci are nosocomial pathogen with multiple-drug resistance by intrinsic and extrinsic mechanisms. Aminoglycosides along with cell wall inhibitors are given clinically for treating enterococcal infections. 178 enterococcal isolates were analyzed in this study. E. faecalis is identified to be the predominant Enterococcus species, along with E. faecium, E. avium, E. hirae, E. durans, E. dispar and E. gallinarum. High level aminoglycoside resistance (HLAR by MIC for gentamicin (GM, streptomycin (SM and both (GM + SM antibiotics was found to be 42.7%, 29.8%, and 21.9%, respectively. Detection of aminoglycoside modifying enzyme encoding genes (AME in enterococci was identified by multiplex PCR for aac(6′-Ie-aph(2′′-Ia; aph(2′′-Ib; aph(2′′-Ic; aph(2′′-Id and aph(3′-IIIa genes. 38.2% isolates carried aac(6′-Ie-aph(2′′-Ia gene and 40.4% isolates carried aph(3′-IIIa gene. aph(2′′-Ib; aph(2′′-Ic; aph(2′′-Id were not detected among our study isolates. aac(6′-Ie-aph(2′′-Ia and aph(3′-IIIa genes were also observed in HLAR E. durans, E. avium, E. hirae, and E. gallinarum isolates. This indicates that high level aminoglycoside resistance genes are widely disseminated among isolates of enterococci from Chennai.

  20. Carbon Sources Tune Antibiotic Susceptibility in Pseudomonas aeruginosa via Tricarboxylic Acid Cycle Control.

    Science.gov (United States)

    Meylan, Sylvain; Porter, Caroline B M; Yang, Jason H; Belenky, Peter; Gutierrez, Arnaud; Lobritz, Michael A; Park, Jihye; Kim, Sun H; Moskowitz, Samuel M; Collins, James J

    2017-02-16

    Metabolically dormant bacteria present a critical challenge to effective antimicrobial therapy because these bacteria are genetically susceptible to antibiotic treatment but phenotypically tolerant. Such tolerance has been attributed to impaired drug uptake, which can be reversed by metabolic stimulation. Here, we evaluate the effects of central carbon metabolite stimulations on aminoglycoside sensitivity in the pathogen Pseudomonas aeruginosa. We identify fumarate as a tobramycin potentiator that activates cellular respiration and generates a proton motive force by stimulating the tricarboxylic acid (TCA) cycle. In contrast, we find that glyoxylate induces phenotypic tolerance by inhibiting cellular respiration with acetyl-coenzyme A diversion through the glyoxylate shunt, despite drug import. Collectively, this work demonstrates that TCA cycle activity is important for both aminoglycoside uptake and downstream lethality and identifies a potential strategy for potentiating aminoglycoside treatment of P. aeruginosa infections. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Looking for new preparations for antibacterial therapy. IV. New antimicrobial agents from the aminoglycoside, macrolide and tetracycline groups in clinical trials.

    Science.gov (United States)

    Karpiuk, Izabela; Tyski, Stefan

    2015-01-01

    This paper is the fourth in a series on the search for new antibacterial therapies, and covers new compounds belonging to the aminoglycoside, macrolide and tetracycline groups of antibiotics. The article describes eight new substances at the clinical trial stage of development. One of them is an aminoglycoside (plazomicin), four are macrolides, collectively known as ketolides (cethromycin, solithromycin, EDP-420 and EDP-788), and the remaining three are members of the tetracycline group (omadacycline, eravacycline, sarecycline). Despite the long-term and very expensive process of collecting documentation proving the efficacy of antimicrobial drugs, there is a possibility, that particular compounds find use as active ingredients of medicinal products allowing for the triumph over the clinically relevant, dangerous bacteria.

  2. Activating and Attenuating the Amicoumacin Antibiotics.

    Science.gov (United States)

    Park, Hyun Bong; Perez, Corey E; Perry, Elena Kim; Crawford, Jason M

    2016-06-24

    The amicoumacins belong to a class of dihydroisocoumarin natural products and display antibacterial, antifungal, anticancer, and anti-inflammatory activities. Amicoumacins are the pro-drug activation products of a bacterial nonribosomal peptide-polyketide hybrid biosynthetic pathway and have been isolated from Gram-positive Bacillus and Nocardia species. Here, we report the stimulation of a "cryptic" amicoumacin pathway in the entomopathogenic Gram-negative bacterium Xenorhabdus bovienii, a strain not previously known to produce amicoumacins. X. bovienii participates in a multi-lateral symbiosis where it is pathogenic to insects and mutualistic to its Steinernema nematode host. Waxmoth larvae are common prey of the X. bovienii-Steinernema pair. Employing a medium designed to mimic the amino acid content of the waxmoth circulatory fluid led to the detection and characterization of amicoumacins in X. bovienii. The chemical structures of the amicoumacins were supported by 2D-NMR, HR-ESI-QTOF-MS, tandem MS, and polarimeter spectral data. A comparative gene cluster analysis of the identified X. bovienii amicoumacin pathway to that of the Bacillus subtilis amicoumacin pathway and the structurally-related Xenorhabdus nematophila xenocoumacin pathway is presented. The X. bovienii pathway encodes an acetyltransferase not found in the other reported pathways, which leads to a series of N-acetyl-amicoumacins that lack antibacterial activity. N-acetylation of amicoumacin was validated through in vitro protein biochemical studies, and the impact of N-acylation on amicoumacin's mode of action was examined through ribosomal structural analyses.

  3. Antibacterial and antibiotic potentiating activities of tropical marine sponge extracts.

    Science.gov (United States)

    Beesoo, Rima; Bhagooli, Ranjeet; Neergheen-Bhujun, Vidushi S; Li, Wen-Wu; Kagansky, Alexander; Bahorun, Theeshan

    2017-06-01

    Increasing prevalence of antibiotic resistance has led research to focus on discovering new antimicrobial agents derived from the marine biome. Although ample studies have investigated sponges for their bioactive metabolites with promising prospects in drug discovery, the potentiating effects of sponge extracts on antibiotics still remains to be expounded. The present study aimed to investigate the antibacterial capacity of seven tropical sponges collected from Mauritian waters and their modulatory effect in association with three conventional antibiotics namely chloramphenicol, ampicillin and tetracycline. Disc diffusion assay was used to determine the inhibition zone diameter (IZD) of the sponge total crude extracts (CE), hexane (HF), ethyl acetate (EAF) and aqueous (AF) fractions against nine standard bacterial isolates whereas broth microdilution method was used to determine their minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs) and antibiotic potentiating activity of the most active sponge extract. MIC values of the sponge extracts ranged from 0.039 to 1.25mg/mL. Extracts from Neopetrosia exigua rich in beta-sitosterol and cholesterol displayed the widest activity spectrum against the 9 tested bacterial isolates whilst the best antibacterial profile was observed by its EAF particularly against Staphylococcus aureus and Bacillus cereus with MIC and MBC values of 0.039mg/mL and 0.078mg/mL, respectively. The greatest antibiotic potentiating effect was obtained with the EAF of N. exigua (MIC/2) and ampicillin combination against S. aureus. These findings suggest that the antibacterial properties of the tested marine sponge extracts may provide an alternative and complementary strategy to manage bacterial infections. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Activating and Attenuating the Amicoumacin Antibiotics

    Directory of Open Access Journals (Sweden)

    Hyun Bong Park

    2016-06-01

    Full Text Available The amicoumacins belong to a class of dihydroisocoumarin natural products and display antibacterial, antifungal, anticancer, and anti-inflammatory activities. Amicoumacins are the pro-drug activation products of a bacterial nonribosomal peptide-polyketide hybrid biosynthetic pathway and have been isolated from Gram-positive Bacillus and Nocardia species. Here, we report the stimulation of a “cryptic” amicoumacin pathway in the entomopathogenic Gram-negative bacterium Xenorhabdus bovienii, a strain not previously known to produce amicoumacins. X. bovienii participates in a multi-lateral symbiosis where it is pathogenic to insects and mutualistic to its Steinernema nematode host. Waxmoth larvae are common prey of the X. bovienii-Steinernema pair. Employing a medium designed to mimic the amino acid content of the waxmoth circulatory fluid led to the detection and characterization of amicoumacins in X. bovienii. The chemical structures of the amicoumacins were supported by 2D-NMR, HR-ESI-QTOF-MS, tandem MS, and polarimeter spectral data. A comparative gene cluster analysis of the identified X. bovienii amicoumacin pathway to that of the Bacillus subtilis amicoumacin pathway and the structurally-related Xenorhabdus nematophila xenocoumacin pathway is presented. The X. bovienii pathway encodes an acetyltransferase not found in the other reported pathways, which leads to a series of N-acetyl-amicoumacins that lack antibacterial activity. N-acetylation of amicoumacin was validated through in vitro protein biochemical studies, and the impact of N-acylation on amicoumacin’s mode of action was examined through ribosomal structural analyses.

  5. Functional hair cell mechanotransducer channels are required for aminoglycoside ototoxicity.

    Directory of Open Access Journals (Sweden)

    Abdelrahman Alharazneh

    Full Text Available Aminoglycosides (AG are commonly prescribed antibiotics with potent bactericidal activities. One main side effect is permanent sensorineural hearing loss, induced by selective inner ear sensory hair cell death. Much work has focused on AG's initiating cell death processes, however, fewer studies exist defining mechanisms of AG uptake by hair cells. The current study investigated two proposed mechanisms of AG transport in mammalian hair cells: mechanotransducer (MET channels and endocytosis. To study these two mechanisms, rat cochlear explants were cultured as whole organs in gentamicin-containing media. Two-photon imaging of Texas Red conjugated gentamicin (GTTR uptake into live hair cells was rapid and selective. Hypocalcemia, which increases the open probability of MET channels, increased AG entry into hair cells. Three blockers of MET channels (curare, quinine, and amiloride significantly reduced GTTR uptake, whereas the endocytosis inhibitor concanavalin A did not. Dynosore quenched the fluorescence of GTTR and could not be tested. Pharmacologic blockade of MET channels with curare or quinine, but not concanavalin A or dynosore, prevented hair cell loss when challenged with gentamicin for up to 96 hours. Taken together, data indicate that the patency of MET channels mediated AG entry into hair cells and its toxicity. Results suggest that limiting permeation of AGs through MET channel or preventing their entry into endolymph are potential therapeutic targets for preventing hair cell death and hearing loss.

  6. Vancomycin-resistant enterococci: validation of susceptibility testing and in vitro activity of novel antibiotics

    DEFF Research Database (Denmark)

    Rathe, Mathias; Lise, Kristensen,; Ellermann-Eriksen, Svend

    Vancomycin-resistant enterococci: validation of susceptibility testing and in vitro activity of novel antibiotics......Vancomycin-resistant enterococci: validation of susceptibility testing and in vitro activity of novel antibiotics...

  7. Antibiotics.

    Science.gov (United States)

    Hariprasad, Seenu M; Mieler, William F

    2016-01-01

    The Endophthalmitis Vitrectomy Study (EVS) provided ophthalmologists with evidence-based management strategies to deal with endophthalmitis for the first time. However, since the completion of the EVS, numerous unresolved issues remain. The use of oral antibiotics has important implications for the ophthalmologist, particularly in the prophylaxis and/or management of postoperative, posttraumatic, or bleb-associated bacterial endophthalmitis. One can reasonably conclude that significant intraocular penetration of an antibiotic after oral administration may be a property unique to the newer-generation fluoroquinolones. Prophylactic use of mupirocin nasal ointment resulted in significant reduction of conjunctival flora with or without preoperative topical 5% povidone-iodine preparation. Ocular fungal infections have traditionally been very difficult to treat due to limited therapeutic options both systemically and intravitreally. Because of its broad spectrum of coverage, low MIC90 levels for the organisms of concern, good tolerability, and excellent bioavailability, voriconazole through various routes of administration may be useful to the ophthalmologist in the primary treatment of or as an adjunct to the current management of ocular fungal infections. © 2016 S. Karger AG, Basel.

  8. Protective effect of rasagiline in aminoglycoside ototoxicity.

    Science.gov (United States)

    Polony, G; Humli, V; Andó, R; Aller, M; Horváth, T; Harnos, A; Tamás, L; Vizi, E S; Zelles, T

    2014-04-18

    Sensorineural hearing losses (SNHLs; e.g., ototoxicant- and noise-induced hearing loss or presbycusis) are among the most frequent sensory deficits, but they lack effective drug therapies. The majority of recent therapeutic approaches focused on the trials of antioxidants and reactive oxygen species (ROS) scavengers in SNHLs. The rationale for these studies was the prominent role of disturbed redox homeostasis and the consequent ROS elevation. Although the antioxidant therapies in several animal studies seemed to be promising, clinical trials have failed to fulfill expectations. We investigated the potential of rasagiline, an FDA-approved monomanine oxidase type B inhibitor (MAO-B) inhibitor type anti-parkinsonian drug, as an otoprotectant. We showed a dose-dependent alleviation of the kanamycin-induced threshold shifts measured by auditory brainstem response (ABR) in an ototoxicant aminoglycoside antibiotic-based hearing loss model in mice. This effect proved to be statistically significant at a 6-mg/kg (s.c.) dose. The most prominent effect appeared at 16kHz, which is the hearing sensitivity optimum for mice. The neuroprotective, antiapoptotic and antioxidant effects of rasagiline in animal models, all targeting a specific mechanism of aminoglycoside injury, may explain this otoprotection. The dopaminergic neurotransmission enhancer effect of rasagiline might also contribute to the protection. Dopamine (DA), released from lateral olivocochlear (LOC) fibers, was shown to exert a protective action against excitotoxicity, a pathological factor in the aminoglycoside-induced SNHL. We have shown that rasagiline enhanced the electric stimulation-evoked release of DA from an acute mouse cochlea preparation in a dose-dependent manner. Using inhibitors of voltage-gated Na(+)-, Ca(2+) channels and DA transporters, we revealed that rasagiline potentiated the action potential-evoked release of DA by inhibiting the reuptake. The complex, multifactorial pathomechanism of SNHLs

  9. Antibiofilm Activity of Manuka Honey in Combination with Antibiotics

    OpenAIRE

    Campeau, Michelle E. M.; Patel, Robin

    2014-01-01

    We assessed the in vitro activity of Manuka honey against biofilm bacteria in combination with antibiotics and visualized the effect of Manuka honey on bacterial biofilms using scanning electron microscopy. The fractional biofilm eradication concentration (∑FBEC ) index for vancomycin plus Manuka honey against S. aureus IDRL-4284 biofilms was 0.34, indicating a synergistic interaction. The ∑FBEC  index for gentamicin plus Manuka honey against P. aeruginosa PAO1 biofilms was 0.78–0.82, indicat...

  10. Biodegradation and adsorption of antibiotics in the activated sludge process.

    Science.gov (United States)

    Li, Bing; Zhang, Tong

    2010-05-01

    The removal of 11 antibiotics of 6 classes, that is, two beta-lactams (ampicillin and cefalexin), two sulfonamides (sulfamethoxazole and sulfadiazine), three fluoroquinolones (norfloxacin, ofloxacin, and ciprofloxacin), one tetracyclines (tetracycline), two macorlides (roxithromycin and anhydro-erythromycin), and one others (trimethoprim), in activated sludge process was investigated using two series of batch reactors treating freshwater and saline sewage respectively. At environmental relevant concentrations tested in this study, biodegradation and adsorption were the major removal routes for the target antibiotics, where volatilization and hydrolysis were neglectable. Among the 11 target antibiotics, cefalexin and the two sulfonamides were predominantly removed by biodegradation in both freshwater and saline sewage systems. Ampicillin, norfloxacin, ciprofloxacin, ofloxacin, tetracycline, roxithromycin, and trimethoprim were mainly removed by adsorption. Divalent cations (Ca(2+) and Mg(2+)) in saline sewage significantly decreased the adsorption of the three fluoroquinolones onto activated sludge. These three fluoroquinolones also exhibited certain biodegradability in the saline activated sludge reactor. Erythromycin-H(2)O was persistent in both saline and freshwater systems under the experimental conditions and could not be removed at all. Kinetics study showed that biodegradation of cefalexin, the two sulfonamides and the three fluoroquinolones followed first-order model well (R(2): 0.921-0.997) with the rate constants ranging from 5.2 x 10(-3) to 3.6 x 10(-1) h(-1).

  11. Structure of the phosphotransferase domain of the bifunctional aminoglycoside-resistance enzyme AAC(6′)-Ie-APH(2′′)-Ia

    Science.gov (United States)

    Smith, Clyde A.; Toth, Marta; Bhattacharya, Monolekha; Frase, Hilary; Vakulenko, Sergei B.

    2014-01-01

    The bifunctional acetyltransferase(6′)-Ie-phosphotransfer­ase(2′′)-Ia [AAC(6′)-Ie-APH(2′′)-Ia] is the most important aminoglycoside-resistance enzyme in Gram-positive bacteria, conferring resistance to almost all known aminoglycoside antibiotics in clinical use. Owing to its importance, this enzyme has been the focus of intensive research since its isolation in the mid-1980s but, despite much effort, structural details of AAC(6′)-Ie-APH(2′′)-Ia have remained elusive. The structure of the Mg2GDP complex of the APH(2′′)-Ia domain of the bifunctional enzyme has now been determined at 2.3 Å resolution. The structure of APH(2′′)-Ia is reminiscent of the structures of other aminoglycoside phosphotransferases, having a two-domain architecture with the nucleotide-binding site located at the junction of the two domains. Unlike the previously characterized APH(2′′)-IIa and APH(2′′)-IVa enzymes, which are capable of utilizing both ATP and GTP as the phosphate donors, APH(2′′)-Ia uses GTP exclusively in the phosphorylation of the aminoglycoside antibiotics, and in this regard closely resembles the GTP-dependent APH(2′′)-IIIa enzyme. In APH(2′′)-Ia this GTP selectivity is governed by the presence of a ‘gatekeeper’ residue, Tyr100, the side chain of which projects into the active site and effectively blocks access to the adenine-binding template. Mutation of this tyrosine residue to a less bulky phenylalanine provides better access for ATP to the NTP-binding template and converts APH(2′′)-Ia into a dual-specificity enzyme. PMID:24914967

  12. Association between the Presence of Aminoglycoside-Modifying Enzymes and In Vitro Activity of Gentamicin, Tobramycin, Amikacin, and Plazomicin against Klebsiella pneumoniae Carbapenemase- and Extended-Spectrum-β-Lactamase-Producing Enterobacter Species.

    Science.gov (United States)

    Haidar, Ghady; Alkroud, Ammar; Cheng, Shaoji; Churilla, Travis M; Churilla, Bryce M; Shields, Ryan K; Doi, Yohei; Clancy, Cornelius J; Nguyen, M Hong

    2016-09-01

    We compared the in vitro activities of gentamicin (GEN), tobramycin (TOB), amikacin (AMK), and plazomicin (PLZ) against 13 Enterobacter isolates possessing both Klebsiella pneumoniae carbapenemase and extended-spectrum β-lactamase (KPC+/ESBL+) with activity against 8 KPC+/ESBL-, 6 KPC-/ESBL+, and 38 KPC-/ESBL- isolates. The rates of resistance to GEN and TOB were higher for KPC+/ESBL+ (100% for both) than for KPC+/ESBL- (25% and 38%, respectively), KPC-/ESBL+ (50% and 17%, respectively), and KPC-/ESBL- (0% and 3%, respectively) isolates. KPC+/ESBL+ isolates were more likely than others to possess an aminoglycoside-modifying enzyme (AME) (100% versus 38%, 67%, and 5%; P = 0.007, 0.06, and 1 AME than with ≤1 AME. The presence of at least 2/3 of KPC, SHV, and TEM predicted the presence of AMEs. PLZ MICs against all isolates were ≤4 μg/ml, regardless of KPC/ESBL pattern or the presence of AMEs. In conclusion, GEN and TOB are limited as treatment options against KPC+ and ESBL+ Enterobacter PLZ may represent a valuable addition to the antimicrobial armamentarium. A full understanding of AMEs and other aminoglycoside resistance mechanisms will allow clinicians to incorporate PLZ rationally into treatment regimens. The development of molecular assays that accurately and rapidly predict antimicrobial responses among KPC- and ESBL-producing Enterobacter spp. should be a top research priority. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  13. Natural bizbenzoquinoline derivatives protect zebrafish lateral line sensory hair cells from aminoglycoside toxicity

    Directory of Open Access Journals (Sweden)

    Matthew eKruger

    2016-03-01

    Full Text Available Moderate to severe hearing loss affects 360 million people worldwide and most often results from damage to sensory hair cells. Hair cell damage can result from aging, genetic mutations, excess noise exposure, and certain medications including aminoglycoside antibiotics. Aminoglycosides are effective at treating infections associated with cystic fibrosis and other life-threatening conditions such as sepsis, but cause hearing loss in 20-30% of patients. It is therefore imperative to develop new therapies to combat hearing loss and allow safe use of these potent antibiotics. We approach this drug discovery question using the larval zebrafish lateral line because zebrafish hair cells are structurally and functionally similar to mammalian inner ear hair cells and respond similarly to toxins. We screened a library of 502 natural compounds in order to identify novel hair cell protectants. Our screen identified four bisbenzylisoquinoline derivatives: berbamine, E6 berbamine, hernandezine, and isotetrandrine, each of which robustly protected hair cells from aminoglycoside-induced damage. Using fluorescence microscopy and electrophysiology, we demonstrated that the natural compounds confer protection by reducing antibiotic uptake into hair cells and showed that hair cells remain functional during and after incubation in E6 berbamine. We also determined that these natural compounds do not reduce antibiotic efficacy. Together, these natural compounds represent a novel source of possible otoprotective drugs that may offer therapeutic options for patients receiving aminoglycoside treatment.

  14. UK-18,892: resistance to modification by aminoglycoside-inactivating enzymes.

    Science.gov (United States)

    Andrews, R J; Brammer, K W; Cheeseman, H E; Jevons, S

    1978-12-01

    UK-18,892, a new semisynthetic aminoglycoside, was active against bacteria possessing aminoglycoside-inactivating enzymes, with the exception of some known to possess AAC(6') or AAD(4') enzymes. This activity has been rationalized by using cell-free extracts of bacteria containing known inactivating enzymes, where it was shown that UK-18,892 was not a substrate for the APH(3'), AAD(2''), AAC(3), and AAC(2') enzymes. It was also demonstrated that UK-18,892 protected mice against lethal infections caused by organisms possessing aminoglycoside-inactivating enzymes.

  15. Kinetic and Structural Analysis of Bisubstrate Inhibition of the Salmonella enterica Aminoglycoside 6′-N-Acetyltransferase†,‡

    Science.gov (United States)

    Magalhães, Maria L. B.; Vetting, Matthew W.; Gao, Feng; Freiburger, Lee; Auclair, Karine; Blanchard, John S.

    2011-01-01

    Aminoglycosides are antibacterial compounds that act by binding to the A site of the small 30S bacterial ribosomal subunit and inhibiting protein translation. Clinical resistance to aminoglycosides is generally the result of the expression of enzymes that covalently modify the antibiotic, including phosphorylation, adenylylation, and acetylation. Bisubstrate analogs for the aminoglycoside N-acetyl-transferases are nanomolar inhibitors of Enterococcus faecium AAC(6′)-Ii. However, in the case of the Salmonella enterica aac(6′)-Iy-encoded aminoglycoside N-acetyltransferase, we demonstrate that a series of bisubstrate analogs are only micromolar inhibitors. In contrast to studies with AAC(6′)-Ii, the inhibition constants toward AAC(6′)-Iy are essentially independent of both the identity of the aminoglycoside component of the bisubstrate and the number of carbon atoms that are used to link the CoA and aminoglycoside components. The patterns of inhibition suggest that the CoA portion of the bisubstrate analog can bind to the enzyme–aminoglycoside substrate complex and that the aminoglycoside portion can bind to the enzyme–CoA product complex. However, at the high concentrations of bisubstrate analog used in crystallization experiments, we could crystallize and solve the three-dimensional structure of the enzyme–bisubstrate complex. The structure reveals that both the CoA and aminoglycoside portions bind in essentially the same positions as those previously observed for the enzyme–CoA–ribostamycin complex, with only a modest adjustment to accommodate the “linker”. These results are compared to previous studies of the interaction of similar bisubstrate analogs with other aminoglycoside N-acetyltransferases. PMID:18095712

  16. [Determination of antibiotics using luminescent Escherichia coli and serum].

    Science.gov (United States)

    Vlasova, I I; Asrieli, T V; Gavrilova, E M; Danilov, V S

    2007-01-01

    The methodical bases for detecting antibiotics using a bioluminescent assay and blood serum are briefed. Antibiotics inhibit the luminescence of a genetically engineered Escherichia coli strain. The degree of inhibition depended on the type of antibiotic, its concentration, and the time of cell incubation with antibiotic. The highest cell sensitivity was recorded towards the aminoglycoside antibiotics, which amounted to 85 +/- 10 ng/ml for gentamicin and streptomycin. The sensitivity of this system to a number of antibiotics essentially increased when the cells were previously activated with blood serum. The sensitivity of this method for gentamicin and streptomycin in the presence of blood serum amounted to 2.5 +/- 0.5 ng/ml; for tetracycline, 45 +/- 8 ng/ml. Use of the sera containing specific antibodies to the antibiotic detected provided a high sensitivity of the biosensor tested. Comparison of the luminescences of E. coli cells activated with normal and specific antisera upon incubation with an antibiotic allows the type of antibiotic and its quantitative content in the sample to be determined. Characteristic of the analysis of antibiotics with the help of recombinant E. coli are a high accuracy, sensitivity, specificity, simplicity, and a short time needed for measurement.

  17. Antibiotic activity of Plectranthus ornatus Codd., a Traditional Medicinal Plant.

    Science.gov (United States)

    Nascimento, Fernanda R; Albuquerque, Kamylla R S; Oliveira, Marcos R; Pizziolo, Virginia R; Brasileiro, Beatriz G; Diaz, Gaspar; Diaz, Marisa A N

    2017-01-01

    The dichloromethane extract of Plectranthus ornatus Codd., a tradicional medicinal plant, showed antibiotic activity with minimum inhibitory concentration (MIC) values of 0.4 mg.mL-1 and 100 percent of biofilm inhibition against Staphylococcus aureus strains isolated from animals with mastitis infections. Based on these antibacterial activities, in addition to ethnopharmacological reports from healing men and farmers in Brazil, an herbal soap was produced from this active extract and was tested both in vitro and in vivo. In vivo assays conducted on these herbal soaps led to results similar to those previously conducted with the active extract. These results indicated the great potential of this plant for use as an excipient by preparing herbal antibacterial soaps as an alternative veterinary medicine aimed at controlling bovine mastitis infections on small Brazilian farms.

  18. Antibiotic activity of Plectranthus ornatus Codd., a Traditional Medicinal Plant

    Directory of Open Access Journals (Sweden)

    FERNANDA R. NASCIMENTO

    2017-10-01

    Full Text Available ABSTRACT The dichloromethane extract of Plectranthus ornatus Codd., a tradicional medicinal plant, showed antibiotic activity with minimum inhibitory concentration (MIC values of 0.4 mg.mL-1 and 100 percent of biofilm inhibition against Staphylococcus aureus strains isolated from animals with mastitis infections. Based on these antibacterial activities, in addition to ethnopharmacological reports from healing men and farmers in Brazil, an herbal soap was produced from this active extract and was tested both in vitro and in vivo. In vivo assays conducted on these herbal soaps led to results similar to those previously conducted with the active extract. These results indicated the great potential of this plant for use as an excipient by preparing herbal antibacterial soaps as an alternative veterinary medicine aimed at controlling bovine mastitis infections on small Brazilian farms.

  19. Megalin-targeted enhanced transfection efficiency in cultured human HK-2 renal tubular proximal cells using aminoglycoside-carboxyalkyl- polyethylenimine -containing nanoplexes.

    Science.gov (United States)

    Oroojalian, Fatemeh; Rezayan, Ali Hossein; Shier, Wayne Thomas; Abnous, Khalil; Ramezani, Mohammad

    2017-05-15

    Non-viral vectors are of interest as therapeutic gene delivery agents in gene therapy, because they are simple to prepare, easy to modify and have definable safety profiles compared to viral vectors. The potential of gene therapy in the treatment of renal diseases is limited by a lack of effective kidney-targeted gene delivery systems. Aminoglycoside antibiotics gentamicin and neomycin were connected by amide linkages to carboxyl groups on carboxyalkylated-PEI 25 (25kDa PEI) or carboxyalkylated-PEI 10 (10kDa PEI). Aminoglycoside-carboxyalkylated-PEI conjugates were characterized with respect to size, surface charge density, DNA condensation ability, and buffering capacity. Polyplexes prepared by electrostatic interaction between aminoglycoside-carboxyalkylated-PEIs and enhanced green fluorescent protein-expressing (EGFP) plasmid DNA had appropriate nano-scale size (143-173nm). Their targeting potential was investigated in cultured HK-2 immortalized human cortex/proximal tubule kidney epithelial cells, which expresses megalin, a scavenger receptor that mediates endocytosis of a diverse group of ligands, including aminoglycoside antibiotics. Aminoglycoside-carboxyalkylated-PEIs significantly increased EGFP gene transfection efficiency in HK-2 cells by ∼13-fold for aminoglycoside-carboxyalkylated-PEI 25 and ∼7-fold increase for aminoglycoside-carboxyalkylated-PEI 10 relative to the corresponding PEIs without aminoglycosides. The transfection efficiency of polyplexes was dependent on the weight ratio of aminoglycoside-containing ligand in the carrier. In the presence of a range of concentrations of human serum albumin, which competes for megalin binding, aminoglycoside-carboxyalkylated-PEI-mediated transfection was reduced to background levels. These results suggest that aminoglycoside-carboxyalkylated-PEI polyplexes can target megalin-expressing kidney-derived cells in vitro resulting in improved transfection efficiency with low cytotoxicity. Copyright © 2017

  20. Purification, Crystallization And Preliminary X-Ray Analysis of Aminoglycoside-2 ''-Phosphotransferase-Ic [APH(2 '')-Ic] From Enterococcus Gallinarum

    Energy Technology Data Exchange (ETDEWEB)

    Byrnes, L.J.; /SLAC, SSRL; Badarau, A.; Vakulenko, S.B.; /Notre Dame U.; Smith, C.A.; /SLAC, SSRL

    2009-04-30

    Bacterial resistance to aminoglycoside antibiotics is primarily the result of deactivation of the drugs. Three families of enzymes are responsible for this activity, with one such family being the aminoglycoside phosphotransferases (APHs). The gene encoding one of these enzymes, aminoglycoside-2{double_prime}-phosphotransferase-Ic [APH(2{double_prime})-Ic] from Enterococcus gallinarum, has been cloned and the wild-type protein (comprising 308 amino-acid residues) and three mutants that showed elevated minimum inhibitory concentrations towards gentamicin (F108L, H258L and a double mutant F108L/H258L) were expressed in Escherichia coli and subsequently purified. All APH(2{double_prime})-Ic variants were crystallized in the presence of 14-20%(w/v) PEG 4000, 0.25 M MgCl{sub 2}, 0.1 M Tris-HCl pH 8.5 and 1 mM Mg{sub 2}GTP. The crystals belong to the monoclinic space group C2, with one molecule in the asymmetric unit. The approximate unit-cell parameters are a = 82.4, b = 54.2, c = 77.0 {angstrom}, {beta} = 108.8{sup o}. X-ray diffraction data were collected to approximately 2.15 {angstrom} resolution from an F108L crystal at beamline BL9-2 at SSRL, Stanford, California, USA.

  1. Study of the Interference between Plectranthus Species Essential Oils from Brazil and Aminoglycosides

    Directory of Open Access Journals (Sweden)

    Fabíola Fernandes Galvão Rodrigues

    2013-01-01

    Full Text Available Plectranthus is one of the most representative genera of Lamiaceae family. In this study, the essential oils from Plectranthus amboinicus, Plectranthus ornatus, and Plectranthus barbatus were investigated for their chemical composition and antimicrobial and modulatory activities. The major components found were carvacrol (54.4%—P. amboinicus and eugenol (22.9%—P. ornatus e 25.1%—P. barbatus. In vitro antimicrobial activity was conducted against Escherichia coli, Proteus vulgaris, Bacillus cereus, Pseudomonas aeruginosa, Staphylococcus aureus, and Staphylococcus aureus (multiresistant using microdilution method. The results of bioassay showed that all strains were sensitive to the oils, except P. aeruginosa that was resistant to P. amboinicus and P. ornatus. A synergistic effect of all essential oils combined with the aminoglycosides was demonstrated. These results show that P. amboinicus, P. ornatus, and P. barbatus inhibit the growth of pathogenic microorganism, and besides this they present antibiotic modifying activity, providing a new perspective against the problem of bacterial resistance to antibiotics.

  2. Detection of antibiotics residues in meat of reformed and marketed ...

    African Journals Online (AJOL)

    Results showed that farmers use eight families of antibiotics: aminoglycosides, diaminopyridines, macrolides, polypeptides, quinolones second and third generation, sulfonamides and tetracyclines. Residues of tetracyclines and aminoglycosides were found only in Abomey-Calavi town with respective proportions of 25.71 ...

  3. Clinical Pharmacokinetics of Penicillins, Cephalosporins and Aminoglycosides in the Neonate: A Review

    Directory of Open Access Journals (Sweden)

    Gian Maria Pacifici

    2010-08-01

    Full Text Available Bacterial infections are common in the neonates and are a major cause of morbidity and mortality. Sixty percent of preterm infants admitted to neonatal intensive care units received at least one antibiotic during the first week of life. Penicillins, aminoglycosides and cephalosporins comprised 53, 43 and 16%, respectively. Kinetic parameters such as the half-life (t1/2, clearance (Cl, and volume of distribution (Vd change with development, so the kinetics of penicillins, cephalosporins and aminoglycosides need to be studied in order to optimise therapy with these drugs. The aim of this study is to review the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate in a single article in order to provide a critical analysis of the literature and thus provide a useful tool in the hands of physicians. The bibliographic search was performed electronically using PubMed, as the search engine, until February 2nd, 2010. Medline search terms were as follows: pharmacokinetics AND (penicillins OR cephalosporins OR aminoglycosides AND infant, newborn, limiting to humans. Penicillins, cephalosporins and aminoglycosides are fairly water soluble and are mainly eliminated by the kidneys. The maturation of the kidneys governs the pharmacokinetics of penicillins, cephalosporins and aminoglycosides in the neonate. The renal excretory function is reduced in preterms compared to term infants and Cl of these drugs is reduced in premature infants. Gestational and postnatal ages are important factors in the maturation of the neonate and, as these ages proceed, Cl of penicillins, cephalosporins and aminoglycosides increases. Cl and t1/2 are influenced by development and this must be taken into consideration when planning a dosage regimen with these drugs. More pharmacokinetic studies are required to ensure that the dose recommended for the treatment of sepsis in the neonate is evidence based.

  4. Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Nielsen Lene N

    2012-08-01

    Full Text Available Abstract Background The aim of this study was to investigate the effect of various classes of clinically relevant antibiotics at sub-lethal concentrations on virulence gene expression and biofilm formation in Staphylococcus aureus. Findings LacZ promoter fusions of genes related to staphylococcal virulence were used to monitor the effects of antibiotics on gene expression in a disc diffusion assay. The selected genes were hla and spa encoding α-hemolysin and Protein A, respectively and RNAIII, the effector molecule of the agr quorum sensing system. The results were confirmed by quantitative real-time PCR. Additionally, we monitored the effect of subinhibitory concentrations of antibiotics on the ability of S. aureus to form biofilm in a microtiter plate assay. The results show that sub-lethal antibiotic concentrations diversely modulate expression of RNAIII, hla and spa. Consistently, expression of all three genes were repressed by aminoglycosides and induced by fluoroquinolones and penicillins. In contrast, the β-lactam sub-group cephalosporins enhanced expression of RNAIII and hla but diversely affected expression of spa. The compounds cefalotin, cefamandole, cefoxitin, ceftazidime and cefixine were found to up-regulate spa, while down-regulation was observed for cefuroxime, cefotaxime and cefepime. Interestingly, biofilm assays demonstrated that the spa-inducing cefalotin resulted in less biofilm formation compared to the spa-repressing cefotaxime. Conclusions We find that independently of the cephalosporin generation, cephalosporins oppositely regulate spa expression and biofilm formation. Repression of spa expression correlates with the presence of a distinct methyloxime group while induction correlates with an acidic substituted oxime group. As cephalosporines target the cell wall penicillin binding proteins we speculate that subtle differences in this interaction fine-tunes spa expression independently of agr.

  5. Assessment of aminoglycoside-induced hearing impairment in hospitalized neonates by TEOAE.

    Science.gov (United States)

    Naeimi, Mohammad; Maamouri, Gholamali; Boskabadi, Hassan; Golparvar, Sadegh; Taleh, Mohamadreza; Esmaeeli, Habib; Khademi, Javad

    2009-12-01

    Aminoglycosides, as potent bactericidal antibiotics against aerobic gram-negative infections, is still widely used, especially in NICU patients, despite their known potential ototoxic effects. To evaluate the potential of transient evoked otoacoustic emissions (TEOAEs) in early identification of decreased hearing sensitivity in hospitalized neonates receiving aminoglycosides for severe gram-negative infections. Fifty (50) neonates treated with intravenous gentamicin (5 mg/kg/day) or amikacin (15 mg/kg/day) were tested with TEOAE in the beginning and the end of aminoglycoside therapeutic course. There were 23 males and 27 females, ranging from 29 to 40 weeks (mean: 36 weeks). The treatment duration was 3-30 days (in 26 neonates up to 7 days - group A, and in 24 neonates higher than 7 days - group B). In group A, no statistically significant difference in the mean response level was found between the onset and the end of treatment course (p > 0.001). In group B, a statistically significant difference in the mean response level was found between the onset and the end of treatment course, especially at high frequency region (p < 0.001). TEOAE is sensitive enough to detect early aminoglycoside ototoxicity. As this test is simple to perform, non-invasive and reliable, so we suggest that TEOAE test should be performed in NICU as routine for monitoring cochlear function to prevent permanent hearing loss especially in those who are receiving aminoglycoside for more than 7 days.

  6. The antibiotic activity of some Brazilian medicinal plants

    Directory of Open Access Journals (Sweden)

    Maria R. Ferreira de Lima

    Full Text Available The antibiotic activities of the ethanol extracts from 16 species of plants used in Brazilian folk medicine have been determined against Staphylococcus aureus, Micrococcus flavus, Bacillus cereus, B. subtilis, Salmonella enteretidis, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Serratia marcescens, Mycobacterium phlei, M. smegmatis and M. fortuitum, and the yeasts Candida albicans and C. krusei. Among 32 extracts assayed, only those from Lafoensia pacari and Pterodon polygalaeflorus showed activity against the bacterial strains, and none were active against the yeasts. The ethanolic extract from the leaves of L. pacari showed minimum inhibitory concentration (MIC values of 312.5 to 2500, 250, 625 and 1250 mg/mL, respectively, against eight different Gram-positive strains of Staphylococcus aureus, the Gram-negative Proteus mirabilis and the acid-fast bacilli Mycobacterium phlei, M. fortuitum and M. smegmatis. The ethanolic extract from the stem of L. pacari showed an MIC value of 625 mg/mL against S. aureus. Chemical analysis revealed that the crude extracts contained tannins, steroids, phenols, flavonoids, triterpenes and saponins: the activities were sufficiently high to present the possibility of future identification of the active components by bioassay-guided fractionation and purification.

  7. Phytochemical Prospection and Modulation of Antibiotic Activity In Vitro by Lippia origanoides H.B.K. in Methicillin Resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Humberto Medeiros Barreto

    2014-01-01

    Full Text Available The Lippia origanoides H.B.K. ethanol extract (LOEE and hexane (LOHEX, dichloromethane (LODCM, and ethyl acetate (LOEA fractions were tested for their antimicrobial activity alone or in combination with antibiotics against a methicillin resistant Staphylococcus aureus (MRSA strain. The natural products did not show antimicrobial activity against multidrug resistant strain at the clinically significant concentrations tested. However, a modulatory effect in the antibacterial activity of the neomycin and amikacin was verified when LOEE, LOHEX and LODCM were added to the growth medium at subinhibitory concentrations. A similar modulation was found when the natural products were changed for chlorpromazine, an inhibitor of bacterial efflux pumps, suggesting the involvement of resistance mediated by efflux system in the MRSA tested. The fractions LOHEX and LODCM showed a modulatory activity bigger than their majority compounds (carvacrol, thymol, and naringenin, indicating that this activity is not due to their majority compounds only, but it is probably due to a synergism between their chemical components. These results indicate that L. origanoides H.B.K. can be a source of phytochemicals able to modify the phenotype of resistance to aminoglycosides in MRSA.

  8. Proliferation of Antibiotic-Producing Bacteria and Concomitant Antibiotic Production as the Basis for the Antibiotic Activity of Jordan's Red Soils▿

    Science.gov (United States)

    Falkinham, Joseph O.; Wall, Thomas E.; Tanner, Justin R.; Tawaha, Khaled; Alali, Feras Q.; Li, Chen; Oberlies, Nicholas H.

    2009-01-01

    Anecdotes, both historical and recent, recount the curing of skin infections, including diaper rash, by using red soils from the Hashemite Kingdom of Jordan. Following inoculation of red soils isolated from geographically separate areas of Jordan, Micrococcus luteus and Staphylococcus aureus were rapidly killed. Over the 3-week incubation period, the number of specific types of antibiotic-producing bacteria increased, and high antimicrobial activity (MIC, ∼10 μg/ml) was observed in methanol extracts of the inoculated red soils. Antibiotic-producing microorganisms whose numbers increased during incubation included actinomycetes, Lysobacter spp., and Bacillus spp. The actinomycetes produced actinomycin C2 and actinomycin C3. No myxobacteria or lytic bacteriophages with activity against either M. luteus or S. aureus were detected in either soil before or after inoculation and incubation. Although protozoa and amoebae were detected in the soils, the numbers were low and did not increase over the incubation period. These results suggest that the antibiotic activity of Jordan's red soils is due to the proliferation of antibiotic-producing bacteria. PMID:19286796

  9. Lack of antimicrobial bactericidal activity in Mycobacterium abscessus.

    Science.gov (United States)

    Maurer, Florian P; Bruderer, Vera L; Ritter, Claudia; Castelberg, Claudio; Bloemberg, Guido V; Böttger, Erik C

    2014-07-01

    Antibiotic therapy of infections caused by the emerging pathogen Mycobacterium abscessus is challenging due to the organism's natural resistance toward most clinically available antimicrobials. We investigated the bactericidal activity of antibiotics commonly administered in M. abscessus infections in order to better understand the poor therapeutic outcome. Time-kill curves were generated for clinical M. abscessus isolates, Mycobacterium smegmatis, and Escherichia coli by using antibiotics commonly categorized as bactericidal (amikacin and moxifloxacin) or bacteriostatic (tigecycline and linezolid). In addition, the impact of aminoglycoside-modifying enzymes on the mode of action of substrate and nonsubstrate aminoglycosides was studied by using M. smegmatis as a model organism. While amikacin and moxifloxacin were bactericidal against E. coli, none of the tested compounds showed bactericidal activity against M. abscessus. Further mechanistic investigations of the mode of action of aminoglycosides in M. smegmatis revealed that the bactericidal activity of tobramycin and gentamicin was restored by disruption of the chromosomal aac(2') gene in the mycobacterial genome. The lack of bactericidal antibiotics in currently recommended treatment regimens provides a reasonable explanation for the poor therapeutic outcome in M. abscessus infection. Our findings suggest that chromosomally encoded drug-modifying enzymes play an important role in the lack of aminoglycoside bactericidal activity against rapidly growing mycobacteria. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  10. Crystallization and preliminary crystallographic analysis of an aminoglycoside kinase from Legionella pneumophila

    International Nuclear Information System (INIS)

    Lemke, Christopher T.; Hwang, Jiyoung; Xiong, Bing; Cianciotto, Nicholas P.; Berghuis, Albert M.

    2005-01-01

    Two crystal forms of the antibiotic resistance enzyme APH(9)-Ia from L. pneumophila are reported. 9-Aminoglycoside phosphotransferase type Ia [APH(9)-Ia] is a resistance factor in Legionella pneuemophila, the causative agent of legionnaires’ disease. It is responsible for providing intrinsic resistance to the antibiotic spectinomycin. APH(9)-Ia phosphorylates one of the hydroxyl moieties of spectinomycin in an ATP-dependent manner, abolishing the antibiotic properties of this drug. Here, the crystallization and preliminary X-ray studies of this enzyme in two crystal forms is reported. One of the these crystal forms provides diffraction data to a resolution of 1.7 Å

  11. Molecular Identification of Streptomyces producing antibiotics and their antimicrobial activities

    Directory of Open Access Journals (Sweden)

    Latifa A. Al_husnan

    2016-12-01

    Full Text Available Five strains of Streptomyces, namely S, N, W, E and C (designations should be mentioned in detail here isolated from the rhizosphere soil cultivated with palm Alajua (date, pressed dates, AlMedina city, Saudi Arabia, were induced to produce antibiotics. Antimicrobial activities were determined on solid medium supplemented with starch. The detection was based on the formation of transparent zones around colonies. The results indicated that isolates had antibacterial activities against Staphylococcus aureus, Bacillus cereus, B. subtilis, Pseudomonas aeruginosa and also showed antifungal activity against Candida albicans and Aspergillus niger. DNA extracted from five isolates was used as template for 16s rDNA gene amplification. The expected PCR size was 1.5 kbp;1.6 kbp; 1.25 kbp; 1.25kbp and 1.0 k bp for S, N, W, E and C isolates respectively using universal 16s rDNA gene primers using direct PCR. The isolates varied morphologically on the basis of spore color, aerial and substrate mycelium formation, and production of diffusible pigment. Isolates were tested under a microscope by using slide culture technique. The results indicate that the soil of this region is source of Streptomyces having antibacterial and antifungal activity and thus better utilization of these microorganisms as biological control agents.

  12. Functional characterization of bacteria isolated from ancient arctic soil exposes diverse resistance mechanisms to modern antibiotics.

    Directory of Open Access Journals (Sweden)

    Gabriel G Perron

    Full Text Available Using functional metagenomics to study the resistomes of bacterial communities isolated from different layers of the Canadian high Arctic permafrost, we show that microbial communities harbored diverse resistance mechanisms at least 5,000 years ago. Among bacteria sampled from the ancient layers of a permafrost core, we isolated eight genes conferring clinical levels of resistance against aminoglycoside, β-lactam and tetracycline antibiotics that are naturally produced by microorganisms. Among these resistance genes, four also conferred resistance against amikacin, a modern semi-synthetic antibiotic that does not naturally occur in microorganisms. In bacteria sampled from the overlaying active layer, we isolated ten different genes conferring resistance to all six antibiotics tested in this study, including aminoglycoside, β-lactam and tetracycline variants that are naturally produced by microorganisms as well as semi-synthetic variants produced in the laboratory. On average, we found that resistance genes found in permafrost bacteria conferred lower levels of resistance against clinically relevant antibiotics than resistance genes sampled from the active layer. Our results demonstrate that antibiotic resistance genes were functionally diverse prior to the anthropogenic use of antibiotics, contributing to the evolution of natural reservoirs of resistance genes.

  13. Functional characterization of bacteria isolated from ancient arctic soil exposes diverse resistance mechanisms to modern antibiotics.

    Science.gov (United States)

    Perron, Gabriel G; Whyte, Lyle; Turnbaugh, Peter J; Goordial, Jacqueline; Hanage, William P; Dantas, Gautam; Desai, Michael M

    2015-01-01

    Using functional metagenomics to study the resistomes of bacterial communities isolated from different layers of the Canadian high Arctic permafrost, we show that microbial communities harbored diverse resistance mechanisms at least 5,000 years ago. Among bacteria sampled from the ancient layers of a permafrost core, we isolated eight genes conferring clinical levels of resistance against aminoglycoside, β-lactam and tetracycline antibiotics that are naturally produced by microorganisms. Among these resistance genes, four also conferred resistance against amikacin, a modern semi-synthetic antibiotic that does not naturally occur in microorganisms. In bacteria sampled from the overlaying active layer, we isolated ten different genes conferring resistance to all six antibiotics tested in this study, including aminoglycoside, β-lactam and tetracycline variants that are naturally produced by microorganisms as well as semi-synthetic variants produced in the laboratory. On average, we found that resistance genes found in permafrost bacteria conferred lower levels of resistance against clinically relevant antibiotics than resistance genes sampled from the active layer. Our results demonstrate that antibiotic resistance genes were functionally diverse prior to the anthropogenic use of antibiotics, contributing to the evolution of natural reservoirs of resistance genes.

  14. Functional Characterization of Bacteria Isolated from Ancient Arctic Soil Exposes Diverse Resistance Mechanisms to Modern Antibiotics

    Science.gov (United States)

    Perron, Gabriel G.; Whyte, Lyle; Turnbaugh, Peter J.; Goordial, Jacqueline; Hanage, William P.; Dantas, Gautam; Desai, Michael M.

    2015-01-01

    Using functional metagenomics to study the resistomes of bacterial communities isolated from different layers of the Canadian high Arctic permafrost, we show that microbial communities harbored diverse resistance mechanisms at least 5,000 years ago. Among bacteria sampled from the ancient layers of a permafrost core, we isolated eight genes conferring clinical levels of resistance against aminoglycoside, β-lactam and tetracycline antibiotics that are naturally produced by microorganisms. Among these resistance genes, four also conferred resistance against amikacin, a modern semi-synthetic antibiotic that does not naturally occur in microorganisms. In bacteria sampled from the overlaying active layer, we isolated ten different genes conferring resistance to all six antibiotics tested in this study, including aminoglycoside, β-lactam and tetracycline variants that are naturally produced by microorganisms as well as semi-synthetic variants produced in the laboratory. On average, we found that resistance genes found in permafrost bacteria conferred lower levels of resistance against clinically relevant antibiotics than resistance genes sampled from the active layer. Our results demonstrate that antibiotic resistance genes were functionally diverse prior to the anthropogenic use of antibiotics, contributing to the evolution of natural reservoirs of resistance genes. PMID:25807523

  15. Activation of the Cryptic aac(6′)-Iy Aminoglycoside Resistance Gene of Salmonella by a Chromosomal Deletion Generating a Transcriptional Fusion

    Science.gov (United States)

    Magnet, Sophie; Courvalin, Patrice; Lambert, Thierry

    1999-01-01

    Salmonella enterica subsp. enterica serotype Enteritidis BM4361 and BM4362 were isolated from the same patient. BM4361 was susceptible to aminoglycosides, whereas BM4362 was resistant to tobramycin owing to synthesis of a 6′-N-acetyltransferase type I [AAC(6′)-I]. Comparative analysis of nucleotide sequences, pulsed-field gel electrophoresis patterns, and Southern hybridizations indicated that the chromosomal aac(6′)-Iy genes for the enzyme in both strains were identical and that BM4362 derived from BM4361 following a ca. 60-kb deletion that occurred 1.5 kb upstream from the resistance gene. Northern hybridizations showed that aac(6′)-Iy was silent in BM4361 and highly expressed in BM4362 due to a transcriptional fusion. Primer extension mapping identified the transcriptional start site for aac(6′)-Iy in BM4362: 5 bp downstream from the promoter of the nmpC gene. Study of the distribution of aac(6′)-Iy by PCR and Southern hybridization with a specific probe indicated that the gene, although not found in S. enterica subsp. arizonae, was specific for Salmonella. In this bacterial genus, aac(6′)-Iy was located downstream from a cluster of seven open reading frames analogous to an Escherichia coli locus that encodes enzymes putatively involved in carbohydrate transport or metabolism. This genomic environment suggests a role in the catabolism of a specific sugar for AAC(6′)-Iy in Salmonella. PMID:10542165

  16. A New Twist to the Kirby-Bauer Antibiotic Susceptibility Test Activity?Increasing Antibiotic Sensitivity of Pseudomonas fluorescens through Thermal Stress

    OpenAIRE

    Gerbig, Donald G.; Engohang-Ndong, Jean; Aubihl, Heather

    2013-01-01

    Antibiotic sensitivity and the effect of temperature on microbial growth are two standard laboratory activities found in most microbial laboratory manuals. We have found a novel way to combine the two activities to demonstrate how temperature can influence antibiotic sensitivity using a standard incubator in instructional laboratory settings. This activity reinforces the important concepts of microbial growth and temperature along with Kirby-Bauer antibiotic susceptibility testing. We found t...

  17. Deoxyribonucleoside kinases activate nucleoside antibiotics in severely pathogenic bacteria

    DEFF Research Database (Denmark)

    Sandrini, Michael; Shannon, O.; Clausen, A.R.

    2007-01-01

    Common bacterial pathogens are becoming progressively more resistant to traditional antibiotics, representing a major public-health crisis. Therefore, there is a need for a variety of antibiotics with alternative modes of action. In our study, several nucleoside analogs were tested against...

  18. Antibiotic Activity Assessment of Bacterial Strains Isolated from Urine ...

    African Journals Online (AJOL)

    Urinary tract infections (UTI) are common worldwide and affect all sexes and age groups. An estimated 20% or more of the female population suffers from some form of UTIs in their lifetime. Although antibiotics are the first choice of treatment for many urinary tract infections, antibiotic-resistant strains of bacterial species ...

  19. Sweet antibiotics – the role of glycosidic residues in antibiotic and antitumor activity and their randomization

    Czech Academy of Sciences Publication Activity Database

    Křen, Vladimír; Řezanka, Tomáš

    2008-01-01

    Roč. 32, č. 5 (2008), s. 858-889 ISSN 0168-6445 R&D Projects: GA MŠk(CZ) LC06010; GA AV ČR IAA400200503 Institutional research plan: CEZ:AV0Z50200510 Keywords : glycosides * sweet antibiotics * aglycone Subject RIV: CE - Biochemistry Impact factor: 7.963, year: 2008

  20. d-Tubocurarine and Berbamine: Alkaloids That Are Permeant Blockers of the Hair Cell's Mechano-Electrical Transducer Channel and Protect from Aminoglycoside Toxicity

    NARCIS (Netherlands)

    Kirkwood, Nerissa K.; Derudas, Marco; Kenyon, Emma J; Huckvale, Rosemary; van Netten, Sietse; Ward, Simon; Richardson, Guy P; Kros, Corne J

    2017-01-01

    Aminoglycoside antibiotics are widely used for the treatment of life-threatening bacterial infections, but cause permanent hearing loss in a substantial proportion of treated patients. The sensory hair cells of the inner ear are damaged following entry of these antibiotics via the mechano-electrical

  1. Post treatment of antibiotic wastewater by adsorption on activated carbon

    Science.gov (United States)

    Mullai, P.; Rajesh, V.

    2018-02-01

    The most common method of treating industrial wastewater involves biomethanation in anaerobic digesters. This biological treatment process is ineffective in color removal and it requires post-treatment methods. The color is the first contaminant in wastewater which affects the water bodies in several ways. As the anaerobically digested antibiotic wastewater was found with color, an attempt was made to remove color using granulated activated carbon as an adsorbent. Experiments were carried out in batch reactors to find out the color removal efficiency of the wastewater at four different dosages such as 25, 50, 75 and 100 mg of adsorbent material at each of the four different initial concentrations of effluent like 1956, 1450, 1251 and 1040 mg COD/L. The steady state values of color removal efficiencies were 96.6, 97.64, 98.64 and 99.63%, respectively, using 100 mg of activated carbon under shaking condition at the end of the 120th min. The effect of contact time on the percentage of color removal was also studied. It was observed that the adsorption of effluent obtained equilibrium at 120 minutes. The equilibrium data fitted well with the Langmuir and Freundlich isotherms.

  2. Plasmid metagenome reveals high levels of antibiotic resistance genes and mobile genetic elements in activated sludge

    OpenAIRE

    Zhang, T; Zhang, XX; Ye, L

    2011-01-01

    The overuse or misuse of antibiotics has accelerated antibiotic resistance, creating a major challenge for the public health in the world. Sewage treatment plants (STPs) are considered as important reservoirs for antibiotic resistance genes (ARGs) and activated sludge characterized with high microbial density and diversity facilitates ARG horizontal gene transfer (HGT) via mobile genetic elements (MGEs). However, little is known regarding the pool of ARGs and MGEs in sludge microbiome. In thi...

  3. Accuracy of genetic code translation and its orthogonal corruption by aminoglycosides and Mg2+ ions.

    Science.gov (United States)

    Zhang, Jingji; Pavlov, Michael Y; Ehrenberg, Måns

    2018-02-16

    We studied the effects of aminoglycosides and changing Mg2+ ion concentration on the accuracy of initial codon selection by aminoacyl-tRNA in ternary complex with elongation factor Tu and GTP (T3) on mRNA programmed ribosomes. Aminoglycosides decrease the accuracy by changing the equilibrium constants of 'monitoring bases' A1492, A1493 and G530 in 16S rRNA in favor of their 'activated' state by large, aminoglycoside-specific factors, which are the same for cognate and near-cognate codons. Increasing Mg2+ concentration decreases the accuracy by slowing dissociation of T3 from its initial codon- and aminoglycoside-independent binding state on the ribosome. The distinct accuracy-corrupting mechanisms for aminoglycosides and Mg2+ ions prompted us to re-interpret previous biochemical experiments and functional implications of existing high resolution ribosome structures. We estimate the upper thermodynamic limit to the accuracy, the 'intrinsic selectivity' of the ribosome. We conclude that aminoglycosides do not alter the intrinsic selectivity but reduce the fraction of it that is expressed as the accuracy of initial selection. We suggest that induced fit increases the accuracy and speed of codon reading at unaltered intrinsic selectivity of the ribosome.

  4. Functional characterization of MexXY and OpmG in aminoglycoside efflux in Pseudomonas aeruginosa.

    Science.gov (United States)

    Chuanchuen, Rungtip; Wannaprasat, Wechsiri; Schweizer, Herbert P

    2008-01-01

    MexXY is an active efflux system that contributes to intrinsic resistance to aminoglycosides in Pseudomonas aeruginosa. MexXY can function in combination with OprM in aminoglycoside efflux but may also functionally associate with another as yet unidentified outer membrane channel. The possible role of OpmG as a third component of MexXY in aminoglycoside efflux was investigated by construction of unmarked opmG mutants. Loss of OpmG did not have any impact on minimum inhibitory concentrations for aminoglycosides regardless of the presence of oprM, indicating that MexXY does not interact with OpmG in aminoglycoside efflux. In a clinical isolate PAJ010, (mexXY) enhanced streptomycin susceptibility but neither oprM nor opmG could, suggesting that MexXY functionally associates with an unidentified outer membrane protein for aminoglycoside efflux. Expression of an opmG-lacZ transcriptional fusion revealed that OpmG expression was neither constitutive nor inducible by gentamicin. Growth rates of wildtype P. aeruginosa and opmG mutant derivatives were not different, indicating that expression of opmG is not essential for P. aeruginosa growth.

  5. Berberine Is a Novel Type Efflux Inhibitor Which Attenuates the MexXY-Mediated Aminoglycoside Resistance in Pseudomonas aeruginosa.

    Science.gov (United States)

    Morita, Yuji; Nakashima, Ken-Ichi; Nishino, Kunihiko; Kotani, Kenta; Tomida, Junko; Inoue, Makoto; Kawamura, Yoshiaki

    2016-01-01

    The emergence and spread of multidrug-resistant P. aeruginosa infections is of great concern, as very few agents are effective against strains of this species. Methanolic extracts from the Coptidis Rhizoma (the rhizomes of Coptis japonica var. major Satake) or Phellodendri Cortex (the bark of Phellodendron chinense Schneider) markedly reduced resistance to anti-pseudomonal aminoglycosides (e.g., amikacin) in multidrug-resistant P. aeruginosa strains. Berberine, the most abundant benzylisoquinoline alkaloid in the two extracts, reduced aminoglycoside resistance of P. aeruginosa via a mechanism that required the MexXY multidrug efflux system; berberine also reduced aminoglycoside MICs in Achromobacter xylosoxidans and Burkholderia cepacia, two species that harbor intrinsic multidrug efflux systems very similar to the MexXY. Furthermore this compound inhibited MexXY-dependent antibiotic resistance of other classes including cephalosporins (cefepime), macrolides (erythromycin), and lincosamides (lincomycin) demonstrated using a pseudomonad lacking the four other major Mex pumps. Although phenylalanine-arginine beta-naphthylamide (PAβN), a well-known efflux inhibitor, antagonized aminoglycoside in a MexXY-dependent manner, a lower concentration of berberine was sufficient to reduce amikacin resistance of P. aeruginosa in the presence of PAβN. Moreover, berberine enhanced the synergistic effects of amikacin and piperacillin (and vice versa) in multidrug-resistant P. aeruginosa strains. Thus, berberine appears to be a novel type inhibitor of the MexXY-dependent aminoglycoside efflux in P. aeruginosa. As aminoglycosides are molecules of choice to treat severe infections the clinical impact is potentially important.

  6. Linking the Effect of Antibiotics on Partial-Nitritation Biofilters: Performance, Microbial Communities and Microbial Activities

    Directory of Open Access Journals (Sweden)

    Alejandro Gonzalez-Martinez

    2018-02-01

    Full Text Available The emergence and spread of antibiotics resistance in wastewater treatment systems have been pointed as a major environmental health problem. Nevertheless, research about adaptation and antibiotics resistance gain in wastewater treatment systems subjected to antibiotics has not been successfully developed considering bioreactor performance, microbial community dynamics and microbial activity dynamics at the same time. To observe this in autotrophic nitrogen removal systems, a partial-nitritation biofilter was subjected to a continuous loading of antibiotics mix of azithromycin, norfloxacin, trimethoprim, and sulfamethoxazole. The effect of the antibiotics mix over the performance, bacterial communities and bacterial activity in the system was evaluated. The addition of antibiotics caused a drop of ammonium oxidation efficiency (from 50 to 5% and of biomass concentration in the bioreactor, which was coupled to the loss of ammonium oxidizing bacteria Nitrosomonas in the bacterial community from 40 to 3%. Biomass in the partial nitritation biofilter experienced a sharp decrease of about 80% due to antibiotics loading, but the biomass adapted and experienced a growth by stabilization under antibiotics feeding. During the experiment several bacterial genera appeared, such as Alcaligenes, Paracoccus, and Acidovorax, clearly dominating the bacterial community with >20% relative abundance. The system reached around 30% ammonium oxidation efficiency after adaptation to antibiotics, but no effluent nitrite was found, suggesting that dominant antibiotics-resistant phylotypes could be involved in nitrification–denitrification metabolisms. The activity of ammonium oxidation measured as amoA and hao gene expression dropped a 98.25% and 99.21%, respectively, comparing the system before and after the addition of antibiotics. On the other hand, denitrifying activity increased as observed by higher expression of nir and nos genes (83.14% and 252

  7. Characterization of Aminoglycoside Resistance and Virulence Genes among Enterococcus spp. Isolated from a Hospital in China

    Directory of Open Access Journals (Sweden)

    Wanxiang Li

    2015-03-01

    Full Text Available This study investigated the aminoglycoside resistance phenotypes and genotypes, as well as the prevalence of virulence genes, in Enterococcus species isolated from clinical patients in China. A total of 160 enterococcal isolates from various clinical samples collected from September 2013 to July 2014 were identified to the species level using the VITEK-2 COMPACT system. The antimicrobial susceptibilities of the identified Enterococcus strains were determined by the Kirby-Bauer (K-B disc diffusion method. PCR-based assays were used to detect the aminoglycoside resistance and virulence genes in all enterococcal isolates. Of 160 Enterococcus isolates, 105 were identified as E. faecium, 35 as E. faecalis, and 20 isolates were classified as “other” Enterococcus species. High-level aminoglycoside resistance (HLAR for gentamicin, streptomycin, and both antibiotics was identified in 58.8, 50, and 34.4% of strains, respectively. The most common virulence gene (50.6% of isolates was efaA, followed by asa1 (28.8%. The most prevalent aminoglycoside resistance genes were aac(6'-Ie-aph(2'', aph(2'-Id, aph(3'-IIIa, and ant(6'-Ia, present in 49.4%, 1.3%, 48.8% and 31.3% of strains, respectively. Overall, E. faecium and E. faecalis were most frequently associated with hospital-acquired enterococcal infections in Zhejiang Province. All aminoglycoside resistance genes, except aph(2''-Id, were significantly more prevalent in HLAR strains than amongst high level aminoglycoside susceptible (HLAS strains, while there was no significant difference between HLAR and HLAS strains in regard to the prevalence of virulence genes, apart from esp, therefore, measures should be taken to manage infections caused by multi-drug resistant Enterococcus species.

  8. Characterization of Aminoglycoside Resistance and Virulence Genes among Enterococcus spp. Isolated from a Hospital in China

    Science.gov (United States)

    Li, Wanxiang; Li, Jing; Wei, Quhao; Hu, Qingfeng; Lin, Xiaowei; Chen, Mengquan; Ye, Renji; Lv, Huoyang

    2015-01-01

    This study investigated the aminoglycoside resistance phenotypes and genotypes, as well as the prevalence of virulence genes, in Enterococcus species isolated from clinical patients in China. A total of 160 enterococcal isolates from various clinical samples collected from September 2013 to July 2014 were identified to the species level using the VITEK-2 COMPACT system. The antimicrobial susceptibilities of the identified Enterococcus strains were determined by the Kirby-Bauer (K-B) disc diffusion method. PCR-based assays were used to detect the aminoglycoside resistance and virulence genes in all enterococcal isolates. Of 160 Enterococcus isolates, 105 were identified as E. faecium, 35 as E. faecalis, and 20 isolates were classified as “other” Enterococcus species. High-level aminoglycoside resistance (HLAR) for gentamicin, streptomycin, and both antibiotics was identified in 58.8, 50, and 34.4% of strains, respectively. The most common virulence gene (50.6% of isolates) was efaA, followed by asa1 (28.8%). The most prevalent aminoglycoside resistance genes were aac(6')-Ie-aph(2''), aph(2')-Id, aph(3')-IIIa, and ant(6')-Ia, present in 49.4%, 1.3%, 48.8% and 31.3% of strains, respectively. Overall, E. faecium and E. faecalis were most frequently associated with hospital-acquired enterococcal infections in Zhejiang Province. All aminoglycoside resistance genes, except aph(2'')-Id, were significantly more prevalent in HLAR strains than amongst high level aminoglycoside susceptible (HLAS) strains, while there was no significant difference between HLAR and HLAS strains in regard to the prevalence of virulence genes, apart from esp, therefore, measures should be taken to manage infections caused by multi-drug resistant Enterococcus species. PMID:25768240

  9. Fitness cost and interference of Arm/Rmt aminoglycoside resistance with the RsmF housekeeping methyltransferases.

    Science.gov (United States)

    Gutierrez, Belen; Escudero, Jose A; San Millan, Alvaro; Hidalgo, Laura; Carrilero, Laura; Ovejero, Cristina M; Santos-Lopez, Alfonso; Thomas-Lopez, Daniel; Gonzalez-Zorn, Bruno

    2012-05-01

    Arm/Rmt methyltransferases have emerged recently in pathogenic bacteria as enzymes that confer high-level resistance to 4,6-disubstituted aminoglycosides through methylation of the G1405 residue in the 16S rRNA (like ArmA and RmtA to -E). In prokaryotes, nucleotide methylations are the most common type of rRNA modification, and they are introduced posttranscriptionally by a variety of site-specific housekeeping enzymes to optimize ribosomal function. Here we show that while the aminoglycoside resistance methyltransferase RmtC methylates G1405, it impedes methylation of the housekeeping methyltransferase RsmF at position C1407, a nucleotide that, like G1405, forms part of the aminoglycoside binding pocket of the 16S rRNA. To understand the origin and consequences of this phenomenon, we constructed a series of in-frame knockout and knock-in mutants of Escherichia coli, corresponding to the genotypes rsmF(+), ΔrsmF, rsmF(+) rmtC(+), and ΔrsmF rmtC(+). When analyzed for the antimicrobial resistance pattern, the ΔrsmF bacteria had a decreased susceptibility to aminoglycosides, including 4,6- and 4,5-deoxystreptamine aminoglycosides, showing that the housekeeping methylation at C1407 is involved in intrinsic aminoglycoside susceptibility in E. coli. Competition experiments between the isogenic E. coli strains showed that, contrary to expectation, acquisition of rmtC does not entail a fitness cost for the bacterium. Finally, matrix-assisted laser desorption ionization (MALDI) mass spectrometry allowed us to determine that RmtC methylates the G1405 residue not only in presence but also in the absence of aminoglycoside antibiotics. Thus, the coupling between housekeeping and acquired methyltransferases subverts the methylation architecture of the 16S rRNA but elicits Arm/Rmt methyltransferases to be selected and retained, posing an important threat to the usefulness of aminoglycosides worldwide.

  10. Application of Continuous Culture for Assessing Antibiotic Activity Against Mycobacterium tuberculosis.

    Science.gov (United States)

    Hendon-Dunn, Charlotte L; Anwar, Saba; Burton, Christopher; Bacon, Joanna

    2018-01-01

    There is a proportion of the M. tuberculosis population that is refractory to the bactericidal action of antituberculosis antibiotics due to phenotypic tolerance. This tolerance can be impacted by environmental stimuli and the subsequent physiological state of the organism. It may be the result of preexisting populations of slow growing/non replicating bacteria that are protected from antibiotic action. It still remains unclear how the slow growth of M. tuberculosis contributes to antibiotic resistance and antibiotic tolerance. Here, we present a method for assessing the activity of antibiotics against M. tuberculosis using continuous culture, which is the only system that can be used to control bacterial growth rate and study the impact of slow or fast growth on the organism's response to antibiotic exposure.

  11. The Impact of Aminoglycosides on the Dynamics of Translation Elongation

    Directory of Open Access Journals (Sweden)

    Albert Tsai

    2013-02-01

    Full Text Available Inferring antibiotic mechanisms on translation through static structures has been challenging, as biological systems are highly dynamic. Dynamic single-molecule methods are also limited to few simultaneously measurable parameters. We have circumvented these limitations with a multifaceted approach to investigate three structurally distinct aminoglycosides that bind to the aminoacyl-transfer RNA site (A site in the prokaryotic 30S ribosomal subunit: apramycin, paromomycin, and gentamicin. Using several single-molecule fluorescence measurements combined with structural and biochemical techniques, we observed distinct changes to translational dynamics for each aminoglycoside. While all three drugs effectively inhibit translation elongation, their actions are structurally and mechanistically distinct. Apramycin does not displace A1492 and A1493 at the decoding center, as demonstrated by a solution nuclear magnetic resonance structure, causing only limited miscoding; instead, it primarily blocks translocation. Paromomycin and gentamicin, which displace A1492 and A1493, cause significant miscoding, block intersubunit rotation, and inhibit translocation. Our results show the power of combined dynamics, structural, and biochemical approaches to elucidate the complex mechanisms underlying translation and its inhibition.

  12. The impact of aminoglycosides on the dynamics of translation elongation

    Science.gov (United States)

    Tsai, Albert; Uemura, Sotaro; Johansson, Magnus; Puglisi, Elisabetta Viani; Marshall, R. Andrew; Aitken, Colin Echeverría; Korlach, Jonas; Ehrenberg, Måns; Puglisi, Joseph D.

    2013-01-01

    Inferring antibiotic mechanisms on translation through static structures has been challenging as biological systems are highly dynamic. Dynamic single-molecule methods are also limited to few simultaneously-measurable parameters. We have circumvented these limitations with a multifaceted approach to investigate three structurally-distinct aminoglycosides that bind to the aminoacyl-tRNA site (A site) in the prokaryotic 30S ribosomal subunit: apramycin, paromomycin, and gentamicin. Using several single-molecule fluorescence measurements combined with structural and biochemical techniques, we observed distinct changes to translational dynamics for each aminoglycoside. While all three drugs effectively inhibit translation elongation, their actions are structurally and mechanistically distinct. Apramycin does not displace A1492 and A1493 at the decoding center, as demonstrated by a solution NMR structure, causing only limited miscoding; instead it primarily blocks translocation. Paromomycin and gentamicin, which displace A1492 and A1493, cause significant miscoding, block intersubunit rotation, and inhibit translocation. Our results show the power of combined dynamics, structural, and biochemical approaches to elucidate the complex mechanisms underlying translation and its inhibition. PMID:23416053

  13. A new antibiotic with potent activity targets MscL.

    Science.gov (United States)

    Iscla, Irene; Wray, Robin; Blount, Paul; Larkins-Ford, Jonah; Conery, Annie L; Ausubel, Frederick M; Ramu, Soumya; Kavanagh, Angela; Huang, Johnny X; Blaskovich, Mark A; Cooper, Matthew A; Obregon-Henao, Andres; Orme, Ian; Tjandra, Edwin S; Stroeher, Uwe H; Brown, Melissa H; Macardle, Cindy; van Holst, Nick; Ling Tong, Chee; Slattery, Ashley D; Gibson, Christopher T; Raston, Colin L; Boulos, Ramiz A

    2015-07-01

    The growing problem of antibiotic-resistant bacteria is a major threat to human health. Paradoxically, new antibiotic discovery is declining, with most of the recently approved antibiotics corresponding to new uses for old antibiotics or structurally similar derivatives of known antibiotics. We used an in silico approach to design a new class of nontoxic antimicrobials for the bacteria-specific mechanosensitive ion channel of large conductance, MscL. One antimicrobial of this class, compound 10, is effective against methicillin-resistant Staphylococcus aureus with no cytotoxicity in human cell lines at the therapeutic concentrations. As predicted from in silico modeling, we show that the mechanism of action of compound 10 is at least partly dependent on interactions with MscL. Moreover we show that compound 10 cured a methicillin-resistant S. aureus infection in the model nematode Caenorhabditis elegans. Our work shows that compound 10, and other drugs that target MscL, are potentially important therapeutics against antibiotic-resistant bacterial infections.

  14. Multifunctional hyperbranched glycoconjugated polymers based on natural aminoglycosides.

    Science.gov (United States)

    Chen, Mingsheng; Hu, Mei; Wang, Dali; Wang, Guojian; Zhu, Xinyuan; Yan, Deyue; Sun, Jian

    2012-06-20

    Multifunctional gene vectors with high transfection, low cytotoxicity, and good antitumor and antibacterial activities were prepared from natural aminoglycosides. Through the Michael-addition polymerization of gentamycin and N,N'-methylenebisacrylamide, cationic hyperbranched glycoconjugated polymers were synthesized, and their physical and chemical properties were analyzed by FTIR, (1)H NMR, (13)C NMR, GPC, ζ-potential, and acid-base titration techniques. The cytotoxicity of these hyperbranched glycoconjugated polycations was low because of the hydrolysis of degradable glycosidic and amide linkages in acid conditions. Owing to the presence of various primary, secondary, and tertiary amines in the polymers, hyperbranched glycoconjugated polymers showed high buffering capacity and strong DNA condensation ability, resulting in the high transfection efficiency. In the meantime, due to the introduction of natural aminoglycosides into the polymeric backbone, the resultant hyperbranched glycoconjugated polymers inhibited the growth of cancer cells and bacteria efficiently. Combining the gene transfection, antitumor, and antibacterial abilities together, the multifunctional hyperbranched glycoconjugated polymers based on natural aminoglycosides may play an important role in protecting cancer patients from bacterial infections.

  15. Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients.

    Science.gov (United States)

    Islam, S; Oh, H; Jalal, S; Karpati, F; Ciofu, O; Høiby, N; Wretlind, B

    2009-01-01

    In total, 40 Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients were included in this study. Twenty of these were collected in 1994 and 1997, from six CF patients, and the rest were collected from different CF patients in 2000 and 2001. The relative expression of mRNA for the efflux pump protein MexY was determined by real-time PCR and correlated with susceptibilities to amikacin and tobramycin. The chromosomal genes mexZ, rplY, galU, PA5471 and nuoG, which were found to have a role in the gradual increase in MICs of aminoglycoside antibiotics in laboratory mutants of P. aeruginosa, were analysed. MexY mRNA overproduction was found in 17/20 isolates collected in 1994 and 1997, and was correlated with decreased susceptibility to aminoglycosides. Alteration of the MexXY-OprM efflux system has been the main mechanism of resistance to aminoglycoside antibiotics in CF P. aeruginosa isolates over the 3-year period. In several isolates, expression of the PA5471 gene product might have some effect on elevated MICs of aminoglycosides. Inactivation of rplY, galU and/or nuoG may explain the gradual increase in MICs of aminoglycosides in laboratory mutants but probably not in the CF environment, as rplY and galU were unaltered in all isolates, and nuoG was not expressed in only one isolate. No 16S rRNA A-site mutations were found in any of the four copies of the gene in 13 investigated isolates.

  16. Structural Studies of Bacterial Enzymes and their Relation to Antibiotic Resistance Mechanisms - Final Paper

    Energy Technology Data Exchange (ETDEWEB)

    Maltz, Lauren [SLAC National Accelerator Lab., Menlo Park, CA (United States)

    2015-08-27

    By using protein crystallography and X-ray diffraction, structures of bacterial enzymes were solved to gain a better understanding of how enzymatic modification acts as an antibacterial resistance mechanism. Aminoglycoside phosphotransferases (APHs) are one of three aminoglycoside modifying enzymes that confer resistance to the aminoglycoside antibiotics via enzymatic modification, rendering many drugs obsolete. Specifically, the APH(2”) family vary in their substrate specificities and also in their preference for the phosphate donor (ADP versus GDP). By solving the structures of members of the APH(2”) family of enzymes, we can see how domain movements are important to their substrate specificity. Our structure of the ternary complex of APH(2”)-IIIa with GDP and kanamycin, when compared to the known structures of APH(2”)-IVa, reveals that there are real physical differences between these two enzymes, a structural finding that explains why the two enzymes differ in their preferences for certain aminoglycosides. Another important group of bacterial resistance enzymes are the Class D β- lactamases. Oxacillinase carbapenemases (OXAs) are part of this enzyme class and have begun to confer resistance to ‘last resort’ drugs, most notably carbapenems. Our structure of OXA-143 shows that the conformational flexibility of a conserved hydrophobic residue in the active site (Val130) serves to control the entry of a transient water molecule responsible for a key step in the enzyme’s mechanism. Our results provide insight into the structural mechanisms of these two different enzymes

  17. In vitro and in vivo activities of antibiotic PM181104

    Digital Repository Service at National Institute of Oceanography (India)

    Mahajan, G.B.; Thomas, B.; Parab, R.; Patel, Z.E.; Kuldharan, S.; Yemparala, V.; Mishra, P.D.; Ranadive, P.; DeSouza, L.; Pari, K.; Sivaramkrishnan, H.

    -interval starting from 2 hours post dosing up to 24 hours post dosing. The thighs were removed at each time point and processed for cfu determination. Efficacy of PM181104 against MRSA in murine lung infection model Female Balb/c mice, weighing between 18 and 21... to the control group. 25mg/kg standard antibiotic linezolid by i.p. route and 110mg/kg standard antibiotic vancomycin by i.v. route was administered to the two positive control groups. Mice were euthanized 48 hours post-infection and their lungs collected...

  18. Rapid determination of bacterial aminoglycoside resistance in environmental samples using membrane electrospray ionization mass spectrometry.

    Science.gov (United States)

    Fan, Liusheng; Ke, Ming; Yuan, Min; Pu, Ji; Li, Juan; Lu, Jinxing; Xu, Jianguo; Zhang, Mei; Xu, Wei

    2016-08-01

    Antibiotic resistance in pathogenic bacteria is becoming a global public health problem, such as aminoglycoside resistance encoded by the armA gene. Although many methods have been reported, rapid analysis of environmental samples is still challenging. A rapid analytical method was developed in this study to determine bacterial aminoglycoside resistance using membrane electrospray ionization mass spectrometry (MESI-MS). Precursor/product-ion pairs of ArmA unique peptides were detected with minimal sample preparation. Standard peptides were synthesized and used for developing and validating the methodology, and then the method was verified by both ArmA positive and ArmA negative simulated environmental samples. A rapid method for determination of bacterial aminoglycoside resistance was developed using MESI-MS/MS. The bacterial cultural time was optimized to 2 hours, and the precision, accuracy and recovery of this method were investigated. The peptide IHSSTNER (IR-8) unique to ArmA in simulated environmental samples can be successfully identified within 3 hours. The novel assay offered a rapid method to determine bacterial aminoglycoside resistance with high sensitivity, accuracy and precision in simulated environmental samples. This method could also be applied to identify other drug-resistance proteins in clinical/environmental samples. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  19. Extracellular DNA Shields against Aminoglycosides in Pseudomonas aeruginosa Biofilms

    DEFF Research Database (Denmark)

    Chiang, Wen-Chi; Nilsson, Martin; Jensen, Peter Østrup

    2013-01-01

    provide evidence that extracellular DNA shields against aminoglycosides in Pseudomonas aeruginosa biofilms. We show that exogenously supplemented DNA integrates into P. aeruginosa biofilms and increases their tolerance toward aminoglycosides. We provide evidence that biofilms formed by a DNA release...

  20. Covalently linked kanamycin - Ciprofloxacin hybrid antibiotics as a tool to fight bacterial resistance.

    Science.gov (United States)

    Shavit, Michal; Pokrovskaya, Varvara; Belakhov, Valery; Baasov, Timor

    2017-06-01

    To address the growing problem of antibiotic resistance, a set of 12 hybrid compounds that covalently link fluoroquinolone (ciprofloxacin) and aminoglycoside (kanamycin A) antibiotics were synthesized, and their activity was determined against both Gram-negative and Gram-positive bacteria, including resistant strains. The hybrids were antagonistic relative to the ciprofloxacin, but were substantially more potent than the parent kanamycin against Gram-negative bacteria, and overcame most dominant resistance mechanisms to aminoglycosides. Selected hybrids were 42-640 fold poorer inhibitors of bacterial protein synthesis than the parent kanamycin, while they displayed similar inhibitory activity to that of ciprofloxacin against DNA gyrase and topoisomerase IV enzymes. The hybrids showed significant delay of resistance development in both E. coli and B. subtilis in comparison to that of component drugs alone or their 1:1 mixture. More generally, the data suggest that an antagonistic combination of aminoglycoside-fluoroquinolone hybrids can lead to new compounds that slowdown/prevent the emergence of resistance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Elimination of Substances with Antibiotic or Estrogenic Activity from Dewatered Sewage Sludge.

    OpenAIRE

    Innemanová, P.

    2017-01-01

    In our study, we focused on substances with inhibitory (antibiotic) and estrogenic (endocrine disruptors) activity to assess the unpredictable risk to the soil environment associated with the usage of sewage sludge as a fertilizer in agriculture.

  2. On Vitro Activity Of Pefloxacin And Other Antibiotics Against Grm ...

    African Journals Online (AJOL)

    Gram negative organisms have continued to generate much interest in bacterial infections in the university College Hospital, Ibadan (UCH), because most of them are multiple drug resistant, and are resistant to many antibiotics available. The present study confirms an increasing percentage of common isolate resistant to ...

  3. Local mechanisms for loud sound-enhanced aminoglycoside entry into outer hair cells.

    Science.gov (United States)

    Li, Hongzhe; Kachelmeier, Allan; Furness, David N; Steyger, Peter S

    2015-01-01

    Loud sound exposure exacerbates aminoglycoside ototoxicity, increasing the risk of permanent hearing loss and degrading the quality of life in affected individuals. We previously reported that loud sound exposure induces temporary threshold shifts (TTS) and enhances uptake of aminoglycosides, like gentamicin, by cochlear outer hair cells (OHCs). Here, we explore mechanisms by which loud sound exposure and TTS could increase aminoglycoside uptake by OHCs that may underlie this form of ototoxic synergy. Mice were exposed to loud sound levels to induce TTS, and received fluorescently-tagged gentamicin (GTTR) for 30 min prior to fixation. The degree of TTS was assessed by comparing auditory brainstem responses (ABRs) before and after loud sound exposure. The number of tip links, which gate the GTTR-permeant mechanoelectrical transducer (MET) channels, was determined in OHC bundles, with or without exposure to loud sound, using scanning electron microscopy. We found wide-band noise (WBN) levels that induce TTS also enhance OHC uptake of GTTR compared to OHCs in control cochleae. In cochlear regions with TTS, the increase in OHC uptake of GTTR was significantly greater than in adjacent pillar cells. In control mice, we identified stereociliary tip links at ~50% of potential positions in OHC bundles. However, the number of OHC tip links was significantly reduced in mice that received WBN at levels capable of inducing TTS. These data suggest that GTTR uptake by OHCs during TTS occurs by increased permeation of surviving, mechanically-gated MET channels, and/or non-MET aminoglycoside-permeant channels activated following loud sound exposure. Loss of tip links would hyperpolarize hair cells and potentially increase drug uptake via aminoglycoside-permeant channels expressed by hair cells. The effect of TTS on aminoglycoside-permeant channel kinetics will shed new light on the mechanisms of loud sound-enhanced aminoglycoside uptake, and consequently on ototoxic synergy.

  4. Local Mechanisms for Loud Sound-Enhanced Aminoglycoside Entry into Outer Hair Cells

    Directory of Open Access Journals (Sweden)

    Hongzhe eLi

    2015-04-01

    Full Text Available Loud sound exposure exacerbates aminoglycoside ototoxicity, increasing the risk of permanent hearing loss and degrading the quality of life in affected individuals. We previously reported that loud sound exposure induces temporary threshold shifts (TTS and enhances uptake of aminoglycosides, like gentamicin, by cochlear outer hair cells (OHCs. Here, we explore mechanisms by which loud sound exposure and TTS could increase aminoglycoside uptake by OHCs that may underlie this form of ototoxic synergy.Mice were exposed to loud sound levels to induce TTS, and received fluorescently-tagged gentamicin (GTTR for 30 minutes prior to fixation. The degree of TTS was assessed by comparing auditory brainstem responses before and after loud sound exposure. The number of tip links, which gate the GTTR-permeant mechanoelectrical transducer (MET channels, was determined in OHC bundles, with or without exposure to loud sound, using scanning electron microscopy.We found wide-band noise (WBN levels that induce TTS also enhance OHC uptake of GTTR compared to OHCs in control cochleae. In cochlear regions with TTS, the increase in OHC uptake of GTTR was significantly greater than in adjacent pillar cells. In control mice, we identified stereociliary tip links at ~50% of potential positions in OHC bundles. However, the number of OHC tip links was significantly reduced in mice that received WBN at levels capable of inducing TTS.These data suggest that GTTR uptake by OHCs during TTS occurs by increased permeation of surviving, mechanically-gated MET channels, and/or non-MET aminoglycoside-permeant channels activated following loud sound exposure. Loss of tip links would hyperpolarize hair cells and potentially increase drug uptake via aminoglycoside-permeant channels expressed by hair cells. The effect of TTS on aminoglycoside-permeant channel kinetics will shed new light on the mechanisms of loud sound-enhanced aminoglycoside uptake, and consequently on ototoxic

  5. Carbohydrate-Based Host-Guest Complexation of Hydrophobic Antibiotics for the Enhancement of Antibacterial Activity.

    Science.gov (United States)

    Jeong, Daham; Joo, Sang-Woo; Shinde, Vijay Vilas; Cho, Eunae; Jung, Seunho

    2017-08-08

    Host-guest complexation with various hydrophobic drugs has been used to enhance the solubility, permeability, and stability of guest drugs. Physical changes in hydrophobic drugs by complexation have been related to corresponding increases in the bioavailability of these drugs. Carbohydrates, including various derivatives of cyclodextrins, cyclosophoraoses, and some linear oligosaccharides, are generally used as host complexation agents in drug delivery systems. Many antibiotics with low bioavailability have some limitations to their clinical use due to their intrinsically poor aqueous solubility. Bioavailability enhancement is therefore an important step to achieve the desired concentration of antibiotics in the treatment of bacterial infections. Antibiotics encapsulated in a complexation-based drug delivery system will display improved antibacterial activity making it possible to reduce dosages and overcome the serious global problem of antibiotic resistance. Here, we review the present research trends in carbohydrate-based host-guest complexation of various hydrophobic antibiotics as an efficient delivery system to improve solubility, permeability, stability, and controlled release.

  6. Indirect resistance to several classes of antibiotics in cocultures with resistant bacteria expressing antibiotic-modifying or -degrading enzymes.

    Science.gov (United States)

    Nicoloff, Hervé; Andersson, Dan I

    2016-01-01

    Indirect resistance (IR), the ability of an antibiotic-resistant population of bacteria to protect a susceptible population, has been previously observed for β-lactamase-producing bacteria and associated with antimicrobial treatment failures. Here, we determined whether other resistance determinants could cause IR in the presence of five other classes of antibiotics. A test was designed to detect IR and 14 antibiotic resistance genes were tested in the presence of 13 antibiotics from six classes. A bioassay was used to measure the ability of resistance-causing enzymes to decrease the concentration of active antibiotics in the medium. We confirmed IR in the presence of β-lactam antibiotics (ampicillin and mecillinam) when TEM-1A was expressed. We found that bacteria expressing antibiotic-modifying or -degrading enzymes Ere(A), Tet(X2) or CatA1 caused IR in the presence of macrolides (erythromycin and clarithromycin), tetracyclines (tetracycline and tigecycline) and chloramphenicol, respectively. IR was not observed with resistance determinants that did not modify or destroy antibiotics or with enzymes modifying aminoglycosides or degrading fosfomycin. IR was dependent on the resistance enzymes decreasing the concentration of active antibiotics in the medium, hence allowing nearby susceptible bacteria to resume growth once the antibiotic concentration fell below their MIC. IR was not limited to β-lactamase-producing bacteria, but was also caused by resistant bacteria carrying cytoplasmic antibiotic-modifying or -degrading enzymes that catalyse energy-consuming reactions requiring complex cellular cofactors. Our results suggest that IR is common and further emphasizes that coinfecting agents and the human microflora can have a negative impact during antimicrobial therapy. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Synergistic antimicrobial activity between pentacyclic triterpenoids and antibiotics against Staphylococcus aureus strains

    Directory of Open Access Journals (Sweden)

    Navaratnam Parasakthi

    2011-06-01

    Full Text Available Abstract Background There has been considerable effort to discover plant-derived antibacterials against methicillin-resistant strains of Staphylococcus aureus (MRSA which have developed resistance to most existing antibiotics, including the last line of defence, vancomycin. Pentacyclic triterpenoid, a biologically diverse plant-derived natural product, has been reported to show anti-staphylococcal activities. The objective of this study is to evaluate the interaction between three pentacyclic triterpenoid and standard antibiotics (methicillin and vancomycin against reference strains of Staphylococcus aureus. Methods and Results The activity of the standard antibiotics and compounds on reference methicillin-sensitive and resistant strains of S. aureus were determined using the macrodilution broth method. The minimum inhibitory concentration (MIC of the compounds was compared with that of the standard antibiotics. The interaction between any two antimicrobial agents was estimated by calculating the fractional inhibitory concentration (FIC index of the combination. The various combinations of antibiotics and compounds reduced the MIC to a range of 0.05 to 50%. Conclusion Pentacyclic triterpenoids have shown anti-staphylococcal activities and although individually weaker than common antibiotics produced from bacteria and fungi, synergistically these compounds may use different mechanism of action or pathways to exert their antimicrobial effects, as implicated in the lowered MICs. Therefore, the use of current antibiotics could be maintained in their combination with plant-derived antibacterial agents as a therapeutic option in the treatment of S. aureus infections.

  8. Resistant gram-negative bacilli and antibiotic consumption in zarqa, jordan

    International Nuclear Information System (INIS)

    Bataineh, H.A.; Alrashed, K.M.

    2007-01-01

    To investigate the prevalence of antibiotic resistance among gram-negative bacteria in relation to antibiotic use in Prince Hashem Hospital (PHH), Jordan. One hundred consecutive gram-negative bacterial isolates from different sites were collected from patients admitted to the ICU at PHH. The susceptibilities of the strains to 12 antibiotics were performed and interpreted. The quantities and the numbers of the patients discharged on antibiotics and the quantities consumed were obtained from the hospital pharmacy records. The most common isolate was P. aeruginosa (n=21) The most common site of isolation was the respiratory tract (65%), The highest susceptibility was to piperacillin/ tazobactam(78%), and the lowest was to cefuroxime(34%). The aminoglycosides gentamicin and amikacin were active against 71% and 73% of the isolates respectively, Ciprofloxacin was active against 75% of the isolates. The most frequently used antibiotics were the third-generation cephalosporins ceftriaxone and ceftazidime, followed by imipenem and amikacin. Antibiotic resistance surveillance programs associated with registration of antibiotic consumption are necessary to promote optimal use of antibiotics. Rational prescribing of antibiotics should be encouraged through educational programs, surveillance and audit. Proper infection control measures should be practiced to prevent horizontal transfer of drug-resistant organisms. (author)

  9. Comprehensive study to investigate the role of various aminoglycoside resistance mechanisms in clinical isolates of Acinetobacter baumannii.

    Science.gov (United States)

    Sheikhalizadeh, Vajihe; Hasani, Alka; Ahangarzadeh Rezaee, Mohammad; Rahmati-Yamchi, Mohammad; Hasani, Akbar; Ghotaslou, Reza; Goli, Hamid Reza

    2017-02-01

    Therapeutic resistance towards most of the current treatment regime by Acinetobacter baumannii has reduced the prescribing antibiotic pattern and option is being re-shifted towards more toxic agents including aminoglycosides. The present investigation aimed at to study various mechanisms towards aminoglycoside non-susceptibility in clinical isolates of A. baumannii. The bacteria were subjected to genetic basis assessment for the presence of aminoglycoside modifying enzymes (AME), 16S rRNA methylase encoding genes and relative expression of AdeABC and AbeM efflux pumps in relation to their susceptibility to five aminoglycosides. When isolates were subjected to typing by repetitive extragenic palindromic (REP) PCR, isolates could be separated into thirteen definite clones. The majority of isolates (94%) were positive for AME encoding genes. Possession of ant(2')-Ia correlated with non-susceptibility towards gentamicin, amikacin, kanamycin, tobramycin; while, presence of aph(3')-VIa attributed to resistance towards amikacin, kanamycin; possession of aac(3')-Ia allied with non-susceptibility to amikacin, tobramycin and presence of aac(3')IIa correlated with kanamycin non-susceptibility. Presence of armA was detected in 34.4%, 34.2%, 29.2%, 40.3%, and 64.2% of isolates showing non-susceptibility to gentamicin, amikacin, kanamycin, tobramycin and netilmicin, respectively. No isolates were found to carry rmtB or rmtC. Amikacin non-susceptibility in comparison to other aminoglycosides correlated with over production of adeB. Overall, the results represented a definitive correlation between presence of AME encoding genes as well as armA and resistance of A. baumannii towards aminoglycosides. On the other hand, the up-regulation of AdeABC and AbeM systems was found to have only the partial role in development of aminoglycoside resistance. Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All

  10. Synergy between antibiotics and natural agents results in increased antimicrobial activity against Staphylococcus epidermidis.

    Science.gov (United States)

    Abidi, Syed Hani; Ahmed, Khalid; Sherwani, Sikander Khan; Kazmi, Shahana Urooj

    2015-09-27

    Staphylococcus epidermidis is one of the most frequent causes of biofilm-associated infections on indwelling medical devices. With the emergence of methicillin-resistant S. epidermidis (MRSE), there is an urgent need to discover novel active agents against a range of Gram-positive pathogens. We screened the clinical isolates of S. epidermidis for susceptibility/resistance against commonly prescribed antibiotics. Furthermore, we tested some natural agents alone and in combination with antibiotics to find possible synergistic antimicrobial effects. S. epidermidis clinical isolates were screened for susceptibility/resistance against vancomycin, erythromycin, tetracycline, chloramphenicol, ampicillin, ofloxacin, cephalexin, and gentamicin using the Kirby-Bauer disk diffusion method. The antimicrobial potential of Camellia sinensis, Juglans regia, and Hippophae rhamnoides alone and in combination with antibiotics were examined using the disk diffusion method, where the antimicrobial potential activity was measured in terms of formation of zones of inhibition. Most S. epidermidis isolates were found to be resistant to one or more antibiotics. Gentamycin and ofloxacin were found to be the most effective antibiotics against S. epidermidis isolates. Extracts of Hippophae rhamnoides, Juglans regia, and Camellia sinensis were found to be equally effective against S. epidermidis isolates. In combination with antibiotics, these extracts exhibited appreciable synergistic activity; the highest synergistic activity was observed with erythromycin and cephalexin. In the case of cephalexin, a reversion in resistance was observed. The plant extracts used in the study exhibited additive and synergistic antibacterial activity against S. epidermidis, hence providing an effective alternative to deal with the problem of multidrug resistance.

  11. Urinary antibiotic activity in paediatric patients attending an outpatient department in north-western Cambodia.

    Science.gov (United States)

    Emary, Katherine R W; Carter, Michael J; Pol, Sreymom; Sona, Soeng; Kumar, Varun; Day, Nicholas P J; Parry, Christopher M; Moore, Catrin E

    2015-01-01

    Antibiotic resistance is a prominent public and global health concern. We investigated antibiotic use in children by determining the proportion of unselected children with antibacterial activity in their urine attending a paediatric outpatient department in Siem Reap, Cambodia. Caregiver reports of medication history and presence of possible infection symptoms were collected in addition to urine samples. Urine antibiotic activity was estimated by exposing bacteria to urine specimens, including assessment against multiresistant bacteria previously isolated from patients in the hospital (a methicillin-resistant Staphylococcus aureus (MRSA), a multiresistant Salmonella typhi and an extended-spectrum β-lactamase (ESBL)-producing Escherichia coli isolate). Medication information and urine were collected from 775 children. Caregivers reported medication use in 69.0% of children in the preceding 48 h. 31.7% samples showed antibacterial activity; 16.3% showed activity against a local multiresistant organism. No specimens demonstrated activity against an ESBL-producing E. coli. Antibiotics are widely used in the community setting in Cambodia. Parents are often ill-informed about drugs given to treat their children. Increasing the regulation and training of private pharmacies in Cambodia may be necessary. Regional surveillance of antibiotic use and resistance is also essential in devising preventive strategies against further development of antibiotic resistance, which would have both local and global consequences. © 2014 The Authors. Tropical Medicine & International Health Published by John Wiley & Sons Ltd.

  12. Enhanced Antimicrobial Activity Of Antibiotics Mixed With Metal Nanoparticles

    Science.gov (United States)

    Kumar, Sandeep; Kumar, Neeraj; Bhanjana, Gaurav; Thakur, Rajesh; Dilbaghi, Neeraj

    2011-12-01

    Current producers of antimicrobial technology have a long lasting, environmentally safe, non-leaching, water soluble solution that will eventually replace all poisons and heavy metals. The transition metal ions inevitably exist as metal complexes in biological systems by interaction with the numerous molecules possessing groupings capable of complexation or chelation. Nanoparticles of metal oxides offer a wide variety of potential applications in medicine due to the unprecedented advances in nanobiotechnology research. the bacterial action of antibiotics like penicillin, erythryomycin, ampicillin, streptomycin, kanamycin etc. and that of a mixture of antibiotics and metal and metal oxide nanoparticles like zinc oxide, zirconium, silver and gold on microbes was examined by the agar-well-diffusion method, enumeration of colony-forming units (CFU) and turbidimetry.

  13. Anoxia inhibits biofilm development and modulates antibiotic activity.

    Science.gov (United States)

    Hess, Donavon J; Henry-Stanley, Michelle J; Lusczek, Elizabeth R; Beilman, Gregory J; Wells, Carol L

    2013-09-01

    Many infections involve bacterial biofilms that are notoriously antibiotic resistant. Unfortunately, the mechanism for this resistance is unclear. We tested the effect of oxygen concentration on development of Staphylococcus aureus biofilms, and on the ability of gentamicin and vancomycin to inhibit biofilm development. To mimic catheter-associated biofilms, silastic coupons were inoculated with 10(7)S aureus and incubated either aerobically (∼21% O2) or anaerobically (10% CO2, 5% H2, 85% N2) for 16 h at 37°C with varying concentrations of gentamicin and vancomycin. Viable colony-forming units were quantified from sonicated biofilms, and the crystal violet assay quantified biofilm biomass. Metabolomic profiles probed biochemical differences between aerobic and anaerobic biofilms. Control biofilms (no antibiotic) cultivated aerobically contained 8.1-8.6 log10S aureus. Anaerobiasis inhibited biofilm development, quantified by viable bacterial numbers and biomass (P vancomycin was more uniform aerobically and anaerobically, although at high bactericidal concentrations, vancomycin effectiveness was decreased under anoxia. There were notable differences in the metabolomic profiles of biofilms cultivated under normoxia versus anoxia. Compared with aerobic incubation, anaerobiasis resulted in decreased biofilm development, and metabolomics is a promising tool to identify key compounds involved in biofilm formation. The effectiveness of a specific antibiotic depended on its mode of action, as well as on the oxygen concentration in the environment. Copyright © 2013 Elsevier Inc. All rights reserved.

  14. Rapid Aminoglycoside NP Test for Rapid Detection of Multiple Aminoglycoside Resistance in Enterobacteriaceae.

    Science.gov (United States)

    Nordmann, Patrice; Jayol, Aurélie; Dobias, Jan; Poirel, Laurent

    2017-04-01

    The rapid aminoglycoside NP (Nordmann/Poirel) test was developed to rapidly identify multiple aminoglycoside (AG) resistance in Enterobacteriaceae It is based on the detection of the glucose metabolism related to enterobacterial growth in the presence of a defined concentration of amikacin plus gentamicin. Formation of acid metabolites was evidenced by a color change (orange to yellow) of the red phenol pH indicator. The rapid aminoglycoside NP test was evaluated by using bacterial colonies of 18 AG-resistant isolates producing 16S rRNA methylases, 20 AG-resistant isolates expressing AG-modifying enzymes (acetyl-, adenyl-, and phosphotransferases), and 10 isolates susceptible to AG. Its sensitivity and specificity were 100% and 97%, respectively, compared to the broth dilution method, which was taken as the gold standard for determining aminoglycoside resistance. The test is inexpensive, rapid (<2 h), and implementable worldwide. Copyright © 2017 American Society for Microbiology.

  15. Rise and dissemination of aminoglycoside resistance: the aac(6′)-Ib paradigm

    Science.gov (United States)

    Ramirez, María S.; Nikolaidis, Nikolas; Tolmasky, Marcelo E.

    2013-01-01

    Enzymatic modification is a prevalent mechanism by which bacteria defeat the action of antibiotics. Aminoglycosides are often inactivated by aminoglycoside modifying enzymes encoded by genes present in the chromosome, plasmids, and other genetic elements. The AAC(6′)-Ib (aminoglycoside 6′-N-acetyltransferase type Ib) is an enzyme of clinical importance found in a wide variety of gram-negative pathogens. The AAC(6′)-Ib enzyme is of interest not only because of his ubiquity but also because of other characteristics, it presents significant microheterogeneity at the N-termini and the aac(6′)-Ib gene is often present in integrons, transposons, plasmids, genomic islands, and other genetic structures. Excluding the highly heterogeneous N-termini, there are 45 non-identical AAC(6′)-Ib related entries in the NCBI database, 32 of which have identical name in spite of not having identical amino acid sequence. While some variants conserved similar properties, others show dramatic differences in specificity, including the case of AAC(6′)-Ib-cr that mediates acetylation of ciprofloxacin representing a rare case where a resistance enzyme acquires the ability to utilize an antibiotic of a different class as substrate. Efforts to utilize antisense technologies to turn off expression of the gene or to identify enzymatic inhibitors to induce phenotypic conversion to susceptibility are under way. PMID:23730301

  16. Rise and dissemination of aminoglycoside resistance: the aac(6')-Ib paradigm.

    Science.gov (United States)

    Ramirez, María S; Nikolaidis, Nikolas; Tolmasky, Marcelo E

    2013-01-01

    Enzymatic modification is a prevalent mechanism by which bacteria defeat the action of antibiotics. Aminoglycosides are often inactivated by aminoglycoside modifying enzymes encoded by genes present in the chromosome, plasmids, and other genetic elements. The AAC(6')-Ib (aminoglycoside 6'-N-acetyltransferase type Ib) is an enzyme of clinical importance found in a wide variety of gram-negative pathogens. The AAC(6')-Ib enzyme is of interest not only because of his ubiquity but also because of other characteristics, it presents significant microheterogeneity at the N-termini and the aac(6')-Ib gene is often present in integrons, transposons, plasmids, genomic islands, and other genetic structures. Excluding the highly heterogeneous N-termini, there are 45 non-identical AAC(6')-Ib related entries in the NCBI database, 32 of which have identical name in spite of not having identical amino acid sequence. While some variants conserved similar properties, others show dramatic differences in specificity, including the case of AAC(6')-Ib-cr that mediates acetylation of ciprofloxacin representing a rare case where a resistance enzyme acquires the ability to utilize an antibiotic of a different class as substrate. Efforts to utilize antisense technologies to turn off expression of the gene or to identify enzymatic inhibitors to induce phenotypic conversion to susceptibility are under way.

  17. Aminoglycosides resistance in clinical isolates of Staphylococcus aureus from a University Hospital in Bialystok, Poland.

    Directory of Open Access Journals (Sweden)

    Katarzyna Kaczyńska

    2008-06-01

    Full Text Available Staphylococcus aureus obtained from a University Hospital in Poland were characterized in relation to resistance to aminoglycoside antibiotics and the distribution of the genes encoding the most clinically relevant aminoglycoside modifying enzymes (AMEs. Of a total of 118 S. aureus, 45 (38.1% isolates were found to be resistant to at least one of the tested antibiotics. All aminoglycoside resistant isolates except one 44 (97.8% were resistant to kanamycin. The majority of strains 37 (82.2% and 32 (71.1% expressed resistance to neomycin and tobramycin, respectively. Eleven strains (24.4% were resistant to gentamicin or amikacin. All S. aureus strains were sensitive to netilmicin. The most prevalent resistance gene was aac(6'-Ie+aph(2' found in 13 (28.9% strains and 12 (26.7% isolates carried ant(4'-Ia gene, whilst aph(3'-IIIa gene was detected in only 7 (15.6% isolates. Additionally, the ant(6-Ia and str genes were detected in 14 (31.1% and 2 (4.4% strains, respectively. Ten (22.2% strains resistant to amikacin, tobramycin, kanamycin or neomycin did not harbor any of the above-noted genes.

  18. Effects of salicylates and aminoglycosides on spontaneous otoacoustic emissions in the Tokay gecko.

    Science.gov (United States)

    Stewart, C E; Hudspeth, A J

    2000-01-04

    The high sensitivity and sharp frequency discrimination of hearing depend on mechanical amplification in the cochlea. To explore the basis of this active process, we examined the pharmacological sensitivity of spontaneous otoacoustic emissions (SOAEs) in a lizard, the Tokay gecko. In a quiet environment, each ear produced a complex but stable pattern of emissions. These SOAEs were reversibly modulated by drugs that affect mammalian otoacoustic emissions, the salicylates and the aminoglycoside antibiotics. The effect of a single i.p. injection of sodium salicylate depended on the initial power of the emissions: ears with strong control SOAEs displayed suppression at all frequencies, whereas those with weak control emissions showed enhancement. Repeated oral administration of acetylsalicylic acid reduced all emissions. Single i.p. doses of gentamicin or kanamycin suppressed SOAEs below 2.6 kHz, while modulating those above 2.6 kHz in either of two ways. For ears whose emission power at 2.6-5.2 kHz encompassed more than half of the total, individual emissions displayed facilitation as great as 35-fold. For the remaining ears, emissions dropped to as little as one-sixth of their initial values. The similarity of the responses of reptilian and mammalian cochleas to pharmacological intervention provides further evidence for a common mechanism of cochlear amplification.

  19. Occurrence and distribution of antibiotics in coastal water of the Bohai Bay, China: Impacts of river discharge and aquaculture activities

    International Nuclear Information System (INIS)

    Zou Shichun; Xu Weihai; Zhang Ruijie; Tang Jianhui; Chen Yingjun; Zhang Gan

    2011-01-01

    The presence of 21 antibiotics in six different groups was investigated in coastal water of the Bohai Bay. Meantime, to illuminate the potential effects caused by the river discharge and aquaculture activities, wastewater from three breeding plants and surface water from six rivers flowing into the Bohai Bay were also analyzed for the selected antibiotics. The result revealed that measured antibiotics in the North Bobai Bay were generally higher than those in the South, highlighting the remarkable effects of high density of human activities on the exposure of antibiotics in environment. The antibiotics found in the six rivers were generally higher than those in the Bohai Bay reflecting the important antibiotics source of river discharge. This study reveals that the high consumption of some antibiotics in aquaculture activities may pose high ecological risk to the bay. - Highlights: → Some antibiotics were ubiquitous with high concentration in the Bohai bay, North China. → The antibiotics were mainly from the six rivers discharge around the Bay. → Antibiotics are commonly used in aquaculture activities around the Bay. → Aquaculture was suggested to be an important antibiotics source in the Bay. - River discharge and aquaculture were suggested to be important sources for antibiotics occurred in the coastal water of the Bohai Bay, North China.

  20. A Simple Assay to Screen Antimicrobial Compounds Potentiating the Activity of Current Antibiotics

    Directory of Open Access Journals (Sweden)

    Junaid Iqbal

    2013-01-01

    Full Text Available Antibiotic resistance continues to pose a significant problem in the management of bacterial infections, despite advances in antimicrobial chemotherapy and supportive care. Here, we suggest a simple, inexpensive, and easy-to-perform assay to screen antimicrobial compounds from natural products or synthetic chemical libraries for their potential to work in tandem with the available antibiotics against multiple drug-resistant bacteria. The aqueous extract of Juglans regia tree bark was tested against representative multiple drug-resistant bacteria in the aforementioned assay to determine whether it potentiates the activity of selected antibiotics. The aqueous extract of J. regia bark was added to Mueller-Hinton agar, followed by a lawn of multiple drug-resistant bacteria, Salmonella typhi or enteropathogenic E. coli. Next, filter paper discs impregnated with different classes of antibiotics were placed on the agar surface. Bacteria incubated with extract or antibiotics alone were used as controls. The results showed a significant increase (>30% in the zone of inhibition around the aztreonam, cefuroxime, and ampicillin discs compared with bacteria incubated with the antibiotics/extract alone. In conclusion, our assay is able to detect either synergistic or additive action of J. regia extract against multiple drug-resistant bacteria when tested with a range of antibiotics.

  1. Heterologous Expression of Chaperones from Hyperthermophilic Archaea Inhibits Aminoglycoside-Induced Protein Misfolding in Escherichia coli.

    Science.gov (United States)

    Peng, S; Chu, Z; Lu, J; Li, D; Wang, Y; Yang, S; Zhang, Y

    2017-10-01

    Aminoglycoside antibiotics affect protein translation fidelity and lead to protein aggregation and an increase in intracellular oxidative stress level as well. The overexpression of the chaperonin GroEL/GroES system promotes short-term tolerance to aminoglycosides in Escherichia coli. Here, we demonstrated that the coexpression of prefoldin or Hsp60 originating from the hyperthermophilic archaeon Pyrococcus furiosus in E. coli cells can rescue cell growth and inhibit protein aggregation induced by streptomycin exposure. The results of our study show that hyperthermophilic chaperones endow E. coli with a higher tolerance to streptomycin than the GroEL/GroES system, and that they exert better effects on the reduction of intracellular protein misfolding, indicating that these chaperones have unique features and functions.

  2. Chromosomal mechanisms of aminoglycoside resistance in Pseudomonas aeruginosa isolates from cystic fibrosis patients

    DEFF Research Database (Denmark)

    Islam, S; Oh, H; Jalal, S

    2009-01-01

    In total, 40 Pseudomonas aeruginosa isolates from cystic fibrosis (CF) patients were included in this study. Twenty of these were collected in 1994 and 1997, from six CF patients, and the rest were collected from different CF patients in 2000 and 2001. The relative expression of mRNA for the efflux....... aeruginosa, were analysed. MexY mRNA overproduction was found in 17/20 isolates collected in 1994 and 1997, and was correlated with decreased susceptibility to aminoglycosides. Alteration of the MexXY-OprM efflux system has been the main mechanism of resistance to aminoglycoside antibiotics in CF P...... not in the CF environment, as rplY and galU were unaltered in all isolates, and nuoG was not expressed in only one isolate. No 16S rRNA A-site mutations were found in any of the four copies of the gene in 13 investigated isolates....

  3. Membrane-active macromolecules resensitize NDM-1 gram-negative clinical isolates to tetracycline antibiotics.

    Directory of Open Access Journals (Sweden)

    Divakara S S M Uppu

    Full Text Available Gram-negative 'superbugs' such as New Delhi metallo-beta-lactamase-1 (blaNDM-1 producing pathogens have become world's major public health threats. Development of molecular strategies that can rehabilitate the 'old antibiotics' and halt the antibiotic resistance is a promising approach to target them. We report membrane-active macromolecules (MAMs that restore the antibacterial efficacy (enhancement by >80-1250 fold of tetracycline antibiotics towards blaNDM-1 Klebsiella pneumonia and blaNDM-1 Escherichia coli clinical isolates. Organismic studies showed that bacteria had an increased and faster uptake of tetracycline in the presence of MAMs which is attributed to the mechanism of re-sensitization. Moreover, bacteria did not develop resistance to MAMs and MAMs stalled the development of bacterial resistance to tetracycline. MAMs displayed membrane-active properties such as dissipation of membrane potential and membrane-permeabilization that enabled higher uptake of tetracycline in bacteria. In-vivo toxicity studies displayed good safety profiles and preliminary in-vivo antibacterial efficacy studies showed that mice treated with MAMs in combination with antibiotics had significantly decreased bacterial burden compared to the untreated mice. This report of re-instating the efficacy of the antibiotics towards blaNDM-1 pathogens using membrane-active molecules advocates their potential for synergistic co-delivery of antibiotics to combat Gram-negative superbugs.

  4. Correction: Membrane-active macromolecules resensitize NDM-1 gram-negative clinical isolates to tetracycline antibiotics.

    Directory of Open Access Journals (Sweden)

    Divakara S S M Uppu

    Full Text Available Gram-negative 'superbugs' such as New Delhi metallo-beta-lactamase-1 (blaNDM-1 producing pathogens have become world's major public health threats. Development of molecular strategies that can rehabilitate the 'old antibiotics' and halt the antibiotic resistance is a promising approach to target them. We report membrane-active macromolecules (MAMsthat restore the antibacterial efficacy (enhancement by >80-1250 fold of tetracycline antibiotics towards blaNDM-1 Klebsiella pneumonia and blaNDM-1 Escherichia coli clinical isolates.Organismic studies showed that bacteria had an increased and faster uptake of tetracyclinein the presence of MAMs which is attributed to the mechanism of re-sensitization. Moreover,bacteria did not develop resistance to MAMs and MAMs stalled the development of bacterial resistance to tetracycline. MAMs displayed membrane-active properties such as dissipation of membrane potential and membrane-permeabilization that enabled higher uptake of tetracycline in bacteria. In-vivo toxicity studies displayed good safety profiles and preliminary in-vivo antibacterial efficacy studies showed that mice treated with MAMs in combination with antibiotics had significantly decreased bacterial burden compared to the untreated mice. This report of re-instating the efficacy of the antibiotics towards blaNDM-1 pathogens using membrane-active molecules advocates their potential for synergistic co-delivery of antibiotics to combat Gram-negative superbugs.

  5. [Resistance of Pseudomonas aeruginosa to antibiotics].

    Science.gov (United States)

    Wolska, Katarzyna; Kot, Barbara; Piechota, Małgorzata; Frankowska, Aneta

    2013-12-16

    The main problem in the treatment of nosocomial infections is the increasing drug resistance of microorganisms that cause them, limiting the number of effective antibiotics. Pseudomonas aeruginosa bacilli are the cause of many serious hospital-acquired infections occurring primarily in patients within high-risk groups. The most vulnerable are those with weakened immune systems, as well as those with extensive surgical wounds and burn wounds. Infections are usually of the nature of secondary infections, caused by multidrug strains. Due to the high antimicrobial activity, beta-lactams, aminoglycosides and quinolones are drugs commonly used in hospitals, both in prevention and treatment of infections with P. aeruginosa. However, their irrational use is associated with selection and spread of strains resistant to these antibiotics. Resistance of P. aeruginosa to antibiotics is the result of a number of independent co-occurring mechanisms. These are: reducing the membrane permeability, the efflux system, and production of enzymes inactivating and degrading antibiotics. The paper devotes special attention to the determination of resistance mechanisms responsible for this phenomenon.

  6. Does human activity impact the natural antibiotic resistance background? Abundance of antibiotic resistance genes in 21 Swiss lakes.

    Science.gov (United States)

    Czekalski, Nadine; Sigdel, Radhika; Birtel, Julia; Matthews, Blake; Bürgmann, Helmut

    2015-08-01

    Antibiotic resistance genes (ARGs) are emerging environmental contaminants, known to be continuously discharged into the aquatic environment via human and animal waste. Freshwater aquatic environments represent potential reservoirs for ARG and potentially allow sewage-derived ARG to persist and spread in the environment. This may create increased opportunities for an eventual contact with, and gene transfer to, human and animal pathogens via the food chain or drinking water. However, assessment of this risk requires a better understanding of the level and variability of the natural resistance background and the extent of the human impact. We have analyzed water samples from 21 Swiss lakes, taken at sampling points that were not under the direct influence of local contamination sources and analyzed the relative abundance of ARG using quantitative real-time PCR. Copy numbers of genes mediating resistance to three different broad-spectrum antibiotic classes (sulfonamides: sul1, sul2, tetracyclines: tet(B), tet(M), tet(W) and fluoroquinolones: qnrA) were normalized to copy numbers of bacterial 16S rRNA genes. We used multiple linear regression to assess if ARG abundance is related to human activities in the catchment, microbial community composition and the eutrophication status of the lakes. Sul genes were detected in all sampled lakes, whereas only four lakes contained quantifiable numbers of tet genes, and qnrA remained below detection in all lakes. Our data indicate higher abundance of sul1 in lakes with increasing number and capacity of wastewater treatment plants (WWTPs) in the catchment. sul2 abundance was rather related to long water residence times and eutrophication status. Our study demonstrates the potential of freshwater lakes to preserve antibiotic resistance genes, and provides a reference for ARG abundance from lake systems with low human impact as a baseline for assessing ARG contamination in lake water. Copyright © 2015 Elsevier Ltd. All rights

  7. rRNA chemical groups required for aminoglycoside binding.

    Science.gov (United States)

    Blanchard, S C; Fourmy, D; Eason, R G; Puglisi, J D

    1998-05-26

    Through an affinity chromatography based modification-interference assay, we have identified chemical groups within Escherichia coli 16S ribosomal RNA sequence that are required for binding the aminoglycoside antibiotic paromomycin. Paromomycin was covalently linked to solid support via a nine atom spacer from the 6"'-amine of ring IV, and chemical modifications to an A-site oligonucleotide that disrupted binding were identified. Positions in the RNA oligonucleotide that correspond to G1405(N7), G1491(N7), G1494(N7), A1408(N7), A1493(N7), A1408(N1), A1492(N1), and A1493(N1), as well as the pro-R phosphate oxygens of A1492 and A1493 in 16S rRNA are chemical groups that are essential for a high-affinity RNA-paromomycin interaction. These data are consistent with genetic, biochemical, and structural studies related to neomycin-class antibiotics and provide additional information for establishing an exact model for their interaction with the ribosome.

  8. Purification, crystallization and preliminary X-ray analysis of Enterococcus faecium aminoglycoside-2′′-phosphotransferase-Ib [APH(2′′)-Ib

    Energy Technology Data Exchange (ETDEWEB)

    Walanj, Rupa; Young, Paul; Baker, Heather M.; Baker, Edward N.; Metcalf, Peter [Laboratory of Structural Biology, School of Biological Sciences, University of Auckland, Auckland (New Zealand); Chow, Joseph W.; Lerner, Stephen [Division of Infectious Diseases, Wayne State University School of Medicine and VA Medical Center, Detroit, Michigan 48201 (United States); Vakulenko, Sergei [Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556 (United States); Smith, Clyde A., E-mail: csmith@slac.stanford.edu [Stanford Synchrotron Radiation Laboratory, Stanford University, Menlo Park, CA 94025 (United States); Laboratory of Structural Biology, School of Biological Sciences, University of Auckland, Auckland (New Zealand)

    2005-04-01

    APH(2′′)-Ib is an enzyme responsible for high-level gentamicin resistance in E. faecium isolates. Native crystals of this enzyme have been prepared and preliminary X-ray diffraction experiments have been undertaken. Bacterial resistance to the aminoglycoside antibiotics is primarily the result of deactivation of the drugs. Three families of enzymes are responsible for this activity, with one such family being the aminoglycoside phosphotransferases (APHs). The gene encoding one of these enzymes, APH(2′′)-Ib, has been cloned and the protein (comprising 299 amino-acid residues) expressed in Escherichia coli, purified and crystallized in the presence of 16%(w/v) PEG 3350 and gentamicin. The crystals belong to the monoclinic space group P2{sub 1}, with approximate unit-cell parameters a = 79.7, b = 58.8, c = 81.4 Å, β = 98.4°, and preliminary X-ray diffraction analysis is consistent with the presence of two molecules in the asymmetric unit. Synchrotron diffraction data to approximately 2.65 Å resolution were collected from a native APH(2′′)-Ib crystal at beamline BL9-2 at SSRL (Stanford, CA, USA). Selenium-substituted crystals have also been produced and structure determination is proceeding.

  9. Manipulation of pH Shift to Enhance the Growth and Antibiotic Activity of Xenorhabdus nematophila

    Directory of Open Access Journals (Sweden)

    Yonghong Wang

    2011-01-01

    Full Text Available To evaluate the effects of pH control strategy on cell growth and the production of antibiotic (cyclo(2-Me-BABA-Gly by Xenorhabdus nematophila and enhance the antibiotic activity. The effects of uncontrolled- (different initial pH and controlled-pH (different constant pH and pH-shift operations on cell growth and antibiotic activity of X. nematophila YL00I were examined. Experiments showed that the optimal initial pH for cell growth and antibiotic production of X. nematophila YL001 occurred at 7.0. Under different constant pH, a pH level of 7.5 was found to be optimal for biomass and antibiotic activity at 23.71 g/L and 100.0 U/mL, respectively. Based on the kinetic information relating to the different constant pH effects on the fermentation of X. nematophila YL001, a two-stage pH control strategy in which pH 6.5 was maintained for the first 24 h, and then switched to 7.5 after 24 h, was established to improve biomass production and antibiotic activity. By applying this pH-shift strategy, the maximal antibiotic activity and productivity were significantly improved and reaching 185.0 U/mL and 4.41 U/mL/h, respectively, compared to values obtained from constant pH operation (100.0 U/mL and 1.39 U/mL/h.

  10. Antibacterial activity of various antibiotics against oral streptococci isolated in the oral cavity.

    Science.gov (United States)

    Pasquantonio, G; Condò, S; Cerroni, L; Bikiqu, L; Nicoletti, M; Prenna, M; Ripa, S

    2012-01-01

    A total of 550 oral streptococci: 270 Streptococcus mitis, 110 Streptococcus sanguis, 90 Streptococcus anginosus, 50 Streptococcus mutans, 30 Streptococcus salivarius, were isolated from dental plaque and gengival crevices of patients and tested for their susceptibility to 12 β-lactam antibiotics and to 5 non-β-lactam antibiotics, using the microdiluition method. Overall, a reduced susceptibility to penicillin was recorded in 13.4% of cases. The percentage of strains resistant to penicillin appeared significantly higher in S. mitis (24%) than in S. sanguis (19%), in S. mutans (14%) and in S. salivarius (10%). No levels of penicillin resistance were shown by 90 strains of S. anginosus. In susceptibility test to antibiotics, imipenem was the most active molecule tested, confirming its general good activity against oral streptococci. Also third generation cephalosporins such as ceftriaxone and fourth generation cephalosporins such as cefepime, showed good activity. Chinolones, glycopeptides and rifampicin confirmed a good activity against oral streptococci.

  11. Occurrence and distribution of antibiotics in coastal water of the Bohai Bay, China: impacts of river discharge and aquaculture activities.

    Science.gov (United States)

    Zou, Shichun; Xu, Weihai; Zhang, Ruijie; Tang, Jianhui; Chen, Yingjun; Zhang, Gan

    2011-10-01

    The presence of 21 antibiotics in six different groups was investigated in coastal water of the Bohai Bay. Meantime, to illuminate the potential effects caused by the river discharge and aquaculture activities, wastewater from three breeding plants and surface water from six rivers flowing into the Bohai Bay were also analyzed for the selected antibiotics. The result revealed that measured antibiotics in the North Bobai Bay were generally higher than those in the South, highlighting the remarkable effects of high density of human activities on the exposure of antibiotics in environment. The antibiotics found in the six rivers were generally higher than those in the Bohai Bay reflecting the important antibiotics source of river discharge. This study reveals that the high consumption of some antibiotics in aquaculture activities may pose high ecological risk to the bay. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Medical-grade honey enriched with antimicrobial peptides has enhanced activity against antibiotic-resistant pathogens

    NARCIS (Netherlands)

    Kwakman, P. H. S.; de Boer, L.; Ruyter-Spira, C. P.; Creemers-Molenaar, T.; Helsper, J. P. F. G.; Vandenbroucke-Grauls, C. M. J. E.; Zaat, S. A. J.; te Velde, A. A.

    2011-01-01

    Honey has potent activity against both antibiotic-sensitive and -resistant bacteria, and is an interesting agent for topical antimicrobial application to wounds. As honey is diluted by wound exudate, rapid bactericidal activity up to high dilution is a prerequisite for its successful application. We

  13. Methanobactin: a copper binding compound having antibiotic and antioxidant activity isolated from methanotrophic bacteria

    Science.gov (United States)

    DiSpirito, Alan A [Ames, IA; Zahn, James A [Harbor Beach, MI; Graham, David W [Lawrence, KS; Kim, Hyung J [St. Paul, MN; Alterman, Michail [Lawrence, KS; Larive, Cynthia [Lawrence, KS

    2007-04-03

    A means and method for treating bacterial infection, providing antioxidant activity, and chelating copper using a copper binding compound produced by methanotrophic bacteria is described. The compound, known as methanobactin, is the first of a new class of antibiotics having gram-positive activity. Methanobactin has been sequenced, and its structural formula determined.

  14. Evolution of an Antibiotic Resistance Enzyme Constrained by Stability and Activity Trade-offs

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiaojun; Minasov, George; Shoichet, Brian K. (NWU)

    2010-03-08

    Pressured by antibiotic use, resistance enzymes have been evolving new activities. Does such evolution have a cost? To investigate this question at the molecular level, clinically isolated mutants of the {beta}-lactamase TEM-1 were studied. When purified, mutant enzymes had increased activity against cephalosporin antibiotics but lost both thermodynamic stability and kinetic activity against their ancestral targets, penicillins. The X-ray crystallographic structures of three mutant enzymes were determined. These structures suggest that activity gain and stability loss is related to an enlarged active site cavity in the mutant enzymes. In several clinically isolated mutant enzymes, a secondary substitution is observed far from the active site (Met182 {yields} Thr). This substitution had little effect on enzyme activity but restored stability lost by substitutions near the active site. This regained stability conferred an advantage in vivo. This pattern of stability loss and restoration may be common in the evolution of new enzyme activity.

  15. Disinfectant and antibiotic activities: a comparative analysis in Brazilian hospital bacterial isolates

    Directory of Open Access Journals (Sweden)

    Guimarães Márcia Aparecida

    2000-01-01

    Full Text Available Nosocomial infections are an important cause of morbidity and mortality all over the world. It has been shown that appropriate environmental hygienic and disinfection practices can be very helpful to hospital infection control. The purpose of this study was to evaluate the bactericidal activity of some disinfectants against antibiotic-susceptible and antibiotic-resistant hospital bacterial isolates. The susceptibility of 27 clinical isolates to disinfectants and antibiotics was determined by the Association of Official Analytical Chemist?s (AOAC Use-Dilution method and by the Kirby-Bauer method, respectively. All strains tested were susceptible to sodium hypochlorite, glutaraldehyde and to the association quaternary ammonium - formaldehyde - ethyl alcohol disinfectants. However, the susceptibility of strains to phenol and to one quaternary ammonium compound was variable. Among twenty-one antibiotic-multiresistant strains (methicillin-resistant staphylococci, Enterococcus spp, Pseudomonas aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae, Serratia marcescens and Escherichia coli eleven (52% and eight (38% strains were resistant to the quaternary ammonium and phenol compounds, respectively. Among six isolates that demonstrated susceptibility to antibiotics (staphylococci, Enterococcus spp, P. mirabilis, E. cloacae and E. coli two strains (33% showed resistance to these disinfectants. The results demonstrated the lack of correlation between antibiotic-susceptibility and susceptibility to disinfectants in hospital strains.

  16. Detection of antibiotic residues in poultry meat.

    Science.gov (United States)

    Sajid, Abdul; Kashif, Natasha; Kifayat, Nasira; Ahmad, Shabeer

    2016-09-01

    The antibiotic residues in poultry meat can pose certain hazards to human health among them are sensitivity to antibiotics, allergic reactions, mutation in cells, imbalance of intestinal micro biota and bacterial resistance to antibiotics. The purpose of the present paper was to detect antibiotic residue in poultry meat. During the present study a total of 80 poultry kidney and liver samples were collected and tested for detection of different antibiotic residues at different pH levels Eschericha coli at pH 6, 7 and Staphyloccocus aureus at pH 8 & 9. Out of 80 samples only 4 samples were positive for antibiotic residues. The highest concentrations of antibiotic residue found in these tissues were tetracycline (8%) followed by ampicilin (4%), streptomycine (2%) and aminoglycosides (1%) as compared to other antibiotics like sulfonamides, neomycine and gentamycine. It was concluded that these microorganism at these pH levels could be effectively used for detection of antibiotic residues in poultry meat.

  17. Effects of six selected antibiotics on plant growth and soil microbial and enzymatic activities

    Energy Technology Data Exchange (ETDEWEB)

    Liu Feng [State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, 511 Kehua Street, Tianhe District, Guangzhou 510640 (China); Ying Guangguo, E-mail: guangguo.ying@gmail.co [State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, 511 Kehua Street, Tianhe District, Guangzhou 510640 (China); Tao Ran; Zhao Jianliang; Yang Jifeng [State Key Laboratory of Organic Geochemistry, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, 511 Kehua Street, Tianhe District, Guangzhou 510640 (China); Zhao Lanfeng [College of Resource and Environmental Science, South China Agricultural University, Guangzhou 510642 (China)

    2009-05-15

    The potential impact of six antibiotics (chlortetracycline, tetracycline and tylosin; sulfamethoxazole, sulfamethazine and trimethoprim) on plant growth and soil quality was studied by using seed germination test on filter paper and plant growth test in soil, soil respiration and phosphatase activity tests. The phytotoxic effects varied between the antibiotics and between plant species (sweet oat, rice and cucumber). Rice was most sensitive to sulfamethoxazole with the EC10 value of 0.1 mg/L. The antibiotics tested inhibited soil phosphatase activity during the 22 days' incubation. Significant effects on soil respiration were found for the two sulfonamides (sulfamethoxazole and sulfamethazine) and trimethoprim, whereas little effects were observed for the two tetracyclines and tylosin. The effective concentrations (EC10 values) for soil respiration in the first 2 days were 7 mg/kg for sulfamethoxazole, 13 mg/kg for sulfamethazine and 20 mg/kg for trimethoprim. Antibiotic residues in manure and soils may affect soil microbial and enzyme activities. - Terrestrial ecotoxicological effects of antibiotics are related to their sorption and degradation behavior in soil.

  18. Effects of six selected antibiotics on plant growth and soil microbial and enzymatic activities

    International Nuclear Information System (INIS)

    Liu Feng; Ying Guangguo; Tao Ran; Zhao Jianliang; Yang Jifeng; Zhao Lanfeng

    2009-01-01

    The potential impact of six antibiotics (chlortetracycline, tetracycline and tylosin; sulfamethoxazole, sulfamethazine and trimethoprim) on plant growth and soil quality was studied by using seed germination test on filter paper and plant growth test in soil, soil respiration and phosphatase activity tests. The phytotoxic effects varied between the antibiotics and between plant species (sweet oat, rice and cucumber). Rice was most sensitive to sulfamethoxazole with the EC10 value of 0.1 mg/L. The antibiotics tested inhibited soil phosphatase activity during the 22 days' incubation. Significant effects on soil respiration were found for the two sulfonamides (sulfamethoxazole and sulfamethazine) and trimethoprim, whereas little effects were observed for the two tetracyclines and tylosin. The effective concentrations (EC10 values) for soil respiration in the first 2 days were 7 mg/kg for sulfamethoxazole, 13 mg/kg for sulfamethazine and 20 mg/kg for trimethoprim. Antibiotic residues in manure and soils may affect soil microbial and enzyme activities. - Terrestrial ecotoxicological effects of antibiotics are related to their sorption and degradation behavior in soil.

  19. Protein-inspired antibiotics active against vancomycin- and daptomycin-resistant bacteria.

    Science.gov (United States)

    Blaskovich, Mark A T; Hansford, Karl A; Gong, Yujing; Butler, Mark S; Muldoon, Craig; Huang, Johnny X; Ramu, Soumya; Silva, Alberto B; Cheng, Mu; Kavanagh, Angela M; Ziora, Zyta; Premraj, Rajaratnam; Lindahl, Fredrik; Bradford, Tanya A; Lee, June C; Karoli, Tomislav; Pelingon, Ruby; Edwards, David J; Amado, Maite; Elliott, Alysha G; Phetsang, Wanida; Daud, Noor Huda; Deecke, Johan E; Sidjabat, Hanna E; Ramaologa, Sefetogi; Zuegg, Johannes; Betley, Jason R; Beevers, Andrew P G; Smith, Richard A G; Roberts, Jason A; Paterson, David L; Cooper, Matthew A

    2018-01-02

    The public health threat posed by a looming 'post-antibiotic' era necessitates new approaches to antibiotic discovery. Drug development has typically avoided exploitation of membrane-binding properties, in contrast to nature's control of biological pathways via modulation of membrane-associated proteins and membrane lipid composition. Here, we describe the rejuvenation of the glycopeptide antibiotic vancomycin via selective targeting of bacterial membranes. Peptide libraries based on positively charged electrostatic effector sequences are ligated to N-terminal lipophilic membrane-insertive elements and then conjugated to vancomycin. These modified lipoglycopeptides, the 'vancapticins', possess enhanced membrane affinity and activity against methicillin-resistant Staphylococcus aureus (MRSA) and other Gram-positive bacteria, and retain activity against glycopeptide-resistant strains. Optimised antibiotics show in vivo efficacy in multiple models of bacterial infection. This membrane-targeting strategy has potential to 'revitalise' antibiotics that have lost effectiveness against recalcitrant bacteria, or enhance the activity of other intravenous-administered drugs that target membrane-associated receptors.

  20. Photo-activated porphyrin in combination with antibiotics: therapies against Staphylococci

    Science.gov (United States)

    Dastgheyb, Sana S.; Eckmann, David M.; Composto, Russell J.

    2013-01-01

    Staphylococcal infections have become difficult to treat due to antibiotic insensitivity and resistance. Antimicrobial combination therapies may minimize acquisition of resistance and photodynamic therapy is an attractive candidate for these combinations. In this manuscript, we explore combined use of antibiotics and meso-tetra (4-aminophenyl) porphine (TAPP), a cationic porphyrin, for treatment of Staphylococcus aureus contamination. We characterize the antimicrobial activity of photoactivated TAPP and show that activity is largely lost in the presence of a radical scavenger. Importantly, TAPP can be reactivated with continued, albeit attenuated, antibacterial activity. We then show that the antimicrobial activity of illuminated TAPP is additive with chloramphenicol and tobramycin for Staphylococcus aureus and Escherichia coli, and synergistic for MRSA and Staphylococcus epidermidis. Chloramphenicol + methylene blue, another photosensitizer, also show additivity against Staphylococcus aureus. In contrast, ceftriaxone and vancomycin do not strongly augment the low level effects of TAPP against S. aureus. Eukaryotic cells exhibit a dose-dependent toxicity with illuminated TAPP. Our results suggest that even sub-minimum inhibitory concentration levels of photo-activated TAPP could be used to boost the activity of waning antibiotics. This may play an important role in treatments reliant on antibiotic controlled release systems where augmentation with photo-active agents could extend their efficacy. PMID:24148969

  1. The relationship between the use of flucloxacillin, vancomycin, aminoglycosides and ciprofloxacin and the susceptibility patterns of coagulase-negative staphylococci recovered from blood cultures.

    NARCIS (Netherlands)

    Mulder, JG; Kosterink, JGW; Degener, JE

    1997-01-01

    Antibiotic use is a cause of selection of multiresistant bacterial strains. Over three years (1990-1992) we studied the relation between the use of flucloxacillin, vancomycin, aminoglycosides and ciprofloxacin and the susceptibility of coagulase-negative staphylococci (CNS) recovered from blood

  2. Antibiotic Resistance of Bacteria: A Global Challenge

    Indian Academy of Sciences (India)

    vealed several aminoglycoside resistances in nonculturable bac- teria. Notwithstanding the availability of so many antimicrobial agents, infectious diseases still remain the second leading cause of death worldwide. Eventually, the widespread occurrence of antibiotic-resistant bacteria has added a new dimension to the.

  3. Chronic otorrhoea: Spectrum of microorganisms and antibiotic ...

    African Journals Online (AJOL)

    Otorrhoea had a different microbial spectrum compared with international reports, with methicillin-resistant Staphylococcus aureus infection in a single patient. The organisms isolated were susceptible mainly to fluoroquinolones (96%) and aminoglycosides (81%). Conclusion. Amoxicillin is a poor choice of antibiotic due to ...

  4. Berberine is a novel type efflux inhibitor which attenuates the MexXY-mediated aminoglycoside resistance in Pseudomonas aeruginosa.

    Directory of Open Access Journals (Sweden)

    Yuji Morita

    2016-08-01

    Full Text Available The emergence and spread of multidrug-resistant P. aeruginosa infections is of great concern, as very few agents are effective against strains of this species. Methanolic extracts from the Coptidis Rhizoma (the rhizomes of Coptis japonica var. major Satake or Phellodendri Cortex (the bark of Phellodendron chinense Schneider markedly reduced resistance to anti-pseudomonal aminoglycosides (e.g. amikacin in multidrug-resistant P. aeruginosa strains. Berberine, the most abundant benzylisoquinoline alkaloid in the two extracts, reduced aminoglycoside resistance of P. aeruginosa via a mechanism that required the MexXY multidrug efflux system; berberine also reduced aminoglycoside MICs in Achromobacter xylosoxidans and Burkholderia cepacia, two species that harbor intrinsic multidrug efflux systems very similar to the MexXY. Furthermore this compound inhibited MexXY-dependent antibiotic resistance of other classes including cephalosporins (cefepime, macrolides (erythromycin, and lincosamides (lincomycin demonstrated using a pseudomonad lacking the 4 other major Mex pumps. Although phenylalanine-arginine beta-naphthylamide (PAβN, a well-known efflux inhibitor, antagonized aminoglycoside in a MexXY-dependent manner, a lower concentration of berberine was sufficient to reduce amikacin resistance of P. aeruginosa in the presence of PAβN. Moreover, berberine enhanced the synergistic effects of amikacin and piperacillin (and vice versa in multidrug-resistant P. aeruginosa strains. Thus, berberine appears to be a novel type inhibitor of the MexXY-dependent aminoglycoside efflux in P. aeruginosa. As aminoglycosides are molecules of choice to treat severe infections the clinical impact is potentially important.

  5. Antibiotics and Antibiotic Resistance

    Science.gov (United States)

    ... Drugs Resources for You Information for Consumers (Drugs) Buying & Using Medicine Safely Antibiotics and Antibiotic Resistance Antibiotics ... Antibiotic Resistance and Protect Public Health The White House Blog FDA’s Take on the Executive Order and ...

  6. Effects of oxytetracycline, tylosin, and amoxicillin antibiotics on specific methanogenic activity of anaerobic biomass

    Directory of Open Access Journals (Sweden)

    Mohammad Mehdi Amin

    2012-01-01

    Materials and Methods: To evaluate the inhibitory antibiotics amoxicillin, tetracycline, and tylosin on biomass activity, specific methanogenic activity (SMA using anerobic biomass batch; into 120 ml vials: 30 ml biomass and 70 ml substrate including volatile fatty acids, mainly acetic acid and various concentrations of antibiotics were added. Methane gas production replacement through solution of KOH (2 N as an absorber of CO 2 and bromine thymol blue as indicator was measured. Each batch was tested for 10 days. Results: Based on the findings, inhibitory concentration of oxytetracycline, amoxicillin, and tylosin were 8000, 9000, and 9000 mg/L, respectively. Conclusions: This study showed that with increasing concentrations of antibiotics, the produced biogas volume from biomass per unit weight is decreased. COD removal was 42-82 % due to long retention time and adsorption to flocks.

  7. Identification of Genes Coding Aminoglycoside Modifying Enzymes in E. coli of UTI Patients in India.

    Science.gov (United States)

    Mir, Abdul Rouf; Bashir, Yasir; Dar, Firdous Ahmad; Sekhar, M

    This study is to probe the pattern of antibiotic resistance against aminoglycosides and its mechanism in E. coli obtained from patients from Chennai, India. Isolation and identification of pathogens were done on MacConkey agar. Antimicrobial sensitivity testing was done by disc diffusion test. The identification of genes encoding aminoglycoside modifying enzymes was done by Polymerase Chain Reaction (PCR). Out of 98 isolates, 71 (72.45%) isolates were identified as E. coli and the remaining 27 (27.55%) as other bacteria. Disc diffusion method results showed a resistance level of 72.15% for streptomycin, 73.4% for gentamicin, 63.26% for neomycin, 57.14% for tobramycin, 47.9% for netilmicin, and 8.16% for amikacin in E. coli. PCR screening showed the presence of four genes, namely, rrs, aacC2, aacA-aphD, and aphA3, in their plasmid DNA. The results point towards the novel mechanism of drug resistance in E. coli from UTI patients in India as they confirm the presence of genes encoding enzymes that cause resistance to aminoglycoside drugs. This could be an alarm for drug prescription to UTI patients.

  8. Identification of Genes Coding Aminoglycoside Modifying Enzymes in E. coli of UTI Patients in India

    Directory of Open Access Journals (Sweden)

    Abdul Rouf Mir

    2016-01-01

    Full Text Available This study is to probe the pattern of antibiotic resistance against aminoglycosides and its mechanism in E. coli obtained from patients from Chennai, India. Isolation and identification of pathogens were done on MacConkey agar. Antimicrobial sensitivity testing was done by disc diffusion test. The identification of genes encoding aminoglycoside modifying enzymes was done by Polymerase Chain Reaction (PCR. Out of 98 isolates, 71 (72.45% isolates were identified as E. coli and the remaining 27 (27.55% as other bacteria. Disc diffusion method results showed a resistance level of 72.15% for streptomycin, 73.4% for gentamicin, 63.26% for neomycin, 57.14% for tobramycin, 47.9% for netilmicin, and 8.16% for amikacin in E. coli. PCR screening showed the presence of four genes, namely, rrs, aacC2, aacA-aphD, and aphA3, in their plasmid DNA. The results point towards the novel mechanism of drug resistance in E. coli from UTI patients in India as they confirm the presence of genes encoding enzymes that cause resistance to aminoglycoside drugs. This could be an alarm for drug prescription to UTI patients.

  9. Antibiotic susceptibility profile of Aeromonas spp. isolates from food in Abu Dhabi, United Arab Emirates.

    Science.gov (United States)

    Awan, Mohammad Bashir; Maqbool, Ahmed; Bari, Abdul; Krovacek, Karel

    2009-01-01

    A total of 57 Aeromonas isolates from food samples such as fresh and frozen chicken, game birds, pasteurized milk, baby food, bakery products, fruit and vegetables, fish, and water from Abu Dahbi, UAE were investigated for antibiotic susceptibility profile. Most strains were resistant to penicillins (ticarcillin, mezlocillin, oxacillin, piperacillin), sulfamethoxazole, trimethoprim and macrolides (erythromycin, vancomycin, clindamycin) but sensitive to tetracycline, chloramphenicol, nitrofurantoin, aminoglycosides (amikacin, gentamicin, tobramycin), cephalosporins (cefuroxime, ceftrioxone, cefazolin, cephalexin, cephalothin, cefoxitin, cefotaxime), quinolone (ciprofloxacin), colistin sulphate and SXT (trimethoprim-sulfamethoxazole). On the other hand, many antibiotics showed excellent inhibitory activity (>75% strains were sensitive to them) against all the strains tested. These include cefuroxime, ceftrioxone, ciprofloxacin, colistin, amikacin, gentamicin, tetracycline, chloramphenicol, nitrofurantoin, cefotaxime and tobramycin. In conclusion, the results show a detailed pattern of sensitivity of the various Aeromonas spp. isolates to a variety of antibiotics and provide useful information in the context of selective isolation and phenotypic identification of the aeromonads from food.

  10. Novel Aminoglycoside Resistance Transposons and Transposon-Derived Circular Forms Detected in Carbapenem-Resistant Acinetobacter baumannii Clinical Isolates

    Science.gov (United States)

    Dwibedi, Chinmay Kumar; Sjöström, Karin; Edquist, Petra; Wai, Sun Nyunt; Uhlin, Bernt Eric

    2016-01-01

    Acinetobacter baumannii has emerged as an important opportunistic pathogen equipped with a growing number of antibiotic resistance genes. Our study investigated the molecular epidemiology and antibiotic resistance features of 28 consecutive carbapenem-resistant clinical isolates of A. baumannii collected throughout Sweden in 2012 and 2013. The isolates mainly belonged to clonal complexes (CCs) with an extensive international distribution, such as CC2 (n = 16) and CC25 (n = 7). Resistance to carbapenems was related to blaOXA-23 (20 isolates), blaOXA-24/40-like (6 isolates), blaOXA-467 (1 isolate), and ISAba1-blaOXA-69 (1 isolate). Ceftazidime resistance was associated with blaPER-7 in the CC25 isolates. Two classical point mutations were responsible for resistance to quinolones in all the isolates. Isolates with high levels of resistance to aminoglycosides carried the 16S rRNA methylase armA gene. The isolates also carried a variety of genes encoding aminoglycoside-modifying enzymes. Several novel structures involved in aminoglycoside resistance were identified, including Tn6279, ΔTn6279, Ab-ST3-aadB, and different assemblies of Tn6020 and TnaphA6. Importantly, a number of circular forms related to the IS26 or ISAba125 composite transposons were detected. The frequent occurrence of these circular forms in the populations of several isolates indicates a potential role of these circular forms in the dissemination of antibiotic resistance genes. PMID:26824943

  11. Biotransformation of fluoroquinolone antibiotics by ligninolytic fungi - Metabolites, enzymes and residual antibacterial activity

    Czech Academy of Sciences Publication Activity Database

    Čvančarová, Monika; Moeder, M.; Filipová, Alena; Cajthaml, Tomáš

    2015-01-01

    Roč. 136, OCT 2015 (2015), s. 311-320 ISSN 0045-6535 R&D Projects: GA TA ČR TE01020218; GA ČR GA13-28283S Institutional support: RVO:61388971 Keywords : Fluoroquinolone antibiotics * White rot fungi * Residual antibacterial activity Subject RIV: EE - Microbiology, Virology Impact factor: 3.698, year: 2015

  12. Enhancement of the Norfloxacin Antibiotic Activity by Gaseous Contact with the Essential Oil of Croton zehntneri

    Science.gov (United States)

    Coutinho, HDM; Matias, EFF; Santos, KKA; Tintino, SR; Souza, CES; Guedes, GMM; Santos, FAD; Costa, JGM; Falcão-Silva, VS; Siqueira-Júnior, JP

    2010-01-01

    This is the first on the modulation of norfloxacin antibiotic activity by the volatile compounds of an essential oil. We report the chemical composition and antibiotic modifying activity of the essential oil extracted from the leaves of Croton zehntneri Pax et Hoffm (variety estragole), using the minimal inhibitory dose method and gaseous contact. The leaves of Croton zehntneri Pax et Hoffm (Euphorbiaceae) were subjected to hydrodistillation, and the essential oil extracted was examined with respect to the chemical composition, by gas chromatography-mass spectrometry (GC/MS), and to inhibitory activity of efflux pump by gaseous contact. The main component of the essential oil of C. zehntneri was estragole (76,8%). The gaseous components of the oil enhanced the inhibition zone of norfloxacin in 39,5%. This result shows that this oil influences the antibiotic activity of norfloxacin, possibly affecting the bacterial NorA efflux system, and may be used as an adjuvant in the antibiotic therapy of multidrug resistant pathogens. PMID:21264094

  13. Berberine Enhances the Antibacterial Activity of Selected Antibiotics against Coagulase-Negative Staphylococcus Strains in Vitro

    Directory of Open Access Journals (Sweden)

    Robert D. Wojtyczka

    2014-05-01

    Full Text Available Synergistic interactions between commonly used antibiotics and natural bioactive compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has proven efficacy against a broad spectrum of microorganisms. The aim of the presented work was to assess the antibacterial activity of berberine chloride in light of the effect exerted by common antibiotics on fourteen reference strains of Staphylococccus spp., and to evaluate the magnitude of interactions of berberine with these antistaphylococcal antibiotics. In our study minimum inhibitory concentrations (MIC of berberine chloride against CoNS ranged from 16 to 512 µg/mL. The most noticeable effects were observed for S. haemolyticus ATCC 29970, S. epidermidis ATCC 12228, S. capitis subsp. capitis ATCC 35661, S. galinarium ATCC 700401, S. hominis subsp. hominis ATCC 27844, S. intermedius ATCC 29663 and S. lugdunensis ATCC 49576. The most significant synergistic effect was noticed for berberine in combination with linezolid, cefoxitin and erythromycin. The synergy between berberine and antibiotics demonstrates the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections.

  14. Bioavailability of antibiotics at soil-water interfaces - A comparison of measured activities and equilibrium partitioning (EqP) estimates.

    Science.gov (United States)

    Menz, Jakob; Müller, Julia; Olsson, Oliver; Kümmerer, Klaus

    2018-04-09

    There are growing concerns that antibiotic pollution impacts environmental microbiota and facilitates the propagation of antibiotic resistance. However, the prediction or analytical determination of bioavailable concentrations of antibiotics in soil is still subject to great uncertainty. Biological assays are increasingly recognized as valuable complementary tools that allow a more direct determination of the residual antibiotic activity. This study assessed the bioavailability of structurally diverse antibiotics at a soil-water interface applying activity-based analyses in conjunction with equilibrium partitioning (EqP) modelling. The activity against gram-positive and gram-negative bacteria of nine antibiotics from different classes was determined in the presence and absence of standard soil (LUFA St. 2.2). The addition of soil affected the activity of different antibiotics to highly varying degrees. Moreover, a highly significant correlation (p<0.0001) between the experimentally observed and the EqP-derived log EC 50 values was observed. The innovative experimental design of this study provided new insights on the bioavailability of antibiotics at soil-water interfaces. EqP appears to be applicable to a broad range of antibiotics for the purpose of screening-level risk assessment. However, EqP estimates cannot replace soil-specific ecotoxicity testing in higher-tier assessments, since their accuracy is still compromised by a number of factors.

  15. Antibiotic activity of two Anabaena species against four fish ...

    African Journals Online (AJOL)

    ... cyanobacterial species (Anabaena solitaria, Anabaena variabilis, Anabaena cylindrical, Anabaena spiroides, Anabaena circinalis, Oscillatoria ornate, Oscillatoria salins, Oscillatoria tenuis, Oscillatoria rubescens and Oscillatoria prolifica) were investigated for their antibacterial activities against 4 fish pathogenic bacterial ...

  16. Cytotoxic and antifungal activities of melleolide antibiotics follow dissimilar structure-activity relationships.

    Science.gov (United States)

    Bohnert, Markus; Nützmann, Hans-Wilhelm; Schroeckh, Volker; Horn, Fabian; Dahse, Hans-Martin; Brakhage, Axel A; Hoffmeister, Dirk

    2014-09-01

    The fungal genus Armillaria is unique in that it is the only natural source of melleolide antibiotics, i.e., protoilludene alcohols esterified with orsellinic acid or its derivatives. This class of natural products is known to exert antimicrobial and cytotoxic effects. Here, we present a refined relationship between the structure and the antimicrobial activity of the melleolides. Using both agar diffusion and broth dilution assays, we identified the Δ(2,4)-double bond of the protoilludene moiety as a key structural feature for antifungal activity against Aspergillus nidulans, Aspergillus flavus, and Penicillium notatum. These findings contrast former reports on cytotoxic activities and may indicate a different mode of action towards susceptible fungi. We also report the isolation and structure elucidation of five melleolides (6'-dechloroarnamial, 6'-chloromelleolide F, 10-hydroxy-5'-methoxy-6'-chloroarmillane, and 13-deoxyarmellides A and B), along with the finding that treatment with an antifungal melleolide impacts transcription of A. nidulans natural product genes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. The degradation of antibiotic amoxicillin in the Fenton-activated sludge combined system.

    Science.gov (United States)

    Guo, Ruixin; Xie, Xiaodan; Chen, Jianqiu

    2015-01-01

    The present study investigated the removal efficiency of amoxicillin by the Fenton process, individual activated sludge process and Fenton-activated sludge combined system. For the antibiotic at 1 g L(-1), the optimal conditions of the Fenton process included: 4 mL FeSO4·7H2O solution (20.43 g  L(-1)), 6 mL H2O2 solution (3%) and 40°C. Under the optimal conditions, the removal rate of amoxicillin achieved up to 80% in 70 min. In addition, the impact of amoxicillin on microorganism limited the removal capacity of the activated sludge process. When the concentration of amoxicillin was less than 350 mg L(-1), 69.04-88.79% of the antibiotic was removed. However, the antibiotic could not be treated by the activated sludge when the concentration increased up to 650 mg L(-1). On the other hand, ifamoxicillin was pretreated partly by the Fenton process it was then degraded completely by the same activated sludge. Thus, the combined system included two steps: 80% amoxicillin was degraded in step I and was removed completely in the cheaper biological treatment (step II). Our result showed that compared with the individual activated sludge process, the Fenton process improved the removal capacity of the subsequent activated sludge process in the combined system.

  18. A40926, a new glycopeptide antibiotic with anti-Neisseria activity.

    OpenAIRE

    Goldstein, B P; Selva, E; Gastaldo, L; Berti, M; Pallanza, R; Ripamonti, F; Ferrari, P; Denaro, M; Arioli, V; Cassani, G

    1987-01-01

    In the course of a search for glycopeptide antibiotics having novel biological properties, we isolated A40926. Produced by an actinomycete of the genus Actinomadura, A40926 is a complex of four main factors which contain a fatty acid as part of a glycolipid attached to the peptide backbone. Its activity was, in most respects, similar to that of other glycopeptides, such as vancomycin and teicoplanin. However, in addition to inhibiting gram-positive bacteria, A40926 was very active against Nei...

  19. Occurrence of aminoglycoside-modifying enzymes genes (aac(6 ...

    African Journals Online (AJOL)

    Abstract. Background: Enzymatic modification of aminoglycosides is the primary mechanism of resistance by Pseudomonas aerug- inosa. Obejectives: We investigated the occurrence and mechanism of aminoglycosides resistance in P. aeruginosa isolates from hospitals in SouthWest Nigeria. Methods: A total of 54 ...

  20. Synergistic anti-Campylobacter jejuni activity of fluoroquinolone and macrolide antibiotics with phenolic compounds

    Directory of Open Access Journals (Sweden)

    Euna eOh

    2015-10-01

    Full Text Available The increasing resistance of Campylobacter to clinically-important antibiotics, such as fluoroquinolones and macrolides, is a serious public health problem. The objective of this study is to investigate synergistic anti-Campylobacter jejuni activity of fluoroquinolones and macrolides in combination with phenolic compounds. Synergistic antimicrobial activity was measured by performing a checkerboard assay with ciprofloxacin and erythromycin in the presence of 21 phenolic compounds. Membrane permeability changes in C. jejuni by phenolic compounds were determined by measuring the level of intracellular uptake of 1-N-phenylnaphthylamine (NPN. Antibiotic accumulation assays were performed to evaluate the level of ciprofloxacin accumulation in C. jejuni. Six phenolic compounds, including p-coumaric acid, sinapic acid, caffeic acid, vanillic acid, gallic acid, and taxifolin, significantly increased the susceptibility to ciprofloxacin and erythromycin in several human and poultry isolates. The synergistic antimicrobial effect was also observed in ciprofloxacin- and erythromycin-resistant C. jejuni strains. The phenolic compounds also substantially increased membrane permeability and antibiotic accumulation in C. jejuni. Interestingly, some phenolic compounds, such as gallic acid and taxifolin, significantly reduced the expression of the CmeABC multidrug efflux pump. Phenolic compounds increased the NPN accumulation in the cmeB mutant, indicating phenolic compounds may affect the membrane permeability. In this study, we successfully demonstrated that combinational treatment of C. jejuni with antibiotics and phenolic compounds synergistically inhibits C. jejuni by impacting both antimicrobial influx and efflux.

  1. Synthesis and Antibiotic Activity of Mebendazole Derivatives of Pharmacological Interest

    Directory of Open Access Journals (Sweden)

    Kavita Rathore

    2007-01-01

    Full Text Available Mebendazole is a well known anti-helimintic and belongs to the benzimidazole group of medicines. In order to achieve better medicinal results, i.e. enhanced activity and low toxicity, structural modifications are made in the existing drugs. Some 5-benzoyl-N-[1-(alkoxyphthalimido benzimidazol-2-yl] carbamic acid methyl ester (3a-c and 5-benzoyl-N-[1-(2,3-bis oxyphthalimido∕oxysuccinimido propyl benzimidazol-2-yl carbamic acid methyl ester (7a-b have been synthesized from two different routes. Structures of the compounds have been established on the basis of elemental analysis and spectral studies. All the synthesized compounds (3a-c and (7a-b were assayed in vitro for antimicrobial activity against mebendazole (itself and standard [ciprofloxacin (antibacterial and fluconazole (antifungal].

  2. Phenotypic Resistance to Disinfectants and Antibiotics in Methicillin-Resistant Staphylococcus aureus Strains Isolated from Pigs.

    Science.gov (United States)

    Espigares, E; Moreno Roldan, E; Espigares, M; Abreu, R; Castro, B; Dib, A L; Arias, Á

    2017-06-01

    The aim of this research was to study the phenotypic resistances to disinfectants and antibiotics in strains of methicillin-resistant Staphylococcus aureus (MRSA) obtained from Canary black pigs. Analyses were performed on 54 strains of MRSA, isolated in Canary black pigs from the province of Tenerife (Spain); all of them carried the mecA gene. The strains were isolated by means of nasal swab samples of healthy pigs, collected under veterinarian supervision. Bactericidal activity of antiseptics and disinfectants was tested by means of the dilution-neutralization method. Susceptibility to the disinfectants glutaraldehyde, peracetic acid and silver nitrate was assessed, as well as to the antiseptics chlorhexidine, benzalkonium chloride and povidone iodine. Susceptibility to a wide array of antibiotics representing the main groups was determined by means of the disc diffusion method. All the strains demonstrated susceptibility to the disinfectants tested at the recommended concentration, and even to dilutions equal to or lesser than 1/16. The most effective antiseptic and disinfectant were, respectively, chlorhexidine and silver nitrate. With regard to the antibiotics, the strains proved to be multiresistant. All presented phenotypic resistance to the β-lactam antibiotics ampicillin, penicillin and cefoxitin, as well as to numerous aminoglycosides, tetracycline and trimethoprim-sulfamethoxazole. It was also observed that 61.1% of the strains were carriers of plasmids. Our results underline that in the strains such as MRSA, which show multiple resistances to antibiotics, the antiseptics and disinfectants show great efficacy. Moreover, as other authors also suggest, for the treatment and prevention of infections caused by MRSA, the use of β-lactam and aminoglycoside antibiotics may be less effective. © 2016 Blackwell Verlag GmbH.

  3. Antibacterial Activity of Various Plants Extracts Against Antibiotic-resistant Aeromonas hydrophila.

    Science.gov (United States)

    Al Laham, Shaza Anwar; Al Fadel, Frdoos Mohammad

    2014-07-01

    Aeromonas hydrophila cause one of the most important diseases in fishes and lead to economic losses, and may be contaminated human beings. The current research aimed to investigate the anti-bacterial activity shown by the extracts prepared from different parts of Olea europea, Myrtus communis, Thymus vulgaris, Rosmarinuis officinalis, and Achillea falcata that grow in Syria against A. hydrophila that causes the most dangerous bacterial diseases in fish. THE STUDY WAS PERFORMED IN FOUR STAGES: First of all, the presence of A. hydrophila was investigated in 450 Samples of Cyprinus Carpio fish using blood agar, Trypticase soya agar, and Analytical Profile Index (API20E). Secondly, the plants extract was obtained using water, absolute alcohol, then ether using Soxhlet extraction apparatus and rotary vacuum evaporator. Thirdly, the antibacterial activity of some antibiotics on these bacteria was evaluated by disk diffusion method. Finally, the antibacterial effect of the extracts was determined by disk diffusion method. The studied antibiotics showed no antibacterial activity against these bacteria, except amikacin which had an acceptable effectiveness. However, the ethanol extracts of the studied plants revealed different antibacterial effects against A. hydrophila which showed antibiotic resistant. T. vulgaris extract had the strongest effect, whereas O. europea extract had the weakest activity. The water and ether petroleum extracts had no antibacterial activities. Ethanol extracts of the studied plants had different antibacterial effects against antibiotic-resistant A. hydrophila. T. vulgaris had the highest activity, R. officinalis had the second, and M. communis and A. falcate were in the third place, while the O. europea had the weakest antibacterial activity.

  4. In vitro activity of ceftaroline: A novel antibiotic against methicillin-resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Vaishali Gaikwad

    2016-01-01

    Full Text Available Introduction: Staphylococcus is one of the most common causes of nosocomial infection, especially pneumonia, surgical site infections, blood stream infections, and continues to be a major cause of community-acquired infections. The emergence of penicillin resistance followed by the development and spread of strains resistant to the semisynthetic penicillins such as methicillin, oxacillin and nafcillin, macrolides, tetracycline, and aminoglycosides has made the treatment of staphylococcal infection a global challenge. To treat this multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA, the only option available is glycopeptides such as vancomycin. However, recently, vancomycin-intermediate S. aureus and vancomycin-resistant S. aureus strains have emerged with different resistance mechanism. There are newer drugs in the pipeline against MRSA such as ceftaroline, dalbavancin, oritavancin, and tedizolid; however, very little data are available for their use. Recently, ceftaroline has been approved by the US Food and Drug Administration for the treatment of acute bacterial skin and soft tissue infections and community-acquired bacterial pneumonia due to MRSA. Hence, we tried to evaluate in vitro activity of ceftaroline against MRSA. Aim: The aim of this study was to detect in vitro activity of new cephalosporin, ceftaroline, against MRSA. Materials and Methods: Thirty nonduplicate MRSA strains were collected from various clinical samples, and minimum inhibitory concentration (MIC was detected using ceftaroline E-test strips. Results: Twenty-eight MRSA isolates (93.33% were found to be susceptible to ceftaroline. Conclusion: Ceftaroline demonstrated promising potency and coverage against MRSA isolates and can be considered an effective alternative treatment keeping vancomycin and linezolid as a reserved option.

  5. Activity of the thiopeptide antibiotic nosiheptide against contemporary strains of methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Haste, Nina M; Thienphrapa, Wdee; Tran, Dan N; Loesgen, Sandra; Sun, Peng; Nam, Sang-Jip; Jensen, Paul R; Fenical, William; Sakoulas, George; Nizet, Victor; Hensler, Mary E

    2012-12-01

    The rapid rise in antimicrobial resistance in bacteria has generated an increased demand for the development of novel therapies to treat contemporary infections, especially those caused by methicillin-resistant Staphylococcus aureus (MRSA). However, antimicrobial development has been largely abandoned by the pharmaceutical industry. We recently isolated the previously described thiopeptide antibiotic nosiheptide from a marine actinomycete strain and evaluated its activity against contemporary clinically relevant bacterial pathogens. Nosiheptide exhibited extremely potent activity against all contemporary MRSA strains tested including multiple drug-resistant clinical isolates, with MIC values 0.25 mg l(-1). Nosiheptide was also highly active against Enterococcus spp. and the contemporary hypervirulent BI/NAP1/027 strain of Clostridium difficile but was inactive against most Gram-negative strains tested. Time-kill analysis revealed nosiheptide to be rapidly bactericidal against MRSA in a concentration- and time-dependent manner, with a nearly 2-log kill noted at 6 h at 10 × MIC. Furthermore, nosiheptide was found to be non-cytotoxic against mammalian cells at >100 × MIC, and its anti-MRSA activity was not inhibited by 20% human serum. Notably, nosiheptide exhibited a significantly prolonged post-antibiotic effect against both healthcare- and community-associated MRSA compared with vancomycin. Nosiheptide also demonstrated in vivo activity in a murine model of MRSA infection, and therefore represents a promising antibiotic for the treatment of serious infections caused by contemporary strains of MRSA.

  6. MexY-promoted aminoglycoside resistance in Pseudomonas aeruginosa: involvement of a putative proximal binding pocket in aminoglycoside recognition.

    Science.gov (United States)

    Lau, Calvin Ho-Fung; Hughes, Daniel; Poole, Keith

    2014-04-22

    The resistance-nodulation-division (RND) family multidrug efflux system MexXY-OprM is a major determinant of aminoglycoside resistance in Pseudomonas aeruginosa, although the details of aminoglycoside recognition and export by MexY, the substrate-binding RND component of this efflux system, have not been elucidated. To identify regions/residues of MexY important for aminoglycoside resistance, plasmid-borne mexY was mutagenized and mutations that impaired MexY-promoted aminoglycoside (streptomycin) resistance were identified in a ΔmexY strain of P. aeruginosa. Sixty-one streptomycin-sensitive mexY mutants were recovered; among these, 7 unique mutations that yielded wild-type levels of MexY expression were identified. These mutations compromised resistance to additional aminoglycosides and to other antimicrobials and occurred in both the transmembrane and periplasmic regions of the protein. Mapping of the mutated residues onto a 3-dimensional structure of MexY modeled on Escherichia coli AcrB revealed that these tended to occur in regions implicated in general pump operation (transmembrane domain) and MexY trimer assembly (docking domain) and, thus, did not provide insights into aminoglycoside recognition. A region corresponding to a proximal binding pocket connected to a periplasm-linked cleft, part of a drug export pathway of AcrB, was identified in MexY and proposed to play a role in aminoglycoside recognition. To test this, selected residues (K79, D133, and Y613) within this pocket were mutagenized and the impact on aminoglycoside resistance was assessed. Mutations of D133 and Y613 compromised aminoglycoside resistance, while, surprisingly, the K79 mutation enhanced aminoglycoside resistance, confirming a role for this putative proximal binding pocket in aminoglycoside recognition and export. IMPORTANCE Bacterial RND pumps do not typically accommodate highly hydrophilic agents such as aminoglycosides, and it is unclear how those, such as MexY, which accommodate

  7. Antibacterial activities of silver nanoparticles and antibiotic-adsorbed silver nanoparticles against biorecycling microbes.

    Science.gov (United States)

    Khurana, Chandni; Vala, Anjana K; Andhariya, Nidhi; Pandey, O P; Chudasama, Bhupendra

    2014-09-20

    Silver nanoparticles have a huge share in nanotechnology based products used in clinical and hygiene products. Silver nanoparticles leaching from these medical and domestic products will eventually enter terrestrial ecosystems and will interact with the microbes present in the land and water. These interactions could be a threat to biorecycling microbes present in the Earth's crust. The antimicrobial action towards biorecycling microbes by leached silver nanoparticles from medical waste could be many times greater compared to that of silver nanoparticles leached from other domestic products, since medical products may contain traditional antibiotics along with silver nanoparticles. In the present article, we have evaluated the antimicrobial activities of as-synthesized silver nanoparticles, antibiotics - tetracycline and kanamycin, and antibiotic-adsorbed silver nanoparticles. The antimicrobial action of silver nanoparticles with adsorbed antibiotics is 33-100% more profound against the biorecycling microbes B. subtilis and Pseudomonas compared to the antibacterial action of silver nanoparticles of the same concentration. This study indicates that there is an immediate and urgent need for well-defined protocols for environmental exposure to silver nanoparticles, as the use of silver nanoparticles in nanotechnology based products is poorly restricted.

  8. Epilobi Hirsuti Herba Extracts Influence the In Vitro Activity of Common Antibiotics on Standard Bacteria

    Directory of Open Access Journals (Sweden)

    Pirvu Lucia

    2016-01-01

    Full Text Available Epilobium genus has been confirmed as an effective source of natural antimicrobials. However, the influence of Epilobi hirsuti herba derived products on usual antibiotics activity has not been studied. In this study, several standardized Epilobi hirsuti herba extracts (EHE were evaluated in order to asses their potential effects on usual antibiotics tested on standard Gram-positive and Gram-negative bacterial strains in vitro. The results emphasized that the bacterial strains ranged from sensitive (MIC values between 50–200 μg GAE mL-1 (S. epidermidis ATCC 12228 to very resistant (E. coli strains, E. faecalis ATCC 29212 being practically immune to EHE. In terms of synergistic interaction, Tetracycline and Ampicillin combinations lead to the most important stimulatory effects, the diameters of the inhibition zone being even 60% bigger compared to the antibiotic alone. Synergistic effects between myricetin(galloyl derivates and Tetracycline were also revealed on P. aeruginosa and E. coli strains. Together, it clearly demonstrated not only EHE’s own antimicrobial properties, but also their capacity to influence the antimicrobial potency of some common antibiotics. These results could be useful for the area of herbal medicines and as potential candidates in managing microbial resistance, but also for physicians and pharmacists using combined antibacterial therapy.

  9. Antibacterial Activity and Antibiotic-Enhancing Effects of Honeybee Venom against Methicillin-Resistant Staphylococcus aureus.

    Science.gov (United States)

    Han, Sang Mi; Kim, Joung Min; Hong, In Pyo; Woo, Soon Ok; Kim, Se Gun; Jang, He Rye; Pak, Sok Cheon

    2016-01-12

    Methicillin-resistant Staphylococcus aureus (MRSA), along with other antibiotic resistant bacteria, has become a significant social and clinical problem. There is thus an urgent need to develop naturally bioactive compounds as alternatives to the few antibiotics that remain effective. Here we assessed the in vitro activities of bee venom (BV), alone or in combination with ampicillin, penicillin, gentamicin or vancomycin, on growth of MRSA strains. The antimicrobial activity of BV against MRSA strains was investigated using minimum inhibitory concentrations (MIC), minimum bactericidal concentrations (MBC) and a time-kill assay. Expression of atl which encodes murein hydrolase, a peptidoglycan-degrading enzyme involved in cell separation, was measured by reverse transcription-polymerase chain reaction. The MICs of BV were 0.085 µg/mL and 0.11 µg/mL against MRSA CCARM 3366 and MRSA CCARM 3708, respectively. The MBC of BV against MRSA 3366 was 0.106 µg/mL and that against MRSA 3708 was 0.14 µg/mL. The bactericidal activity of BV corresponded to a decrease of at least 3 log CFU/g cells. The combination of BV with ampicillin or penicillin yielded an inhibitory concentration index ranging from 0.631 to 1.002, indicating a partial and indifferent synergistic effect. Compared to ampicillin or penicillin, both MRSA strains were more susceptible to the combination of BV with gentamicin or vancomycin. The expression of atl gene was increased in MRSA 3366 treated with BV. These results suggest that BV exhibited antibacterial activity and antibiotic-enhancing effects against MRSA strains. The atl gene was increased in MRSA exposed to BV, suggesting that cell division was interrupted. BV warrants further investigation as a natural antimicrobial agent and synergist of antibiotic activity.

  10. Antibacterial Activity and Antibiotic-Enhancing Effects of Honeybee Venom against Methicillin-Resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Sang Mi Han

    2016-01-01

    Full Text Available Methicillin-resistant Staphylococcus aureus (MRSA, along with other antibiotic resistant bacteria, has become a significant social and clinical problem. There is thus an urgent need to develop naturally bioactive compounds as alternatives to the few antibiotics that remain effective. Here we assessed the in vitro activities of bee venom (BV, alone or in combination with ampicillin, penicillin, gentamicin or vancomycin, on growth of MRSA strains. The antimicrobial activity of BV against MRSA strains was investigated using minimum inhibitory concentrations (MIC, minimum bactericidal concentrations (MBC and a time-kill assay. Expression of atl which encodes murein hydrolase, a peptidoglycan-degrading enzyme involved in cell separation, was measured by reverse transcription-polymerase chain reaction. The MICs of BV were 0.085 µg/mL and 0.11 µg/mL against MRSA CCARM 3366 and MRSA CCARM 3708, respectively. The MBC of BV against MRSA 3366 was 0.106 µg/mL and that against MRSA 3708 was 0.14 µg/mL. The bactericidal activity of BV corresponded to a decrease of at least 3 log CFU/g cells. The combination of BV with ampicillin or penicillin yielded an inhibitory concentration index ranging from 0.631 to 1.002, indicating a partial and indifferent synergistic effect. Compared to ampicillin or penicillin, both MRSA strains were more susceptible to the combination of BV with gentamicin or vancomycin. The expression of atl gene was increased in MRSA 3366 treated with BV. These results suggest that BV exhibited antibacterial activity and antibiotic-enhancing effects against MRSA strains. The atl gene was increased in MRSA exposed to BV, suggesting that cell division was interrupted. BV warrants further investigation as a natural antimicrobial agent and synergist of antibiotic activity.

  11. Antibiotic resistance and antibacterial activity in heterotrophic bacteria of mineral water origin.

    Science.gov (United States)

    Messi, Patrizia; Guerrieri, Elisa; Bondi, Moreno

    2005-06-15

    Antibiotic resistance and antibacterial activity were determined on heterotrophic bacteria isolated from mineral waters. Of the 120 isolates Pseudomonas spp. (55.8%) was the predominant group followed by Acinetobacter spp. (14.17%), Flavobacterium spp. (10.83%), Achromobacter spp. (10%), Burkholderia cepacia (3.3%), Agrobacterium/radiobacter (2.5%), Moraxella spp. (1.7%), Aeromonas hydrophila (1.7%). Over 80% of the isolates were resistant to one or more antibiotics and the highest resistance was found for chloramphenicol, ampicillin, colistin and sulfamethizole (60%, 55%, 50% and 47.5%, respectively). Strains with multiple antibiotic resistance (MAR) represented 55% of isolates and the most resistant organism belonged to the genus Pseudomonas. Of 40 randomly selected strains, 27 (67.5%) had antibacterial activity towards one or more indicators. This activity, found in a high percentage in the genus Pseudomonas (92%), emerged mainly against closely related microorganisms. Several producers were active also against Escherichia coli, Salmonella, Listeria monocytogenes and Staphylococcus aureus. Forty-six percent of the isolates harboured 1 to 5 plasmids with molecular weights ranging from 2.1 to 41.5 MDa.

  12. Mitochondrial 12S rRNA A827G mutation is involved in the genetic susceptibility to aminoglycoside ototoxicity

    International Nuclear Information System (INIS)

    Xing Guangqian; Chen Zhibin; Wei Qinjun; Tian Huiqin; Li Xiaolu; Zhou Aidong; Bu Xingkuan; Cao Xin

    2006-01-01

    We have analyzed the clinical and molecular characterization of a Chinese family with aminoglycoside-induced and non-syndromic hearing impairment. Clinical evaluations revealed that only those family members who had a history of exposure to aminoglycoside antibiotics subsequently developed hearing loss, suggesting mitochondrial genome involvement. Sequence analysis of the mitochondrial 12S rRNA and tRNA Ser(UCN) genes led to the identification of a homoplasmic A827G mutation in all maternal relatives, a mutation that was identified previously in a few sporadic patients and in another Chinese family with non-syndromic deafness. The pathogenicity of the A827G mutation is strongly supported by the occurrence of the same mutation in two independent families and several genetically unrelated subjects. The A827G mutation is located at the A-site of the mitochondrial 12S rRNA gene which is highly conserved in mammals. It is possible that the alteration of the tertiary or quaternary structure of this rRNA by the A827G mutation may lead to mitochondrial dysfunction, thereby playing a role in the pathogenesis of hearing loss and aminoglycoside hypersensitivity. However, incomplete penetrance of hearing impairment indicates that the A827G mutation itself is not sufficient to produce clinical phenotype but requires the involvement of modifier factors for the phenotypic expression. Indeed, aminoglycosides may contribute to the phenotypic manifestation of the A827G mutation in this family. In contrast with the congenital or early-onset hearing impairment in another Chinese family carrying the A827G mutation, three patients in this pedigree developed hearing loss only after use of aminoglycosides. This discrepancy likely reflects the difference of genetic backgrounds, either mitochondrial haplotypes or nuclear modifier genes, between two families

  13. Dithiolopyrrolones: biosynthesis, synthesis, and activity of a unique class of disulfide-containing antibiotics.

    Science.gov (United States)

    Li, Bo; Wever, Walter J; Walsh, Christopher T; Bowers, Albert A

    2014-07-01

    Covering: up to 2014. Dithiolopyrrolone (DTP) group antibiotics were first isolated in the early half of the 20th century, but only recently has research been reawakened by insights gained from the synthesis and biosynthesis of this structurally intriguing class of molecules. DTPs are characterized by an electronically unique bicyclic structure, which contains a compact disulfide bridge between two ene-thiols. Points of diversity within the compound class occur outside of the bicyclic core, at the two amide nitrogens. Such modifications distinguish three of the most well studied members of the class, holomycin, thiolutin, and aureothricin; the DTP core has also more recently been identified in the marine antibiotic thiomarinol, in which it is linked to a marinolic acid moiety, analog of the FDA-approved topical antibiotic Bactroban® (GlaxoSmithKline). Dithiolopyrrolones exhibit relatively broad-spectrum antibiotic activity against many Gram-positive and Gram-negative bacteria, as well as strains of Mycobacterium tuberculosis. Additionally, they have been shown to exhibit potent and selective anti-cancer activity. Despite this promising profile, there is still much unknown about the mechanisms of action for DTPs. Early reports suggested that they inhibit yeast growth at the level of transcription and that this effect is largely responsible for their distinctive microbial static properties; a similar mechanism is supported in bacteria. Elucidation of biosynthetic pathways for holomycin in Streptomyces clavuligerus and Yersinia ruckeri and thiomarinol in Alteromonas rava sp. nov. SANK 73390, have contributed evidence suggesting that multiple mechanisms may be operative in the activity of these compounds. This review will comprehensively cover the history and development of dithiolopyrrolones with particular emphasis on the biosynthesis, synthesis, biological activity and mechanism of action.

  14. In vivo antibacterial activity and pharmacological properties of the membrane-active glycopeptide antibiotic YV11455.

    Science.gov (United States)

    Yarlagadda, Venkateswarlu; Konai, Mohini M; Manjunath, Goutham B; Prakash, Relekar G; Mani, Bhuvana; Paramanandham, Krishnamoorthy; Ranjan, Shome B; Ravikumar, Raju; Chakraborty, Subhankari P; Roy, Somenath; Haldar, Jayanta

    2015-06-01

    The membrane-active glycopeptide antibiotic YV11455 is a lipophilic cationic vancomycin analogue that demonstrates rapid and concentration-dependent killing of clinically relevant multidrug-resistant (MDR) Gram-positive bacteria in vitro. YV11455 was 2-fold and 54-270-fold more effective than vancomycin against clinical isolates of vancomycin-sensitive and vancomycin-resistant bacteria, respectively. In this study, the in vivo efficacy, pharmacodynamics, pharmacokinetics and acute toxicology of YV11455 were investigated. In vivo activity and pharmacodynamics were determined in the neutropenic mouse thigh infection model against meticillin-resistant Staphylococcus aureus (MRSA). YV11455 produced dose-dependent reductions in MRSA titres in thigh muscle. When administered intravenously, the 50% effective dose (ED(50)) for YV11455 against MRSA was found to be 3.3 mg/kg body weight, and titres were reduced by up to ca. 3log(10)CFU/g from pre-treatment values at a dosage of 12 mg/kg with single treatment. Single-dose pharmacokinetic studies demonstrated linear kinetics and a prolonged half-life, with an increase in drug exposure (area under the concentration-time curve) compared with vancomycin. The peak plasma concentration following an intravenous dose of 12 mg/kg was 543.5 μg/mL. Acute toxicology studies revealed that YV11455 did not cause any significant alterations in biochemical parameters or histological pictures related to major organs such as the liver and kidney at its pharmacodynamic endpoint (ED(3-log kill)). These findings collectively suggest that YV11455 could be used clinically for the treatment of infections caused by MDR Gram-positive bacteria. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  15. Polycyclic Polyprenylated Acylphloroglucinols: An Emerging Class of Non-Peptide-Based MRSA- and VRE-Active Antibiotics.

    Science.gov (United States)

    Guttroff, Claudia; Baykal, Aslihan; Wang, Huanhuan; Popella, Peter; Kraus, Frank; Biber, Nicole; Krauss, Sophia; Götz, Friedrich; Plietker, Bernd

    2017-12-11

    In the past 20 years, peptide-based antibiotics, such as vancomycin, teicoplanin, and daptomycin, have often been considered as second-line antibiotics. However, in recent years, an increasing number of reports on vancomycin resistance in pathogens appeared, which forces researchers to find novel lead structures for potent new antibiotics. Herein, we report the total synthesis of a defined endo-type B PPAP library and their antibiotic activity against multiresistant S. aureus and various vancomycin-resistant Enterococci. Four new compounds that combine high activities and low cytotoxicity were identified, indicating that the PPAP core might become a new non-peptide-based lead structure in antibiotic research. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Diminished Antimicrobial Peptide and Antifungal Antibiotic Activities against Candida albicans in Denture Adhesive

    Directory of Open Access Journals (Sweden)

    Amber M. Bates

    2017-02-01

    Full Text Available The underlying causes of denture stomatitis may be related to the long-term use of adhesives, which may predispose individuals to oral candidiasis. In this study, we hypothesize that antimicrobial peptides and antifungal antibiotics have diminished anti-Candida activities in denture adhesive. To show this, nine antimicrobial peptides and five antifungal antibiotics with and without 1.0% denture adhesive were incubated with Candida albicans strains ATCC 64124 and HMV4C in radial diffusion assays. In gels with 1.0% adhesive, HNP-1, HBD2, HBD3, IP-10, LL37 (only one strain, histatin 5 (only one strain, lactoferricin B, and SMAP28 showed diminished activity against C. albicans. In gels with 1.0% adhesive, amphotericin B and chlorhexidine dihydrochloride were active against both strains of C. albicans. These results suggest that denture adhesive may inactivate innate immune mediators in the oral cavity increasing the risk of C. albicans infections, but inclusion of antifungal antibiotics to denture adhesive may aid in prevention or treatment of Candida infections and denture stomatitis.

  17. Antagonistic activity of antibiotic producing Streptomyces sp. against fish and human pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Nazmul Hossain

    2014-04-01

    Full Text Available In this study, attempts were made to isolate Streptomyces sp. from soil samples of two different regions of Bangladesh and evaluate their antagonistic activity against fish and human pathogenic bacteria. A total of 10 isolates were identified as Streptomyces sp. based on several morphological, physiological and biochemical tests. Cross streak method was used to observe the antagonistic activity of the Streptomyces sp. isolates against different fish pathogens belonging to the genus Aeromonas, Pseudomonas and Edwardsiella and human clinical isolates belonging to the genus Klebsiella, Salmonella and Streptococcus. Seven Streptomyces sp. isolates showed antagonism against both fish and human pathogenic bacteria. Four isolates viz., N24, N26, N28 and N47 showed broad spectrum of antagonistic activity (80-100% against all genera of fish and human pathogenic bacteria. The isolate N49 exhibited highest spectrum of antagonism against all fish pathogens (90-100% but comparatively lower degree of antagonism against human pathogens (50-60%. Rest of the two isolates (N21 and N23 showed variability in their antagonism. Results showed that broad spectrum antibiotic(s could be developed from the isolates N24, N26, N28 and N47against several human and fish pathogens. The isolate N49 could be a potential source of antibiotic, especially for fish pathogenic bacteria.

  18. Antimicrobial activity of filamentous fungi isolated from highly antibiotic-contaminated river sediment

    Science.gov (United States)

    Svahn, K. Stefan; Göransson, Ulf; El-Seedi, Hesham; Bohlin, Lars; Larsson, D.G. Joakim; Olsen, Björn; Chryssanthou, Erja

    2012-01-01

    Background Filamentous fungi are well known for their production of substances with antimicrobial activities, several of which have formed the basis for the development of new clinically important antimicrobial agents. Recently, environments polluted with extraordinarily high levels of antibiotics have been documented, leading to strong selection pressure on local sentinel bacterial communities. In such microbial ecosystems, where multidrug-resistant bacteria are likely to thrive, it is possible that certain fungal antibiotics have become less efficient, thus encouraging alternative strategies for fungi to compete with bacteria. Methods In this study, sediment of a highly antibiotic-contaminated Indian river was sampled in order to investigate the presence of cultivable filamentous fungi and their ability to produce substances with antimicrobial activity. Results Sixty one strains of filamentous fungi, predominantly various Aspergillus spp. were identified. The majority of the Aspergillus strains displayed antimicrobial activity against methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase-producing Escherichia coli, vancomycin-resistant Enterococcus faecalis and Candida albicans. Bioassay-guided isolation of the secondary metabolites of A. fumigatus led to the identification of gliotoxin. Conclusion This study demonstrated proof of principle of using bioassay-guided isolation for finding bioactive molecules. PMID:22957125

  19. Impact of galacto-oligosaccharides on the gut microbiota composition and metabolic activity upon antibiotic treatment during in vitro fermentation.

    Science.gov (United States)

    Ladirat, Stephanie E; Schuren, Frank H J; Schoterman, Margriet H C; Nauta, Arjen; Gruppen, Harry; Schols, Henk A

    2014-01-01

    Prebiotics are considered to have potential to reduce disturbances in the gut microbiota induced by antibiotics. Results in literature are, however, not consistent. The current in vitro study conducted in a fermentation screening platform allowed to unambiguously compare the impact of galacto-oligosaccharides (GOS) on adult gut microbiota composition and activity upon treatment with four antibiotics at two doses. The changes in relative abundance of bacteria upon antibiotic treatment and the growth of Bifidobacterium and Lactobacillus upon GOS addition were antibiotic and dose dependent. This conclusion explains discrepancies in literature and indicates that particular combinations of GOS antibiotic should be studied. The combination GOS-Amoxicillin was especially of interest as, after decrease in Bifidobacterium levels, a recovery of mainly Bifidobacterium longum was observed and could be correlated with specific degradation patterns of GOS. Next to different degradation profiles of individual GOS, an accumulation of monosaccharides and intermediate organic acids was observed in antibiotic-treated microbiota as compared to nontreated microbiota. This showed that although GOS were utilized and beneficial bacteria could grow in 3 of 4 antibiotics tested, the metabolic activity of an antibiotic-treated microbiota was still disturbed as compared to the nontreated microbiota. © 2013 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

  20. β-lactam antibiotic-induced release of lipoteichoic acid from Staphylococcus aureus leads to activation of neutrophil granulocytes

    Directory of Open Access Journals (Sweden)

    Hartung Thomas

    2006-06-01

    Full Text Available Abstract Background Polymorphonuclear neutrophil granulocytes (PMN are phagocytes of the first line of antimicrobial defense. Previously we demonstrated that lipoteichoic acid (LTA from Staphylococcus aureus (S. aureus directly activates neutrophil granulocytes. Others have reported that exposure of S. aureus to β-lactam antibiotics leads to LTA release. In the present study we addressed the question whether exposure of S. aureus to β-lactam antibiotics or antibiotics of other groups results in the generation of PMN-stimulating activity and whether this activity can be attributed to LTA. Methods S. aureus were exposed to flucloxacillin, a β-lactam antibiotic or to the protein synthesis-inhibitors erythromycin and gentamicin, or to ciprofloxacin, a gyrase inhibitor. Supernatants of the antibiotic-treated bacteria were assayed for their LTA content and for their effect on PMN functions. Results We observed that exposure of S. aureus to flucloxacillin and, to a lesser degree to ciprofloxacin, but not to erythromycin or gentamicin led to LTA release. Co-incubation of neutrophil granulocytes with LTA-containing supernatants led to PMN activation as assed by morphological changes, release of IL-8, delay of spontaneous apoptosis and enhanced phagocytic activity. Depletion of LTA from the supernatants markedly reduced their PMN-activating capacity. Conclusion The findings suggest that, via the activation of PMN, antibiotic-induced LTA release from S. aureus leads to enhanced antimicrobial activity of the innate immune defense mechanisms.

  1. A two-component regulatory system interconnects resistance to polymyxins, aminoglycosides, fluoroquinolones, and β-lactams in Pseudomonas aeruginosa.

    Science.gov (United States)

    Muller, Cédric; Plésiat, Patrick; Jeannot, Katy

    2011-03-01

    Constitutive overexpression of the active efflux system MexXY/OprM is a major cause of resistance to aminoglycosides, fluoroquinolones, and cefepime in clinical strains of Pseudomonas aeruginosa. Upregulation of this pump often results from mutations occurring in mexZ, the local repressor gene of the mexXY operon. In this study, analysis of MexXY-overproducing mutants selected in vitro from reference strain PAO1Bes on amikacin (at a concentration 1.5-fold higher than the MIC) led to identification of a new class of mutants harboring an intact mexZ gene and exhibiting increased resistance to colistin and imipenem in addition to aminoglycosides, fluoroquinolones, and cefepime. Reverse transcription-quantitative PCR (RT-qPCR) experiments on a selected clone named PAOW2 demonstrated that mexXY overexpression was independent of mexZ and the PA5471 gene, which is required for drug-dependent induction of mexXY. Furthermore, the transcript levels of the oprD gene, which encodes the carbapenem-selective porin OprD, were found to be reduced drastically in PAOW2. Whole-genome sequencing revealed a single mutation resulting in an M59I substitution in the ParR protein, the response regulator of the ParRS two-component regulatory system (with ParS being the sensor kinase), which is required for adaptive resistance of P. aeruginosa to polycationic peptides such as colistin. The multidrug resistance phenotype was suppressed in PAOW2 by deletion of the parS and parRS genes and conferred to PAO1Bes by chromosomal insertion of the mutated parRS locus from PAOW2. As shown by transcriptomic analysis, only a very small number of genes were expressed differentially between PAOW2 and PAO1Bes, including the lipopolysaccharide (LPS) modification operon arnBCADTEF-ugd, responsible for resistance to polycationic agents. Exposure of wild-type PAO1Bes to different polycationic peptides, including colistin, was shown to result in increased mexY and repressed oprD expression via Par

  2. Plasmid metagenome reveals high levels of antibiotic resistance genes and mobile genetic elements in activated sludge.

    Directory of Open Access Journals (Sweden)

    Tong Zhang

    Full Text Available The overuse or misuse of antibiotics has accelerated antibiotic resistance, creating a major challenge for the public health in the world. Sewage treatment plants (STPs are considered as important reservoirs for antibiotic resistance genes (ARGs and activated sludge characterized with high microbial density and diversity facilitates ARG horizontal gene transfer (HGT via mobile genetic elements (MGEs. However, little is known regarding the pool of ARGs and MGEs in sludge microbiome. In this study, the transposon aided capture (TRACA system was employed to isolate novel plasmids from activated sludge of one STP in Hong Kong, China. We also used Illumina Hiseq 2000 high-throughput sequencing and metagenomics analysis to investigate the plasmid metagenome. Two novel plasmids were acquired from the sludge microbiome by using TRACA system and one novel plasmid was identified through metagenomics analysis. Our results revealed high levels of various ARGs as well as MGEs for HGT, including integrons, transposons and plasmids. The application of the TRACA system to isolate novel plasmids from the environmental metagenome, coupled with subsequent high-throughput sequencing and metagenomic analysis, highlighted the prevalence of ARGs and MGEs in microbial community of STPs.

  3. Plasmid metagenome reveals high levels of antibiotic resistance genes and mobile genetic elements in activated sludge.

    Science.gov (United States)

    Zhang, Tong; Zhang, Xu-Xiang; Ye, Lin

    2011-01-01

    The overuse or misuse of antibiotics has accelerated antibiotic resistance, creating a major challenge for the public health in the world. Sewage treatment plants (STPs) are considered as important reservoirs for antibiotic resistance genes (ARGs) and activated sludge characterized with high microbial density and diversity facilitates ARG horizontal gene transfer (HGT) via mobile genetic elements (MGEs). However, little is known regarding the pool of ARGs and MGEs in sludge microbiome. In this study, the transposon aided capture (TRACA) system was employed to isolate novel plasmids from activated sludge of one STP in Hong Kong, China. We also used Illumina Hiseq 2000 high-throughput sequencing and metagenomics analysis to investigate the plasmid metagenome. Two novel plasmids were acquired from the sludge microbiome by using TRACA system and one novel plasmid was identified through metagenomics analysis. Our results revealed high levels of various ARGs as well as MGEs for HGT, including integrons, transposons and plasmids. The application of the TRACA system to isolate novel plasmids from the environmental metagenome, coupled with subsequent high-throughput sequencing and metagenomic analysis, highlighted the prevalence of ARGs and MGEs in microbial community of STPs.

  4. Lethal inflammasome activation by a multi-drug resistant pathobiont upon antibiotic disruption of the microbiota

    Science.gov (United States)

    Ayres, Janelle S.; Trinidad, Norver J.; Vance, Russell E.

    2012-01-01

    The mammalian intestine harbors a complex microbial community that provides numerous benefits to its host. However, the microbiota can also include potentially virulent species, termed pathobionts, which can cause disease when intestinal homeostasis is disrupted. The molecular mechanisms by which pathobionts cause disease remain poorly understood. Here we describe a sepsis-like disease that occurs upon gut injury in antibiotic-treated mice. Sepsis was associated with the systemic spread of a specific multidrug-resistant E. coli pathobiont that expanded dramatically in the microbiota of antibiotic-treated mice. Rapid sepsis-like death required a component of the innate immune system, the Naip5-Nlrc4 inflammasome. In accordance with Koch's postulates, we found the E. coli pathobiont was sufficient to activate Naip5-Nlrc4 and cause disease when injected intravenously into unmanipulated mice. These findings reveal how sepsis-like disease can result from recognition of pathobionts by the innate immune system. PMID:22522562

  5. Once-daily versus multiple-daily dosing with intravenous aminoglycosides for cystic fibrosis.

    Science.gov (United States)

    Smyth, Alan R; Bhatt, Jayesh; Nevitt, Sarah J

    2017-03-27

    People with cystic fibrosis, who are chronically colonised with the organism Pseudomonas aeruginosa, often require multiple courses of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations. The properties of aminoglycosides suggest that they could be given in higher doses less often. This is an update of a previously published review. To assess the effectiveness and safety of once-daily versus multiple-daily dosing of intravenous aminoglycoside antibiotics for the management of pulmonary exacerbations in cystic fibrosis. We searched the Cystic Fibrosis Specialist Register held at the Cochrane Cystic Fibrosis and Genetic Disorders Group's editorial base, comprising references identified from comprehensive electronic database searches, handsearching relevant journals and handsearching abstract books of conference proceedings.Date of the most recent search: 24 June 2016. All randomised controlled trials, whether published or unpublished, in which once-daily dosing of aminoglycosides has been compared with multiple-daily dosing in terms of efficacy or toxicity or both, in people with cystic fibrosis. The two authors independently selected the studies to be included in the review and assessed the risk of bias of each study; authors also assessed the quality of the evidence using the GRADE criteria. Data were independently extracted by each author. Authors of the included studies were contacted for further information. As yet unpublished data were obtained for one of the included studies. Fifteen studies were identified for possible inclusion in the review. Four studies reporting results from a total of 328 participants (aged 5 to 50 years) were included in this review. All studies compared once-daily dosing with thrice-daily dosing. One study had a low risk of bias for all criteria assessed; the remaining three included studies had a high risk of bias from blinding, but for other criteria were judged to have either an unclear or a low risk

  6. Study on a new antifungal antibiotic, yimeimycin--isolation, structure elucidation and biological activities

    International Nuclear Information System (INIS)

    Shi Yuefeng; Sang Jinlong; Zhu Lihong; Li Xiaohui; Wu Jian

    2004-01-01

    Strain HA-8416, the producer of yimeimycin, was isolated from a soil sample collected in Hangzhou, Zhejiang province, China. Based on the investigation of morphological, cultural, physiological and biochemical characteristic as well as the cell wall chemical composition, strain HA8416 is extremely similar to Streptomyces hygrospinosus SF-104, and named Streptomyces hygrospinosus var tianmushanensis n. var. Sand et al. By means of spectroscopic analysis (UV, 1 H-NMR, DEPT CNMR and H-H COSY), yimeimycin was identified as a new antibiotic of the nucleoside family. Yimeimeycin appeared no activities against G + /G-bacteria, but was active against the fungi, Sphaerotheca cucurbitae, Pellicularia sasakii, Colletotrichum orbiculare, especially

  7. Enhancing activity of antibiotics against Staphylococcus aureus: Zanthoxylum capense constituents and derivatives.

    Science.gov (United States)

    Cabral, Vanessa; Luo, Xuan; Junqueira, Elisabete; Costa, Sofia S; Mulhovo, Silva; Duarte, Aida; Couto, Isabel; Viveiros, Miguel; Ferreira, Maria-José U

    2015-04-15

    Six compounds (1-6), isolated from the methanol extract of the roots of the African medicinal plant Zanthoxylum capense Thunb. (Rutaceae), and seven ester derivatives (7-13) were evaluated for their antibacterial activities and modulatory effects on the MIC of antibiotics (erythromycin, oxacillin, and tetracycline) and ethidium bromide (EtBr) against a Staphylococcus aureus reference strain (ATCC 6538). Using the same model, compounds 1-13 were also assessed for their potential as efflux pump inhibitors by a fluorometric assay that measures the accumulation of the broad range efflux pump substrate EtBr. Compounds 8 and 11 were further evaluated for their antibacterial, modulatory and EtBr accumulation effects against four additional S. aureus strains, which included two clinical methicillin-resistant S. aureus (MRSA) strains. Compounds (1-13) have not shown antibacterial activity at the concentration ranges tested. When evaluated against S. aureus ATCC 6538, oxychelerythrine (1) a benzophenanthridine alkaloid, showed the highest modulatory activity enhancing the susceptibility of this strain to all the tested antibiotics from two to four-fold. Ailanthoidiol diacetate (8) and ailanthoidiol di-2-ethylbutanoate (11) were also good modulators when combined with EtBr, increasing the bacteria susceptibility by four and two-fold, respectively. In the EtBr accumulation assay, using ATCC 6538 strain, the phenylpropanoid (+)-ailanthoidiol (6) and most of its ester derivatives (8-11) exhibited higher activity than the positive control verapamil. The highest effects were found for compounds 8 and 11 that also increased the accumulation of EtBr, using S. aureus ATCC 25923 as model. Furthermore, both compounds (8, 11) were able to enhance the ciprofloxacin activity against the MRSA clinical strains tested, causing a reduction of the antibiotic MIC values from two to four-fold. The EtBr accumulation assay revealed that this modulation activity was not due to an inhibition of

  8. Isolation, Phylogenetic Analysis and Antibiotic Activity Screening of Red Sea Sponge-Associated Actinobacteria

    KAUST Repository

    Yang, Chen

    2013-06-01

    Infectious disease has always been and will continue to be a heavy burden on human society worldwide. Terrestrial actinobacteria, notable as a source of antibiotics, have been well investigated in the past. In constrast, marine actinobacteria, especially sponge-associated species, have received much less attention and isolates are sparse. With the aim of studying and discovering novel marine actinobacteria, 11 different species of sponges were collected from the Central Red Sea in Saudi Arabia and cultured with three different types of media. 16S rRNA gene-sequencing revealed that among all 75 isolated bacterial strains 13 belonged to the order actinomycetales. These 13 actinomycetes fall into four different families and can be assigned to six different genera. Antibiotic activity tests using disc diffusion assay were performed against Gram-positive bacteria (Bacillus sp.), Gram-negative bacteria (Escherichia coli), fungi (Fusarium sp.) and West Nile virus NS3 protease. Nine strains presented different level of bioactivity against these pathogens. These findings provide evidence that actinomycetes are presented in marine sponges and that they have the potential to be good candidates in the search for new effective antibiotic, antifungal, and antiviral compounds.

  9. Eliciting antibiotics active against the ESKAPE pathogens in a collection of actinomycetes isolated from mountain soils.

    Science.gov (United States)

    Zhu, Hua; Swierstra, Jasper; Wu, Changsheng; Girard, Geneviève; Choi, Young Hae; van Wamel, Willem; Sandiford, Stephanie K; van Wezel, Gilles P

    2014-08-01

    The rapid emergence of multidrug-resistant (MDR) bacterial pathogens poses a major threat for human health. In recent years, genome sequencing has unveiled many poorly expressed antibiotic clusters in actinomycetes. Here, we report a well-defined ecological collection of >800 actinomycetes obtained from sites in the Himalaya and Qinling mountains, and we used these in a concept study to see how efficiently antibiotics can be elicited against MDR pathogens isolated recently from the clinic. Using 40 different growth conditions, 96 actinomycetes were identified - predominantly Streptomyces - that produced antibiotics with efficacy against the MDR clinical isolates referred to as ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and/or Enterobacter cloacae. Antimicrobial activities that fluctuated strongly with growth conditions were correlated with specific compounds, including borrelidin, resistomycin, carbomethoxy-phenazine, and 6,7,8- and 5,6,8-trimethoxy-3-methylisocoumarin, of which the latter was not described previously. Our work provided insights into the potential of actinomycetes as producers of drugs with efficacy against clinical isolates that have emerged recently and also underlined the importance of targeting a specific pathogen. © 2014 The Authors.

  10. Antibiotic activity of the extract of Punica granatum Linn. over bovine strains of Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Maria A. R. Silva

    Full Text Available Human and veterinary medicines have not been so well succeeded in order to achieving their goals concerning the treatment of infections for long term caused by Staphylococcus aureus linked to resistance development against antibiotic agents. The antibiotic activity of the Punica granatum Linn. fresh fruit pericarp extract was evaluated by the agar diffusion method on 38 S. aureus strains, isolated from apparently healthy lactating cows in farms situated in counties of the semi-arid region of the State of Paraíba, Brazil to determine the minimum inhibitory concentration (MIC. Twenty-two of the thirty-eight strains are penicillin-resistant (PRSA. The extract of P. granatum presented potential antibiotic action over all the assayed strains, forming 10 to 36 mm diameter inhibition zones. This paper's results claim the effectiveness of the extract of P. granatum as a potential antibacterial agent on S. aureus, and display the significance of evaluating new substances with antimicrobial potential, which can contribute to alternative therapeutics for veterinary and medicine.

  11. Activity and selectivity of histidine-containing lytic peptides to antibiotic-resistant bacteria.

    Science.gov (United States)

    Kharidia, Riddhi; Tu, Zhigang; Chen, Long; Liang, Jun F

    2012-09-01

    Lytic peptides are a group of membrane-acting peptides that are active to antibiotic-resistant bacteria but demonstrate high toxicity to tissue cells. Here, we reported the construction of new lytic peptide derivatives through the replacement of corresponding lysine/arginine residues in lytic peptide templates with histidines. Resulting lytic peptides had the same lethality to antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus, but showed greatly improved selectivity to bacteria. When incubated with co-cultured bacteria and tissue cells, these histidine-containing lytic peptide derivatives killed bacteria selectively but spared co-cultured human cells. Membrane insertion and peptide-quenching studies revealed that histidine protonation controlled peptide interactions with cell membranes determined the bacterial selectivity of lytic peptide derivatives. Compared with parent peptides, lytic peptide derivatives bound to bacteria strongly and inserted deeply into the bacterial cell membrane. Therefore, histidine-containing lytic peptides represent a new group of antimicrobial peptides for bacterial infections in which the antibiotic resistance has developed.

  12. Structure of the bifunctional aminoglycoside-resistance enzyme AAC(6')-Ie-APH(2'')-Ia revealed by crystallographic and small-angle X-ray scattering analysis.

    Science.gov (United States)

    Smith, Clyde A; Toth, Marta; Weiss, Thomas M; Frase, Hilary; Vakulenko, Sergei B

    2014-10-01

    Broad-spectrum resistance to aminoglycoside antibiotics in clinically important Gram-positive staphylococcal and enterococcal pathogens is primarily conferred by the bifunctional enzyme AAC(6')-Ie-APH(2'')-Ia. This enzyme possesses an N-terminal coenzyme A-dependent acetyltransferase domain [AAC(6')-Ie] and a C-terminal GTP-dependent phosphotransferase domain [APH(2'')-Ia], and together they produce resistance to almost all known aminoglycosides in clinical use. Despite considerable effort over the last two or more decades, structural details of AAC(6')-Ie-APH(2'')-Ia have remained elusive. In a recent breakthrough, the structure of the isolated C-terminal APH(2'')-Ia enzyme was determined as the binary Mg2GDP complex. Here, the high-resolution structure of the N-terminal AAC(6')-Ie enzyme is reported as a ternary kanamycin/coenzyme A abortive complex. The structure of the full-length bifunctional enzyme has subsequently been elucidated based upon small-angle X-ray scattering data using the two crystallographic models. The AAC(6')-Ie enzyme is joined to APH(2'')-Ia by a short, predominantly rigid linker at the N-terminal end of a long α-helix. This α-helix is in turn intrinsically associated with the N-terminus of APH(2'')-Ia. This structural arrangement supports earlier observations that the presence of the intact α-helix is essential to the activity of both functionalities of the full-length AAC(6')-Ie-APH(2'')-Ia enzyme.

  13. Combination antibiotic therapy for the treatment of infective endocarditis due to enterococci.

    Science.gov (United States)

    Leone, Sebastiano; Noviello, Silvana; Esposito, Silvano

    2016-06-01

    Enterococci are common causes of infective endocarditis (IE) in both health care and community-based setting. Enterococcal IE requires bactericidal therapy for an optimal outcome. For decades, cell-wall-active antimicrobial agents (penicillins or vancomycin) in combination with aminoglycosides were the cornerstone of the treatment; however, the emergence of antibiotic resistance has significantly reduced the efficacy of these regimens. Data for this review were identified by searches of MEDLINE and references from relevant articles on antibiotic combination regimens for the treatment of enterococcal IE. Abstracts presented in scientific conferences were not searched for. New effective and safe combination treatments, including double-β-lactam and daptomycin/β-lactam combination, are proving useful for the management of IE due to enterococci.

  14. Syzygium jambos Displayed Antibacterial and Antibiotic-Modulating Activities against Resistant Phenotypes

    Directory of Open Access Journals (Sweden)

    Brice E. N. Wamba

    2018-01-01

    Full Text Available The present study was designed to evaluate the antibacterial activities of methanol extracts of bark and leaves of Syzygium jambos, as well as their synergistic effects with selected antibiotics against drug-resistant Gram-positive and Gram-negative bacteria. The crude extracts were subjected to qualitative phytochemical screening; broth microdilution method was used for antibacterial assays. Phytochemical studies indicate that leaves and bark extracts contained polyphenols, anthraquinones, tannins, and steroids. Extract of the leaves was active against all the 26 strains of Staphylococcus aureus and all the 21 strains of Gram-negative bacteria tested, within the minimum inhibitory concentration (MIC range of 32–512 μg/mL. The lowest MIC value of 32 μg/mL was obtained with extract of the leaves against Staphylococcus aureus MRSA9 strain. In Gram-negative bacteria, the lowest MIC value of 64 μg/mL was also obtained against Enterobacter aerogenes EA294 and Klebsiella pneumoniae K24 strains. Against S. aureus strains, antibiotic-modulating activity of extracts at MIC/2 towards more than 70% of the tested strains was obtained when leaves and bark extracts were tested in association with chloramphenicol (CHL. This was also the case when leaves extract was combined with CHL, kanamycin (KAN, tetracycline (TET, and erythromycin (ERY and when bark extract was combined with ciprofloxacin (CIP, TET, and ERY against Gram-negative bacteria. In conclusion, this study demonstrated that Syzygium jambos has antibacterial and antibiotic-modulating activities.

  15. Discovery and Biosynthesis of Gladiolin: A Burkholderia gladioli Antibiotic with Promising Activity against Mycobacterium tuberculosis.

    Science.gov (United States)

    Song, Lijiang; Jenner, Matthew; Masschelein, Joleen; Jones, Cerith; Bull, Matthew J; Harris, Simon R; Hartkoorn, Ruben C; Vocat, Anthony; Romero-Canelon, Isolda; Coupland, Paul; Webster, Gordon; Dunn, Matthew; Weiser, Rebecca; Paisey, Christopher; Cole, Stewart T; Parkhill, Julian; Mahenthiralingam, Eshwar; Challis, Gregory L

    2017-06-14

    An antimicrobial activity screen of Burkholderia gladioli BCC0238, a clinical isolate from a cystic fibrosis patient, led to the discovery of gladiolin, a novel macrolide antibiotic with potent activity against Mycobacterium tuberculosis H37Rv. Gladiolin is structurally related to etnangien, a highly unstable antibiotic from Sorangium cellulosum that is also active against Mycobacteria. Like etnangien, gladiolin was found to inhibit RNA polymerase, a validated drug target in M. tuberculosis. However, gladiolin lacks the highly labile hexaene moiety of etnangien and was thus found to possess significantly increased chemical stability. Moreover, gladiolin displayed low mammalian cytotoxicity and good activity against several M. tuberculosis clinical isolates, including four that are resistant to isoniazid and one that is resistant to both isoniazid and rifampicin. Overall, these data suggest that gladiolin may represent a useful starting point for the development of novel drugs to tackle multidrug-resistant tuberculosis. The B. gladioli BCC0238 genome was sequenced using Single Molecule Real Time (SMRT) technology. This resulted in four contiguous sequences: two large circular chromosomes and two smaller putative plasmids. Analysis of the chromosome sequences identified 49 putative specialized metabolite biosynthetic gene clusters. One such gene cluster, located on the smaller of the two chromosomes, encodes a trans-acyltransferase (trans-AT) polyketide synthase (PKS) multienzyme that was hypothesized to assemble gladiolin. Insertional inactivation of a gene in this cluster encoding one of the PKS subunits abrogated gladiolin production, confirming that the gene cluster is responsible for biosynthesis of the antibiotic. Comparison of the PKSs responsible for the assembly of gladiolin and etnangien showed that they possess a remarkably similar architecture, obfuscating the biosynthetic mechanisms responsible for most of the structural differences between the two

  16. Preventing Ototoxic Synergy of Prior Noise Trauma During Aminoglycoside Therapy

    Science.gov (United States)

    2015-12-01

    Johns Hopkins University. 212 p (2007). 9. Liao S, et al. Noise Exposure in the Neonatal Intensive Care Unit : A Prospective Study. American Academy...AD_________________ Award Number: W81XWH-14-1-0006 TITLE: Preventing Ototoxic Synergy Of Prior Noise Trauma During Aminoglycoside Therapy ...Dec 2014 - 30 Nov 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Preventing Ototoxic Synergy Of Prior Noise Trauma During Aminoglycoside Therapy

  17. Potential chemopreventive activity of a new macrolide antibiotic from a marine-derived Micromonospora sp.

    Science.gov (United States)

    Carlson, Skylar; Marler, Laura; Nam, Sang-Jip; Santarsiero, Bernard D; Pezzuto, John M; Murphy, Brian T

    2013-04-03

    Agents capable of inducing phase II enzymes such as quinone reductase 1 (QR1) are known to have the potential of mediating cancer chemopreventive activity. As part of a program to discover novel phase II enzyme-inducing molecules, we identified a marine-derived actinomycete strain (CNJ-878) that exhibited activity with cultured Hepa 1c1c7 cells. Based on this activity, a new macrolide, juvenimicin C (1), as well as 5-O-α-L-rhamnosyltylactone (2), were isolated from the culture broth of a Micromonospora sp. Compound 1 enhanced QR1 enzyme activity and glutathione levels by two-fold with CD values of 10.1 and 27.7 μM, respectively. In addition, glutathione reductase and glutathione peroxidase activities were elevated. This is the first reported member of the macrolide class of antibiotics found to mediate these responses.

  18. Sublethal Triclosan Exposure Decreases Susceptibility to Gentamicin and Other Aminoglycosides in Listeria monocytogenes▿

    Science.gov (United States)

    Christensen, Ellen G.; Gram, Lone; Kastbjerg, Vicky G.

    2011-01-01

    The human food-borne pathogen Listeria monocytogenes is capable of persisting in food processing plants despite cleaning and sanitation and is likely exposed to sublethal biocide concentrations. This could potentially affect susceptibility of the bacterium to biocides and other antimicrobial agents. The purpose of the present study was to determine if sublethal biocide concentrations affected antibiotic susceptibility in L. monocytogenes. Exposure of L. monocytogenes strains EGD and N53-1 to sublethal concentrations of Incimaxx DES (containing peroxy acids and hydrogen peroxide) and Triquart Super (containing quaternary ammonium compound) in four consecutive cultures did not alter the frequency of antibiotic-tolerant isolates, as determined by plating on 2× the MIC for a range of antibiotics. Exposure of eight strains of L. monocytogenes to 1 and 4 μg/ml triclosan did not alter triclosan sensitivity. However, all eight strains became resistant to gentamicin (up to 16-fold increase in MIC) after exposure to sublethal triclosan concentrations. Gentamicin-resistant isolates of strains N53-1 and 4446 were also resistant to other aminoglycosides, such as kanamycin, streptomycin, and tobramycin. Gentamicin resistance remained at a high level also after five subcultures without triclosan or gentamicin. Aminoglycoside resistance can be caused by mutations in the target site, the 16S rRNA gene. However, such mutations were not detected in the N53-1-resistant isolates. A combination of gentamicin and ampicillin is commonly used in listeriosis treatment. The triclosan-induced resistance is, hence, of great concern. Further investigations are needed to determine the molecular mechanisms underlying the effect of triclosan. PMID:21746948

  19. Antibiotic Adjuvants: Rescuing Antibiotics from Resistance.

    Science.gov (United States)

    Wright, Gerard D

    2016-11-01

    Rooted in the mechanism of action of antibiotics and subject to bacterial evolution, antibiotic resistance is difficult and perhaps impossible to overcome. Nevertheless, strategies can be used to minimize the emergence and impact of resistance. Antibiotic adjuvants offer one such approach. These are compounds that have little or no antibiotic activity themselves but act to block resistance or otherwise enhance antibiotic action. Antibiotic adjuvants are therefore delivered in combination with antibiotics and can be divided into two groups: Class I agents that act on the pathogen, and Class II agents that act on the host. Adjuvants offer a means to both suppress the emergence of resistance and rescue the activity of existing drugs, offering an orthogonal strategy complimentary to new antibiotic discovery VIDEO ABSTRACT. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Chemical composition and antibacterial activities of Illicium verum against antibiotic-resistant pathogens.

    Science.gov (United States)

    Yang, Jyh-Ferng; Yang, Cheng-Hong; Chang, Hsueh-Wei; Yang, Cheng-San; Wang, Shao-Ming; Hsieh, Ming-Che; Chuang, Li-Yeh

    2010-10-01

    In recent years, human pathogenic microorganisms have developed multiple drug resistance and caused serious nosocomial infections. In this study, we identified four new antimicrobial compounds from the Chinese herbal medicine Illicium verum and assessed their antibacterial efficacies. The supercritical CO₂ and ethanol extracts of Illicium verum showed substantial antibacterial activity against 67 clinical drug-resistant isolates, including 27 Acinetobacter baumannii, 20 Pseudomonas aeruginosa, and 20 methicillin-resistant Staphylococcus aureus. The diethyl ether (EE) fraction obtained from partition extraction and supercritical CO₂ extracts revealed an antibacterial activity with a minimum inhibitory concentration value of 0.15-0.70 mg/mL and 0.11 mg/mL, respectively. The EE fraction of I. verum showed synergetic effects with some commercial antibiotics. The antimicrobial mechanism was investigated with killing curves and scanning electron microscopy observation. The chemical components of the extracts were analyzed by spectrophotometry; (E)-anethole, anisyl acetone, anisyl alcohol, and anisyl aldehyde exhibited antibacterial activity against different clinical isolates. These extracts from I. verum can be further developed into antibiotic medicines due to their proven antibacterial activity.

  1. Heat treatment effects on the antimicrobial activity of macrolide and lincosamide antibiotics in milk.

    Science.gov (United States)

    Zorraquino, M A; Althaus, R L; Roca, M; Molina, M P

    2011-02-01

    Antibiotic residues in milk can cause serious problems for consumers and the dairy industry. Heat treatment of milk may diminish the antimicrobial activity of these antibiotic residues. This study analyzed the effect of milk processing (60 °C for 30 min, 120 °C for 20 min, and 140 °C for 10 s) on the antimicrobial activity of milk samples fortified with three concentrations of three macrolides (erythromycin: 20, 40 and 80 μg/liter; spiramycin: 100, 200, and 400 μg/liter; and tylosin: 500, 1,000, and 2,000 μg/liter) and one lincosamide (lincomycin: 1,000, 2,000, and 4,000 μg/liter). To measure the loss of antimicrobial activity, a bioassay based on the growth inhibition of Micrococcus luteus was done. The data were analyzed using a multiple linear regression model. The results indicate that treatment at 120 °C for 20 min produces inactivation percentages of 93% (erythromycin), 64% (spiramycin), 51% (tylosin), and 5% (lincomycin), while treatment at 140 °C for 10 s results in generally lower percentages (30% erythromycin, 35% spiramycin, 12% tylosin, and 5% lincomycin). The lowest loss or lowest reduction of antimicrobial activity (21% erythromycin and 13% spiramycin) was obtained by treatment at 60 °C for 30 min. Copyright ©, International Association for Food Protection

  2. Quantitative structure-activity relationship analysis to elucidate the clearance mechanisms of Tc-99m labeled quinolone antibiotics

    International Nuclear Information System (INIS)

    Salahinejad, M.; Mirshojaei, S.F.

    2016-01-01

    This study aims to establish molecular modeling methods for predicting the liver and kidney uptakes of Tc-99m labeled quinolone antibiotics. Some three-dimensional quantitative-activity relationships (3D-QSAR) models were developed using comparative molecular field analysis and grid-independent descriptors procedures. As a first report on 3D-QSAR modeling, the predicted liver and kidney uptakes for quinolone antibiotics were in good agreement with the experimental values. The obtained results confirm the importance of hydrophobic interactions, size and steric hindrance of antibiotic molecules in their liver uptakes, while the electrostatic interactions and hydrogen bonding ability have impressive effects on their kidney uptakes. (author)

  3. Inhibitory Activity of Synthetic Peptide Antibiotics on Feline Immunodeficiency Virus Infectivity In Vitro

    Science.gov (United States)

    Ma, Jia; Kennedy-Stoskopf, Suzanne; Jaynes, Jesse M.; Thurmond, Linda M.; Tompkins, Wayne A.

    2002-01-01

    Natural peptide antibiotics are part of host innate immunity against a wide range of microbes, including some viruses. Synthetic peptides modeled after natural peptide antibiotics interfere with microbial membranes and are termed peptidyl membrane-interactive molecules (peptidyl-MIM [Demegen Inc, Pittsburgh, Pa.]). Sixteen peptidyl-MIM candidates were tested for activity against feline immunodeficiency virus (FIV) on infected CrFK cells. Three of them (D4E1, DC1, and D1D6) showed potent anti-FIV activity in chronically infected CrFK cells as measured by decreased reverse transcriptase (RT) activity, having 50% inhibitory concentrations of 0.46, 0.75, and 0.94 μM, respectively, which were approximately 10 times lower than their direct cytotoxic concentrations. Treatment of chronically infected CrFK cells with 2 μM D4E1 for 3 days completely reversed virus-induced cytopathic effect. Immunofluorescence revealed reduced p26 staining in these cells. Treatment of chronically infected CrFK cells with 2 μM D4E1 suppressed virus production (∼50%) for up to 7 days, The virions from the D4E1-treated culture had impaired infectivity, as measured by the 50% tissue culture infectious dose and nested PCR analysis of proviral DNA. However, these noninfectious virions were able to bind and internalize, suggesting a defect at some postentry step. After chronically infected CrFK cells were treated with D4E1 for 24 h, increased cell-associated mature p26 Gag and decreased extracellular virus-associated p26 Gag were observed by Western blot analysis, suggesting that virus assembly and/or release may be blocked by D4E1 treatment, whereas virus binding, penetration, RNA synthesis, and protein synthesis appear to be unaffected. Synthetic peptide antibiotics may be useful tools in the search for antiviral drugs having a wide therapeutic window for host cells. PMID:12208971

  4. Inhibition of lipase activity in antibiotic-resistant propionibacterium acnes strains.

    Science.gov (United States)

    Gloor, M; Wasik, B; Becker, A; Höffler, U

    2002-01-01

    Erythromycin-sensitive and/or clindamycin-sensitive strains of Propionibacterium acnes show a reduced lipase production at levels below the minimal growth-inhibitory concentration (MIC). The objective of this study was to determine whether erythromycin and clindamycin concentrations far below the MIC inhibit lipase production in P. acnes strains resistant to these antibiotics. Of 42 P. acnes strains, 10 showed an MIC >256 micro g/ml for erythromycin. Two strains showed MICs of 0.19 and 0.25 micro g/ml, while the MIC of the remaining strains was Lipase activity was determined up to a concentration of 192 micro g/ml by cultivation on spirit blue agar + lipase reagent. The 10 strains whose erythromycin MIC was >256 micro g/ml were also tested for lipase inhibition by clindamycin. While this method fails to differentiate between inhibition of lipase production and inhibition of lipase activity, the absence of inhibition of lipase activity rules out inhibition of lipase production. Inhibition of lipolysis by sub-MIC concentrations was demonstrated only for clindamycin in 3 P. acnes strains. However, lipase inhibition was seen only at the dilution level immediately below the MIC. Resistant P. acnes strains with high erythromycin and/or clindamycin MICs can be ruled out to show in vitro inhibition of lipase production at antibiotic concentrations far below the MIC. Copyright 2002 S. Karger AG, Basel

  5. Antimicrobial activity of nisin against the swine pathogen Streptococcus suis and its synergistic interaction with antibiotics.

    Science.gov (United States)

    Lebel, Geneviève; Piché, Fanny; Frenette, Michel; Gottschalk, Marcelo; Grenier, Daniel

    2013-12-01

    Streptococcus suis serotype 2 is known to cause severe infections in pigs, including meningitis, endocarditis and pneumonia. Furthermore, this bacterium is considered an emerging zoonotic agent. Recently, increased antibiotic resistance in S. suis has been reported worldwide. The objective of this study was to evaluate the potential of nisin, a bacteriocin of the lantibiotic class, as an antibacterial agent against the pathogen S. suis serotype 2. In addition, the synergistic activity of nisin in combination with conventional antibiotics was assessed. Using a plate assay, the nisin-producing strain Lactococcus lactis ATCC 11454 proved to be capable of inhibiting the growth of S. suis (n=18) belonging to either sequence type (ST)1, ST25, or ST28. In a microdilution broth assay, the minimum inhibitory concentration (MIC) of purified nisin ranged between 1.25 and 5 μg/mL while the minimum bactericidal concentration (MBC) was between 5 and 10 μg/mL toward S. suis. The use of a capsule-deficient mutant of S. suis indicated that the presence of this polysaccharidic structure has no marked impact on susceptibility to nisin. Following treatment of S. suis with nisin, transmission electron microscopy observations revealed lysis of bacteria resulting from breakdown of the cell membrane. A time-killing curve showed a rapid bactericidal activity of nisin. Lastly, synergistic effects of nisin were observed in combination with several antibiotics, including penicillin, amoxicillin, tetracycline, streptomycin and ceftiofur. This study brought clear evidence supporting the potential of nisin for the prevention and treatment of S. suis infections in pigs. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Molecular detection of aminoglycoside-modifying enzyme genes in Acinetobacter baumannii clinical isolates.

    Science.gov (United States)

    Heidary, Mohsen; Salimi Chirani, Alireza; Khoshnood, Saeed; Eslami, Gita; Atyabi, Seyyed Mohammad; Nazem, Habibollah; Fazilati, Mohammad; Hashemi, Ali; Soleimani, Saleh

    2017-06-01

    Acinetobacter baumannii is a major opportunistic pathogen in healthcare settings worldwide. In Iran, there are only few reports on the prevalence of aminoglycoside resistance genes among A. baumannii isolates. The aim of this study was to investigate the existence of aminoglycoside-modifying enzyme (AME) genes from A. baumannii strains collected at a university teaching hospital in Iran. One hundred A. baumannii strains were collected between 2014 and 2015 from hospitalized patients at Loghman Hakim Hospital, Tehran, Iran. Antimicrobial susceptibility was determined by disk diffusion method according to the Clinical and Laboratory Standards Institute recommendations. The DNA was extracted using a kit obtained from Bioneer Co. (Korea) and was used as a template for polymerase chain reaction. The most active antimicrobial agent against these strains was colistin. The rate of extended-spectrum cephalosporin resistance was 97%. The aadA1, aadB, aac(6')-Ib, and aac(3)-IIa genes were found in 85%, 77%, 72%, and 68% of A. baumannii isolates, respectively. This study showed a high prevalence rate of AME genes in A. baumannii. This prevalence rate has explained that further aminoglycoside resistance genes may have role in the resistance of clinical isolates of A. baumannii. Therefore, control and treatment of serious infections caused by this opportunistic pathogen should be given more consideration.

  7. Chemical composition and antibacterial activity of Lavandula coronopifolia essential oil against antibiotic-resistant bacteria.

    Science.gov (United States)

    Ait Said, L; Zahlane, K; Ghalbane, I; El Messoussi, S; Romane, A; Cavaleiro, C; Salgueiro, L

    2015-01-01

    The aim of this study was to analyse the composition of the essential oil (EO) of Lavandula coronopifolia from Morocco and to evaluate its in vitro antibacterial activity against antibiotic-resistant bacteria isolated from clinical infections. The antimicrobial activity was assessed by a broth micro-well dilution method using multiresistant clinical isolates of 11 pathogenic bacteria: Klebsiella pneumoniae subsp. pneumoniae, Klebsiella ornithinolytica, Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Providencia rettgeri, Citrobacter freundii, Hafnia alvei, Salmonella spp., Acinetobacter baumannii and methicillin-resistant Staphylococcus aureus. The main compounds of the oil were carvacrol (48.9%), E-caryophyllene (10.8%) and caryophyllene oxide (7.7%). The oil showed activity against all tested strains with minimal inhibitory concentration (MIC) values ranging between 1% and 4%. For most of the strains, the MIC value was equivalent to the minimal bactericidal concentration value, indicating a clear bactericidal effect of L. coronopifolia EO.

  8. Antibiotic activity and synergistic effect of antimicrobial peptide against pathogens from a patient with gallstones

    International Nuclear Information System (INIS)

    Park, Yoonkyung; Park, Soon Nang; Park, Seong-Cheol; Park, Joon Yong; Park, Yong Ha; Hahm, Joon Soo; Hahm, Kyung-Soo

    2004-01-01

    HP (2-20) is a peptide derived from the N-terminus of Helicobacter pylori ribosomal protein L1 that has been shown to have antimicrobial activity against various species of bacteria. When we tested the effects of HP (2-20), we found that this peptide displayed strong activity against pathogens from a patient with gallstones, but it did not have hemolytic activity against human erythrocytes. We also found that HP (2-20) had potent activity against cefazolin sodium-resistant bacterial cell lines, and that HP (2-20) and cefazolin sodium had synergistic effects against cell lines resistant to the latter. To investigate the mechanism of action of HP (2-20), we performed fluorescence activated flow cytometry using pathogens from the patient with gallstones. As determined by propidium iodide (PI) staining, pathogenic bacteria treated with HP (2-20) showed higher fluorescence intensity than untreated cells, similar to melittin-treated cells, and that HP (2-20) acted in an energy- and salt-dependent manner. Scanning electron microscopy showed that HP (2-20) caused significant morphological alterations in the cell surface of pathogens from the patient with gallstones. By determining their 16S rDNA sequences, we found that both the pathogens from the patient with gallstones and the cefazolin sodium-resistant cell lines showed 100% homology with sequences from Pseudomonas aeruginosa. Taken together, these results suggest that HP (2-20) has antibiotic activity and that it may be used as a lead drug for the treatment of acquired pathogens from patients with gallstones and antibiotic-resistant cell lines

  9. Biosynthetically Guided Structure-Activity Relationship Studies of Merochlorin A, an Antibiotic Marine Natural Product.

    Science.gov (United States)

    López-Pérez, Borja; Pepper, Henry P; Ma, Rong; Fawcett, Benjamin J; Pehere, Ashok D; Wei, Qi; Ji, Zengchun; Polyak, Steven W; Dai, Huanqin; Song, Fuhang; Abell, Andrew D; Zhang, Lixin; George, Jonathan H

    2017-12-07

    The onset of new multidrug-resistant strains of bacteria demands continuous development of antibacterial agents with new chemical scaffolds and mechanisms of action. We present the first structure-activity relationship (SAR) study of 16 derivatives of a structurally novel antibiotic merochlorin A that were designed using a biosynthetic blueprint. Our lead compounds are active against several Gram-positive bacteria such as Staphylococcus aureus (SA), methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE) and Bacillus subtilis, inhibit intracellular growth of Mycobacterium bovis, and are relatively nontoxic to human cell lines. Furthermore, derivative 12 c {(±)-(3aR,4S,5R,10bS)-5-bromo-7,9-dimethoxy-4-methyl-4-(4-methylpent-3-en-1-yl)-2-(propan-2-ylidene)-1,2,3,3a,4,5-hexahydro-6H-5,10b-methanobenzo[e]azulene-6,11-dione} was found to inhibit the growth of Bacillus Calmette-Guérin (BCG)-infected cells at concentrations similar to rifampicin. These results outperform the natural product, underscoring the potential of merochlorin analogues as a new class of antibiotics. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. PdtaS Deficiency Affects Resistance of Mycobacteria to Ribosome Targeting Antibiotics

    Directory of Open Access Journals (Sweden)

    Karolina Dadura

    2017-11-01

    Full Text Available Two-component regulatory systems (TCSSs are key regulatory elements responsible for the adaptation of bacteria to environmental stresses. A classical TCSS is typically comprised of a sensory histidine kinase and a corresponding response regulator. Here, we used homologous recombination to construct a Mycobacterium smegmatis mutant defective in the synthesis of cytosolic histidine kinase PdtaS (Msmeg_1918. The resulting ΔpdtaS mutant strain was tested in the Phenotype Microarray screening system, which allowed us to identify aminoglycoside antibiotic sensitivity, tetracyclines antibiotic resistance as well as membrane transport and respiration, as the main processes affected by removal of pdtaS. The antibiotic sensitivity profiles were confirmed by survival assessment and complementation studies. To gain insight into the molecular mechanisms responsible for the observed phenotype, we compared ribosomal RNA and protein profiles of the mutant and wild-type strains. We carried out Northern blotting and qRT-PCR to compare rRNA levels and analyzed ribosome sedimentation patterns of the wild-type and mutant strains on sucrose gradients. Isolated ribosomes were further used to estimate relative abundance of individual proteins in the ribosomal subunits using label free mass spectrometry analysis. Additionally, the ΔpdtaS mutant revealed lower activity of the respiratory chain as measured by the rate of TTC (triphenyltetrazolium chloride reduction, while at the same time showing only insignificant changes in the uptake of aminoglycosides. We postulate that deficiency of PdtaS affects the oxidative respiration rates and ribosomal composition causing relevant changes to intrinsic resistance or susceptibility to antibiotics targeting ribosomes, which are commonly used to treat mycobacterial infections.

  11. Antibiotic activity against naive and induced Streptococcus pneumoniae biofilms in an in vitro pharmacodynamic model.

    Science.gov (United States)

    Vandevelde, Nathalie M; Tulkens, Paul M; Van Bambeke, Françoise

    2014-01-01

    Biofilms play a role in the pathogenicity of pneumococcal infections. A pharmacodynamic in vitro model of biofilm was developed that allows characterization of the activity of antibiotics against viability and biomass by using in parallel capsulated (ATCC 49619) and noncapsulated (R6) reference strains. Naive biofilms were obtained by incubating fresh planktonic cultures for 2 to 11 days in 96-well polystyrene plates. Induced biofilms were obtained using planktonic bacteria collected from the supernatant of 6-day-old naive biofilms. Biomass production was more rapid and intense in the induced model, but the levels were similar for both strains. Full concentration responses fitting sigmoidal regressions allowed calculation of maximal efficacies and relative potencies of drugs. All antibiotics tested (amoxicillin, clarithromycin, solithromycin, levofloxacin, and moxifloxacin) were more effective against young naive biofilms than against old or induced biofilms, except macrolides/ketolides, which were as effective at reducing viability in 2-day-old naive biofilms and in 11-day-old induced biofilms of R6. Macrolides/ketolides, however, were less potent than fluoroquinolones against R6 (approximately 5- to 20-fold-higher concentrations needed to reduction viability of 20%). However, at concentrations obtainable in epithelial lining fluid, the viabilities of mature or induced biofilms were reduced 15 to 45% (amoxicillin), 17 to 44% (macrolides/ketolides), and 12 to 64% (fluoroquinolones), and biomasses were reduced 5 to 45% (amoxicillin), 5 to 60% (macrolides/ketolides), and 10 to 76% (fluoroquinolones), with solithromycin and moxifloxacin being the most effective and the most potent agents (due to lower MICs) in their respective classes. This study allowed the ranking of antibiotics with respect to their potential effectiveness in biofilm-related infections, underlining the need to search for still more effective options.

  12. Enhancement of antibiotic activity by efflux inhibitors against multidrug resistant Mycobacterium tuberculosis clinical isolates from Brazil

    Directory of Open Access Journals (Sweden)

    Tatiane eCoelho

    2015-04-01

    Full Text Available Drug resistant tuberculosis continues to increase and new approaches for its treatment are necessary. The identification of M. tuberculosis clinical isolates presenting efflux as part of their resistant phenotype has a major impact in tuberculosis treatment. In this work, we used a checkerboard procedure combined with the tetrazolium microplate-based assay (TEMA to study single combinations between antituberculosis drugs and efflux inhibitors (EIs against multidrug resistant M. tuberculosis clinical isolates using the fully susceptible strain H37Rv as reference. Efflux activity was studied on a real-time basis by a fluorometric method that uses ethidium bromide as efflux substrate. Quantification of efflux pump genes mRNA transcriptional levels were performed by RT-qPCR. The fractional inhibitory concentrations (FIC indicated synergistic activity for the interactions between isoniazid, rifampicin, amikacin, ofloxacin, and ethidium bromide plus the EIs verapamil, thioridazine and chlorpromazine. The FICs ranged from 0.25, indicating a four-fold reduction on the MICs, to 0.015, 64-fold reduction. The detection of active efflux by real-time fluorometry showed that all strains presented intrinsic efflux activity that contributes to the overall resistance which can be inhibited in the presence of the EIs. The quantification of the mRNA levels of the most important efflux pump genes on these strains shows that they are intrinsically predisposed to expel toxic compounds as the exposure to subinhibitory concentrations of antibiotics were not necessary to increase the pump mRNA levels when compared with the non-exposed counterpart. The results obtained in this study confirm that the intrinsic efflux activity contributes to the overall resistance in multidrug resistant clinical isolates of M. tuberculosis and that the inhibition of efflux pumps by the EIs can enhance the clinical effect of antibiotics that are their substrates.

  13. Distribution of genes encoding aminoglycoside-modifying enzymes among clinical isolates of methicillin-resistant staphylococci.

    Science.gov (United States)

    Perumal, N; Murugesan, S; Krishnan, P

    2016-01-01

    The objective of this study was to determine the distribution of genes encoding aminoglycoside-modifying enzymes (AMEs) and staphylococcal cassette chromosome mec (SCCmec) elements among clinical isolates of methicillin-resistant staphylococci (MRS). Antibiotic susceptibility test was done using Kirby-Bauer disk diffusion method. The presence of SCCmec types and AME genes, namely, aac (6')-Ie-aph (2''), aph (3')-IIIa and ant (4')-Ia was determined using two different multiplex polymerase chain reaction. The most encountered AME genes were aac (6')-Ie-aph (2'') (55.4%) followed by aph (3')-IIIa (32.3%) and ant (4')-Ia gene (9%). SCCmec type I (34%) was predominant in this study. In conclusion, the aac (6')-Ie-aph (2'') was the most common AME gene and SCCmec type I was most predominant among the MRS isolates.

  14. Ocimum basilicum: Antibacterial activity and association study with antibiotics against bacteria of clinical importance.

    Science.gov (United States)

    Araújo Silva, Viviane; Pereira da Sousa, Janiere; de Luna Freire Pessôa, Hilzeth; Fernanda Ramos de Freitas, Andrea; Douglas Melo Coutinho, Henrique; Beuttenmuller Nogueira Alves, Larissa; Oliveira Lima, Edeltrudes

    2016-01-01

    Ocimum basilicum L. (Lamiaceae), popularly known as basil, is part of a group of medicinal plants widely used in cooking and known for its beneficial health properties, possessing significant antioxidant effects, antinociceptive, and others. The objective of this study is to determine the pharmacological effects produced on the bacterial strains Staphylococcus aureus and Pseudomonas aeruginosa when standard antibiotics and O. basilicum essential oil are combined. The extraction of O. basilicum (leaves) components was done by steam distillation. The Minimum inhibitory concentration (MIC) was calculated using microdilution technique, where the oil concentrations varied from 2 to 1024 μg/mL. The combinations of O. basilicum oil with ciprofloxacin or imipenem were analyzed by the checkerboard method where fractional inhibitory concentration (FIC) indices were calculated. Ocimum basilicum essential oil, imipenem, and ciprofloxacin showed respective MIC antibacterial activities of 1024, 4, and 2 μg/mL, against S. aureus. In S. aureus, the oil with imipenem association showed synergistic effect (FIC = 0.0625), while the oil with ciprofloxacin showed antagonism (FIC value = 4.25). In P. aeruginosa, the imipenem/oil association showed additive effect for ATCC strains, and synergism for the clinical strain (FIC values = 0.75 and 0.0625). The association of O. basilicum essential oil with ciprofloxacin showed synergism for clinical strains (FIC value = 0.09). Ocimum basilicum essential oil associated with existing standard antibiotics may increase their antibacterial activity, resulting in a synergistic activity against bacterial strains of clinical importance. The antibacterial activity of O. basilicum essential oil may be associated with linalool.

  15. Removal of antibiotic sulfamethoxazole by anoxic/anaerobic/oxic granular and suspended activated sludge processes.

    Science.gov (United States)

    Kang, Abbass Jafari; Brown, Alistair K; Wong, Charles S; Yuan, Qiuyan

    2018-03-01

    This study investigates the removal of the antibiotic sulfamethoxazole (SMX) in two sets of anoxic/anaerobic/oxic sequencing batch reactors inoculated with either suspended or granular activated sludge. Continuously, for three months, 2 μg/L SMX was spiked into the reactor feeds in a synthetic municipal wastewater with COD, total nitrogen (TN) and total phosphorous (TP) of 400, 43 and 7 mg/L, respectively. The presence of SMX had no significant impact on treatment performance of the suspended and granular biomass. After 12 h of hydraulic retention time, SMX removal efficiencies of 84 and 73% were obtained for the granular and suspended biomass, respectively. Mixing without aeration did not remove SMX, confirming the insignificance of SMX removal via sorption. The pseudo-first order SMX removal rate constants in the granular and suspended biomass were 2.25 ± 0.30 and 1.34 ± 0.39 L/gVSS·d, respectively. The results suggest that granules with advantages such as elevated biomass retention and greater biomass concentration could be effective for the removal of this class of antibiotics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Novel purification method and antibiotic activity of recombinant Momordica charantia MAP30.

    Science.gov (United States)

    Chang, Ching-Dong; Lin, Ping-Yuan; Chen, Yo-Chia; Huang, Han-Hsiang; Shih, Wen-Ling

    2017-05-01

    Ribosome-inactivating proteins (RIPs) are a group of enzymes originally isolated from plants that possess the ability to damage ribosomes in an irreversible manner, leading to inhibition of protein synthesis in eukaryotic cells. In this study, we aimed to purify recombinant RIPs, investigate their function in the treatment of bacterial infection, and determine their toxicity in mice. We employed a pMAL protein fusion and purification system using E. coli transformed with a plasmid containing MBP-tagged MAP30 cDNA. MBP-tagged MAP30 was purified using a modified novel protocol to effectively produce highly active MAP30 of high purity. In an acute toxicity study in mice, no mortality occurred at doses lower than 1.25 mg/kg. MAP30 at both 0.42 and 0.14 mg/kg induced anti-MAP30 IgG, which reached a maximum titer at week 3. In conclusion, recombinant MAP30 prepared using our purification method possesses bioactivity, and has a synergistic bacteria-killing effect that can significantly reduce the required dosages of chloramphenicol and erythromycin. Therefore, when MAP30 is used in combination with chloramphenicol or erythromycin, it may of benefit in terms of reducing the side effects of the antibiotics, as lower concentrations of antibiotics are required.

  17. Evaluation of the Antimicrobial Activity of Silver Nanoparticles on Antibiotic-Resistant Pseudomonas aeruginosa

    Directory of Open Access Journals (Sweden)

    Aliakbar Nasiri

    2016-06-01

    Full Text Available Background: Antimicrobial resistance is one of the major characteristics of infectious agents. Silver nanoparticles (AgNPs have been introduced as novel antibacterial agents in accordance with the traditional treatments. Our purpose of this study was to evaluate the antimicrobial activity of AgNPs on the Pseudomonas aeruginosa (P. aeruginosa that are resistant to antibiotics. Methods: During a cross-sectional study, we tried to evaluate 20 strains of P. aeruginosa isolated from the urine cultures of patients admitted to the hospital due to urinary tract infections. The AgNPs were commercially purchased. The minimum inhibitory concentration (MIC of AgNPs in different concentrations was determined by the dilution in wells on bacteria. The antibiotic susceptibility pattern of P. aeruginosa was evaluated by the Kirby-Bauer disk diffusion standard. Results: Current study indicated that P. aeruginosa were resistant to four types of agents including ampicillin (85%, nitrofurantoin (65%, nalidixic acid (65%, and ciprofloxacin (15% and result of nanosilver indicated that the most MIC was 100 ppm concentration, and six strains of P. aeruginosa were inhibited by it. Conclusion: Our study presented a new type of silver nanoparticle and indicated that they can be embedded in bone cement to prevent infections once synthetic conditions are tailored for such applications.

  18. Activated carbon adsorption of quinolone antibiotics in water: Performance, mechanism, and modeling.

    Science.gov (United States)

    Fu, Hao; Li, Xuebing; Wang, Jun; Lin, Pengfei; Chen, Chao; Zhang, Xiaojian; Suffet, I H Mel

    2017-06-01

    The extensive use of antibiotics has led to their presence in the aquatic environment, and introduces potential impacts on human and ecological health. The capability of powdered activated carbon (PAC) to remove six frequently used quinolone (QN) antibiotics during water treatment was evaluated to improve drinking water safety. The kinetics of QN adsorption by PAC was best described by a pseudo second-order equation, and the adsorption capacity was well described by the Freundlich isotherm equation. Isotherms measured at different pH showed that hydrophobic interaction, electrostatic interaction, and π-π dispersion force were the main mechanisms for adsorption of QNs by PAC. A pH-dependent isotherm model based on the Freundlich equation was developed to predict the adsorption capacity of QNs by PAC at different pH values. This model had excellent prediction capabilities under different laboratory scenarios. Small relative standard derivations (RSDs), i.e., 0.59%-0.92% for ciprofloxacin and 0.09%-3.89% for enrofloxacin, were observed for equilibrium concentrations above the 0.3mg/L level. The RSDs increased to 11.9% for ciprofloxacin and 32.1% for enrofloxacin at μg/L equilibrium levels, which is still acceptable. This model could be applied to predict the adsorption of other chemicals having different ionized forms. Copyright © 2016. Published by Elsevier B.V.

  19. Antibiotic susceptibility, antibacterial activity and characterisation ofEnterococcus faeciumstrains isolated from breast milk.

    Science.gov (United States)

    Kıvanç, Sertaç Argun; Kıvanç, Merih; Yiğit, Tülay

    2016-09-01

    Enterococci, which have useful biotechnological applications, produce bacteriocins, including those that exert anti-Listerial activity. The present study aimed to determine the antibiotic susceptibility patterns and antimicrobial activity of Enterococcus faecium strains isolated from human breast milk. The strains were identified using carbohydrate fermentation tests and ribotyping. Subsequently, the antibacterial activity of the isolates was investigated, and the quantities of lactic acid and hydrogen peroxide produced, and the proteolytic activity of E. faecium , were determined. In addition, biofilm formation by E. faecium strains was assessed. E. faecium strains exhibited antimicrobial activity against food-borne and clinical bacterial isolates. Furthermore, following 24 h incubation, the tested strains exhibited resistance to a pH range of 2.0-9.5 and tolerance of bile acid, lysozyme activity and phenol. Supernatants of the E. faecium TM13, TM15, TM17 and TM18 strains were shown to be effective against Listeria monocytogenes , and were also resistant to heat. Further studies are required in order to determine whether certain strains of E. faecium may be used for the development of novel antibacterial agents.

  20. Antibiotic susceptibility, antibacterial activity and characterisation of Enterococcus faecium strains isolated from breast milk

    Science.gov (United States)

    Kıvanç, Sertaç Argun; Kıvanç, Merih; Yiğit, Tülay

    2016-01-01

    Enterococci, which have useful biotechnological applications, produce bacteriocins, including those that exert anti-Listerial activity. The present study aimed to determine the antibiotic susceptibility patterns and antimicrobial activity of Enterococcus faecium strains isolated from human breast milk. The strains were identified using carbohydrate fermentation tests and ribotyping. Subsequently, the antibacterial activity of the isolates was investigated, and the quantities of lactic acid and hydrogen peroxide produced, and the proteolytic activity of E. faecium, were determined. In addition, biofilm formation by E. faecium strains was assessed. E. faecium strains exhibited antimicrobial activity against food-borne and clinical bacterial isolates. Furthermore, following 24 h incubation, the tested strains exhibited resistance to a pH range of 2.0–9.5 and tolerance of bile acid, lysozyme activity and phenol. Supernatants of the E. faecium TM13, TM15, TM17 and TM18 strains were shown to be effective against Listeria monocytogenes, and were also resistant to heat. Further studies are required in order to determine whether certain strains of E. faecium may be used for the development of novel antibacterial agents. PMID:27602088

  1. Antibiotic discovery throughout the Small World Initiative: A molecular strategy to identify biosynthetic gene clusters involved in antagonistic activity.

    Science.gov (United States)

    Davis, Elizabeth; Sloan, Tyler; Aurelius, Krista; Barbour, Angela; Bodey, Elijah; Clark, Brigette; Dennis, Celeste; Drown, Rachel; Fleming, Megan; Humbert, Allison; Glasgo, Elizabeth; Kerns, Trent; Lingro, Kelly; McMillin, MacKenzie; Meyer, Aaron; Pope, Breanna; Stalevicz, April; Steffen, Brittney; Steindl, Austin; Williams, Carolyn; Wimberley, Carmen; Zenas, Robert; Butela, Kristen; Wildschutte, Hans

    2017-06-01

    The emergence of bacterial pathogens resistant to all known antibiotics is a global health crisis. Adding to this problem is that major pharmaceutical companies have shifted away from antibiotic discovery due to low profitability. As a result, the pipeline of new antibiotics is essentially dry and many bacteria now resist the effects of most commonly used drugs. To address this global health concern, citizen science through the Small World Initiative (SWI) was formed in 2012. As part of SWI, students isolate bacteria from their local environments, characterize the strains, and assay for antibiotic production. During the 2015 fall semester at Bowling Green State University, students isolated 77 soil-derived bacteria and genetically characterized strains using the 16S rRNA gene, identified strains exhibiting antagonistic activity, and performed an expanded SWI workflow using transposon mutagenesis to identify a biosynthetic gene cluster involved in toxigenic compound production. We identified one mutant with loss of antagonistic activity and through subsequent whole-genome sequencing and linker-mediated PCR identified a 24.9 kb biosynthetic gene locus likely involved in inhibitory activity in that mutant. Further assessment against human pathogens demonstrated the inhibition of Bacillus cereus, Listeria monocytogenes, and methicillin-resistant Staphylococcus aureus in the presence of this compound, thus supporting our molecular strategy as an effective research pipeline for SWI antibiotic discovery and genetic characterization. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  2. Antimicrobial Activity of Plectasin NZ2114 in Combination with Cell Wall Targeting Antibiotics Against VanA-Type Enterococcus faecalis.

    Science.gov (United States)

    Breidenstein, Elena B M; Courvalin, Patrice; Meziane-Cherif, Djalal

    2015-08-01

    Antimicrobial peptide plectasin targeting bacterial cell wall precursor Lipid II has been reported to be active against benzylpenicillin-resistant Streptococcus pneumoniae but less potent against vancomycin-resistant enterococci than their susceptible counterparts. The aim of this work was to test plectasin NZ2114 in combination with cell wall targeting antibiotics on vancomycin-resistant Enterococcus faecalis. The activity of antibiotic combinations was evaluated against VanA-type vancomycin-resistant E. faecalis strain BM4110/pIP816-1 by disk agar-induction, double-disk assay, determination of fractional inhibitory concentration (FIC) index, and time-kill curve. The results indicated that plectasin NZ2114 was synergistic in combination with teicoplanin, moenomycin, and dalbavancin but not with vancomycin, telavancin, penicillin G, bacitracin, ramoplanin, daptomycin, and fosfomycin. To gain an insight into the synergism, we tested other cell wall antibiotic combinations. Interestingly, synergy was observed between teicoplanin or moenomycin and the majority of the antibiotics tested; however, vancomycin was only synergistic with penicillin G. Other cell wall active antibiotics such as ramoplanin, bacitracin, and fosfomycin did not synergize. It appeared that most of the synergies observed involved inhibition of the transglycosylation step in peptidoglycan synthesis. These results suggest that teicoplanin, dalbavancin, vancomycin, and telavancin, although they all bind to the C-terminal D-Ala-D-Ala of Lipid II, might act on different stages of cell wall synthesis.

  3. The fate of inhaled antibiotics after deposition in cystic fibrosis: How to get drug to the bug?

    Science.gov (United States)

    Bos, Aukje C; Passé, Kimberly M; Mouton, Johan W; Janssens, Hettie M; Tiddens, Harm A W M

    2017-01-01

    Chronic airway infections in patients with cystic fibrosis (CF) are most often treated with inhaled antibiotics of which deposition patterns have been extensively studied. However, the journey of aerosol particles does not end after deposition within the bronchial tree. To review how local conditions affect the clinical efficacy of antibiotic aerosol particles after deposition in the airways of patients with CF. Electronic databases were searched from inception to September 2015. Original studies describing the effect of CF sputum or bacterial factors on antibiotic efficacy and formulations to increase efficacy were included. 35 articles were included which mostly described in vitro studies and mainly investigated aminoglycosides. After deposition, diffusion through the mucus layer was reduced for aminoglycosides, β-lactam antibiotics and fluoroquinolones. Within CF mucus, low oxygen tension adversely affected aminoglycosides, β-lactam antibiotics, and chloramphenicol; and molecules inactivated aminoglycosides but not β-lactam antibiotics. Finally, the alginate layer surrounding Pseudomonas aeruginosa was an important factor in the resistance against all antibiotics. After deposition in the airways, the local efficacy of inhaled antibiotics can be reduced by molecules within CF mucus and the alginate layer surrounding P. aeruginosa. Copyright © 2017 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  4. Differential trypanocidal activity of novel macrolide antibiotics; correlation to genetic lineage.

    Directory of Open Access Journals (Sweden)

    Carolina Aquilino

    Full Text Available Here we report the systematic study of the anti-trypanocidal activity of some new products derived from S. diastatus on 14 different T. cruzi strains spanning the six genetic lineages of T. cruzi. As the traditional growth inhibition curves giving similar IC(50 showed great differences on antibiotic and lineage tested, we decided to preserve the wealth of information derived from each inhibition curve and used an algorithm related to potency of the drugs, combined in a matrix data set used to generate a cluster tree. The cluster thus generated based just on drug susceptibility data closely resembles the phylogenies of the lineages derived from genetic data and provides a novel approach to correlate genetic data with phenotypes related to pathogenesis of Chagas disease. Furthermore we provide clues on the drugs mechanism of action.

  5. Differential trypanocidal activity of novel macrolide antibiotics; correlation to genetic lineage.

    Science.gov (United States)

    Aquilino, Carolina; Gonzalez Rubio, Maria Luisa; Seco, Elena Maria; Escudero, Leticia; Corvo, Laura; Soto, Manuel; Fresno, Manuel; Malpartida, Francisco; Bonay, Pedro

    2012-01-01

    Here we report the systematic study of the anti-trypanocidal activity of some new products derived from S. diastatus on 14 different T. cruzi strains spanning the six genetic lineages of T. cruzi. As the traditional growth inhibition curves giving similar IC(50) showed great differences on antibiotic and lineage tested, we decided to preserve the wealth of information derived from each inhibition curve and used an algorithm related to potency of the drugs, combined in a matrix data set used to generate a cluster tree. The cluster thus generated based just on drug susceptibility data closely resembles the phylogenies of the lineages derived from genetic data and provides a novel approach to correlate genetic data with phenotypes related to pathogenesis of Chagas disease. Furthermore we provide clues on the drugs mechanism of action.

  6. Effects of loading concentration, blood and synovial fluid on antibiotic release and anti-biofilm activity of bone cement beads.

    Science.gov (United States)

    Dusane, Devendra H; Diamond, Scott M; Knecht, Cory S; Farrar, Nicholas R; Peters, Casey W; Howlin, Robert P; Swearingen, Matthew C; Calhoun, Jason H; Plaut, Roger D; Nocera, Tanya M; Granger, Jeffrey F; Stoodley, Paul

    2017-02-28

    Antibiotic loaded cement beads are commonly used for the treatment of biofilm related orthopaedic periprosthetic infections; however the effects of antibiotic loading and exposure of beads to body fluids on release kinetics are unclear. The purpose of this study was to determine the effects of (i) antibiotic loading density (ii) loading amount (iii) material type and (iv) exposure to body fluids (blood or synovial fluid) on release kinetics and efficacy of antibiotics against planktonic and lawn biofilm bacteria. Short-term release into an agar gel was evaluated using a fluorescent tracer (fluorescein) incorporated in the carrier materials calcium sulfate (CaSO 4 ) and poly methyl methacrylate (PMMA). Different fluorescein concentrations in CaSO 4 beads were evaluated. Mechanical properties of fluorescein-incorporated beads were analyzed. Efficacy of the antibiotics vancomycin (VAN) or tobramycin (TOB) alone and in combination was evaluated against lawn biofilms of bioluminescent strains of Staphylococcus aureus and Pseudomonas aeruginosa. Zones of inhibition of cultures (ZOI) were measured visually and using an in-vivo imaging system (IVIS). The influence of body fluids on release was assessed using CaSO 4 beads that contained fluorescein or antibiotics and were pre-coated with human blood or synovial fluid. The spread from the beads followed a square root of time relationship in all cases. The loading concentration had no influence on short-term fluorescein release and pre-coating of beads with body fluids did not affect short-term release or antibacterial activity. Compared to PMMA, CaSO 4 had a more rapid short term rate of elution and activity against planktonic and lawn biofilms. This study highlights the importance of considering antibiotic loading and packing density when investigating the clinical application of bone cements for infection management. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Photocatalytic Role of Zinc Oxide Nanoparticles on Synthetic Activated Carbon to Remove Antibiotic from Aquatic Environment

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Samarghandi

    2017-10-01

    Full Text Available Background & Aims of the Study: The presence of antibiotics in the environment, especially in aquatic environments is a major concern for health and the environment. The advanced oxidation process due to the ease of use, economical advantages and high performance have attracted a lot of attention. The purpose of this study was Evaluating of the photocatalytic role of zinc oxide on synthetic activated carbon to remove antibiotic from aquatic environment. Materials & Methods: This experimental study was done in batch reactor that has a 1 L volume. In this study effect of parameters such as initial pH (3-9, initial concentration of cefazolin (20-200 mg/L, modified photocatalyst concentration (20-100 mg/L and reaction time (10-60 min was investigated. In this study a low-pressure mercury lamp with the power of 55 watts in stainless case has been used. The cefazolin concentrations in different steps were measured using UV-Vis spectrophotometer in Wavelength of 262 nm. Results: The results showed that the highest removal efficiency (96% of cefazolin was at the pH=3, 0.1 mg/L of modified photocatalyst, retention time of 60 min and cefazolin concentrations of 100 mg/L. In the case of changing any of the above mentioned values, process efficiency was decreased. Conclusion: The results showed that the photocatalytic process of zinc oxide nanoparticles on synthetic activated carbon can be used as an advanced oxidation process to effectively remove pollutants like cefazolin and other similar pollutants.

  8. Domain Dissection and Characterization of the Aminoglycoside Resistance Enzyme ANT(3″)-Ii/AAC(6′)-IId from Serratia marcescens

    Science.gov (United States)

    Green, Keith D.; Garneau-Tsodikova, Sylvie

    2013-01-01

    Aminoglycosides (AGs) are broad-spectrum antibiotics whose constant use and presence in growth environment has led bacteria to develop resistance mechanisms to aid in their survival. A common mechanism of resistance to AGs is their chemical modification (nucleotidylation, phosphorylation, or acetylation) by AG-modifying enzymes (AMEs). Through evolution, fusion of two AME-encoding genes has resulted in bifunctional enzymes with broader spectrum of activity. Serratia marcescens, a human enteropathogen, contains such a bifunctional enzyme, ANT(3″)-Ii/AAC(6′)-IId. To gain insight into the role, effect, and importance of the union of ANT(3″)-Ii and AAC(6′)-IId in this bifunctional enzyme, we separated the two domains and compared their activity to that of the full-length enzyme. We performed a thorough comparison of the substrate and cosubstrate profiles as well as kinetic characterization of the bifunctional ANT(3″)-Ii/AAC(6′)-IId and its individually expressed components. PMID:23485681

  9. Mannitol enhances antibiotic sensitivity of persister bacteria in Pseudomonas aeruginosa biofilms.

    Directory of Open Access Journals (Sweden)

    Nicolas Barraud

    Full Text Available The failure of antibiotic therapies to clear Pseudomonas aeruginosa lung infection, the key mortality factor for cystic fibrosis (CF patients, is partly attributed to the high tolerance of P. aeruginosa biofilms. Mannitol has previously been found to restore aminoglycoside sensitivity in Escherichia coli by generating a proton-motive force (PMF, suggesting a potential new strategy to improve antibiotic therapy and reduce disease progression in CF. Here, we used the commonly prescribed aminoglycoside tobramycin to select for P. aeruginosa persister cells during biofilm growth. Incubation with mannitol (10-40 mM increased tobramycin sensitivity of persister cells up to 1,000-fold. Addition of mannitol to pre-grown biofilms was able to revert the persister phenotype and improve the efficacy of tobramycin. This effect was blocked by the addition of a PMF inhibitor or in a P. aeruginosa mutant strain unable to metabolise mannitol. Addition of glucose and NaCl at high osmolarity also improved the efficacy of tobramycin although to a lesser extent compared to mannitol. Therefore, the primary effect of mannitol in reverting biofilm associated persister cells appears to be an active, physiological response, associated with a minor contribution of osmotic stress. Mannitol was tested against clinically relevant strains, showing that biofilms containing a subpopulation of persister cells are better killed in the presence of mannitol, but a clinical strain with a high resistance to tobramycin was not affected by mannitol. Overall, these results suggest that in addition to improvements in lung function by facilitating mucus clearance in CF, mannitol also affects antibiotic sensitivity in biofilms and does so through an active, physiological response.

  10. Ultrathin antibiotic walled microcapsules.

    Science.gov (United States)

    Khopade, Ajay J; Arulsudar, N; Khopade, Surekha A; Hartmann, J

    2005-01-01

    Ultrathin microcapsules comprised of anionic polyelectrolytes (PE) and a polycationic aminoglycoside (AmG) antibiotic drug were prepared by depositing PE/AmG multilayers on zinc oxide (ZnO) colloid particles using the layer-by-layer self-assembly technique and subsequently dissolving the ZnO templated cores. The polyelectrolytes, dextran sulfate sodium (DxS) and poly(styrenesulfonate) (PSS), were selected owing to their different backbone structure. An aminoglycoside, tobramycin sulfate (TbS), was used for studying DxS/TbS or PSS/TbS multilayer films. The multilayer growth on ZnO cores was characterized by alternating zeta potential values that were different for the DxS/TbS and PSS/TbS multilayers due to the PE chemistry and its interaction with Zn(2+) ions. Transmission and scanning electron microscopy provide evidence of PE/TbS multilayer coating on ZnO core particles. The slow acid-decomposition of the ZnO cores using weak organic acids and the presence of sufficient quantity of Zn(2+) in the dispersion were required to produce antibiotic multilayer capsules. There was no difference in the morphological characteristics of the two types of capsules; although, the yield for [PSS/TbS](5) capsules was significantly higher than for [DxS/TbS](5) capsules which was related to the physicochemical properties of DxS/TbS/Zn(2+) and PSS/TbS/Zn(2+) complexes forming the capsule wall. The TbS quantity in the multilayer films was determined using a quartz crystal microbalance and high performance liquid chromatography techniques which showed less TbS loading in both, capsules and multilayers on planar gold substrate, than the theoretical DxS:TbS or PSS:TbS stoichiometric ratio. The decomposition of the [PE/TbS](6) multilayers was fastest in physiological buffer followed by mannitol and water. The decomposition rate of the [PSS/TbS](6) multilayers was slower than [DxS/TbS](6) monolayers. The incomplete decomposition of DxS/TbS under saline conditions suggests the major role of

  11. Thermodynamics of aminoglycoside and acyl-coenzyme A binding to the Salmonella enterica AAC(6')-Iy aminoglycoside N-acetyltransferase.

    Science.gov (United States)

    Hegde, Subray S; Dam, Tarun K; Brewer, C Fred; Blanchard, John S

    2002-06-11

    Kinetic and mechanistic studies on the chromosomally encoded aminoglycoside 6'-N-acetyltransferase, AAC(6')-Iy, of Salmonella enterica that confers resistance toward aminoglycosides have been previously reported [Magnet et al. (2001) Biochemistry 40, 3700-3709]. In the present study, equilibrium binding and the thermodynamic parameters of binding of aminoglycosides and acyl-coenzyme A derivatives to AAC(6')-Iy and of two mutants, C109A and the C109A/C70A double mutant, have been studied using fluorescence spectroscopy and isothermal titration calorimetry (ITC). Association constants for different aminoglycosides varied greatly (4 x 10(4)-150 x 10(4)) while the association constants of several acyl-coenzyme A derivatives were similar (3.2 x 10(4)-4.5 x 10(4)). The association constants and van't Hoff enthalpy changes derived from intrinsic protein fluorescence changes were in agreement with independently measured values from isothermal titration calorimetry studies. Binding of both aminoglycosides and acyl-coenzyme A derivatives is strongly enthalpically driven and revealed opposing negative entropy changes, resulting in enthalpy-entropy compensation. The acetyltransferase exhibited a temperature-dependent binding of tobramycin with a negative heat capacity value of 410 cal mol(-1) K(-1). Isothermal titration studies of acetyl-coenzyme A and tobramycin binding to mutant forms of the enzyme indicated that completely conserved C109 does not play any direct role in the binding of either of the substrates, while C70 is directly involved in aminoglycoside binding. These results are discussed and compared with previous steady-state kinetic studies of the enzyme.

  12. Outcome measurement of extensive implementation of antimicrobial stewardship in patients receiving intravenous antibiotics in a Japanese university hospital.

    Science.gov (United States)

    Niwa, T; Shinoda, Y; Suzuki, A; Ohmori, T; Yasuda, M; Ohta, H; Fukao, A; Kitaichi, K; Matsuura, K; Sugiyama, T; Murakami, N; Itoh, Y

    2012-10-01

    Antimicrobial stewardship has not always prevailed in a wide variety of medical institutions in Japan. The infection control team was involved in the review of individual use of antibiotics in all inpatients (6348 and 6507 patients/year during the first and second annual interventions, respectively) receiving intravenous antibiotics, according to the published guidelines, consultation with physicians before prescription of antimicrobial agents and organisation of education programme on infection control for all medical staff. The outcomes of extensive implementation of antimicrobial stewardship were evaluated from the standpoint of antimicrobial use density, treatment duration, duration of hospital stay, occurrence of antimicrobial-resistant bacteria and medical expenses. Prolonged use of antibiotics over 2 weeks was significantly reduced after active implementation of antimicrobial stewardship (2.9% vs. 5.2%, p generation cephalosporins (p = 0.03), carbapenems (p = 0.003), aminoglycosides (p antibiotics by 11.7%. The appearance of methicillin-resistant Staphylococcus aureus and the proportion of Serratia marcescens to Gram-negative bacteria decreased significantly from 47.6% to 39.5% (p = 0.026) and from 3.7% to 2.0% (p = 0.026), respectively. Moreover, the mean hospital stay was shortened by 2.9 days after active implementation of antimicrobial stewardship. Extensive implementation of antimicrobial stewardship led to a decrease in the inappropriate use of antibiotics, saving in medical expenses, reduction in the development of antimicrobial resistance and shortening of hospital stay. © 2012 Blackwell Publishing Ltd.

  13. A new subclass of intrinsic aminoglycoside nucleotidyltransferases, ANT(3")-II, is horizontally transferred among Acinetobacter spp. by homologous recombination

    Science.gov (United States)

    Zhang, Gang; Leclercq, Sébastien Olivier; Tian, Jingjing; Wang, Chao; Ai, Guomin; Liu, Shuangjiang

    2017-01-01

    The emergence and spread of antibiotic resistance among Acinetobacter spp. have been investigated extensively. Most studies focused on the multiple antibiotic resistance genes located on plasmids or genomic resistance islands. On the other hand, the mechanisms controlling intrinsic resistance are still not well understood. In this study, we identified the novel subclass of aminoglycoside nucleotidyltransferase ANT(3")-II in Acinetobacter spp., which comprised numerous variants distributed among three main clades. All members of this subclass can inactivate streptomycin and spectinomycin. The three ant(3")-II genes, encoding for the three ANT(3")-II clades, are widely distributed in the genus Acinetobacter and always located in the same conserved genomic region. According to their prevalence, these genes are intrinsic in Acinetobacter baumannii, Acinetobacter pittii, and Acinetobacter gyllenbergii. We also demonstrated that the ant(3")-II genes are located in a homologous recombination hotspot and were recurrently transferred among Acinetobacter species. In conclusion, our findings demonstrated a novel mechanism of natural resistance in Acinetobacter spp., identified a novel subclass of aminoglycoside nucleotidyltransferase and provided new insight into the evolutionary history of intrinsic resistance genes. PMID:28152054

  14. The effects of active efflux pumps on antibiotic resistance in Pseudomonas aeruginosa.

    Science.gov (United States)

    Terzi, Huseyin Agah; Kulah, Canan; Ciftci, Ihsan Hakkı

    2014-10-01

    In this study, we investigated the roles of active efflux pumps in antibiotic resistance. The transcription efflux pump genes were analyzed by real-time polymerase chain reaction (qPCR) to determine their role in drug resistance. Antibiotic sensitivity testing was carried out using the Vitek 2 automated system (bioMérieux, France). Isolates were divided into four groups according to their resistance status: multiple-drug resistant (MDR), isolated carbapenem resistant (ICR), isolated quinolone resistant (IQR), and carbapenem and quinolone resistant (CQR). Transcript levels of mexB, mexD, mexF, and mexY were analyzed by qPCR using a LightCycler instrument (Roche, Germany). The genetic similarity between isolates was determined using arbitrarily primed PCR (AP-PCR). Among the 50 isolates investigated, the frequency of genes classified as overexpressed were 88 % for mexD, 76 % for mexB, 46 % for mexF, and 40 % for mexY. Within the MDR group, mexB was overexpressed in 15 of 22 isolates, mexD in 20 of 22, mexF in 15 of 22, and mexY in 19 of 22. In the ICR group, isolates mexB and mexD were each overexpressed in five isolates. mexD overexpression was observed in all seven CQR isolates. Within the IQR group, mexB and mexD were overexpressed in all 12 isolates. mexF overexpression was detected in 7 of 12 isolates in this group. 18 distinct banding patterns were determined by AP-PCR. Increased transcription of mexB was directly correlated with meropenem resistance in the majority of isolates tested, while MexCD-OprJ and MexEF-OprN were related to quinolone resistance; the MexCD-OprJ efflux pump was also related to multidrug resistance. Increased transcription of mexY may contribute to the gentamicin resistance.

  15. A facile synthesis of 1,5-disubstituted-2-aminoimidazoles: antibiotic activity of a first generation library.

    Science.gov (United States)

    Harris, Tyler L; Worthington, Roberta J; Melander, Christian

    2011-08-01

    An efficient synthetic route to 1,5-disubstituted 2-aminoimidazoles from readily available amino acids and aldehydes has been developed. A library of simple analogues was synthesized and several compounds were shown to exhibit notable antibiotic activity against a variety of bacterial strains including multi-drug resistant isolates. Copyright © 2011 Elsevier Ltd. All rights reserved.

  16. On the Enhanced Antibacterial Activity of Antibiotics Mixed with Gold Nanoparticles

    Science.gov (United States)

    Burygin, G. L.; Khlebtsov, B. N.; Shantrokha, A. N.; Dykman, L. A.; Bogatyrev, V. A.; Khlebtsov, N. G.

    2009-08-01

    The bacterial action of gentamicin and that of a mixture of gentamicin and 15-nm colloidal-gold particles on Escherichia coli K12 was examined by the agar-well-diffusion method, enumeration of colony-forming units, and turbidimetry. Addition of gentamicin to colloidal gold changed the gold color and extinction spectrum. Within the experimental errors, there were no significant differences in antibacterial activity between pure gentamicin and its mixture with gold nanoparticles (NPs). Atomic absorption spectroscopy showed that upon application of the gentamicin-particle mixture, there were no gold NPs in the zone of bacterial-growth suppression in agar. Yet, free NPs diffused into the agar. These facts are in conflict with the earlier findings indicating an enhancement of the bacterial activity of similar gentamicin-gold nanoparticle mixtures. The possible causes for these discrepancies are discussed, and the suggestion is made that a necessary condition for enhancement of antibacterial activity is the preparation of stable conjugates of NPs coated with the antibiotic molecules.

  17. On the Enhanced Antibacterial Activity of Antibiotics Mixed with Gold Nanoparticles

    Directory of Open Access Journals (Sweden)

    Shantrokha AN

    2009-01-01

    Full Text Available Abstract The bacterial action of gentamicin and that of a mixture of gentamicin and 15-nm colloidal-gold particles onEscherichia coliK12 was examined by the agar-well-diffusion method, enumeration of colony-forming units, and turbidimetry. Addition of gentamicin to colloidal gold changed the gold color and extinction spectrum. Within the experimental errors, there were no significant differences in antibacterial activity between pure gentamicin and its mixture with gold nanoparticles (NPs. Atomic absorption spectroscopy showed that upon application of the gentamicin-particle mixture, there were no gold NPs in the zone of bacterial-growth suppression in agar. Yet, free NPs diffused into the agar. These facts are in conflict with the earlier findings indicating an enhancement of the bacterial activity of similar gentamicin–gold nanoparticle mixtures. The possible causes for these discrepancies are discussed, and the suggestion is made that a necessary condition for enhancement of antibacterial activity is the preparation of stable conjugates of NPs coated with the antibiotic molecules.

  18. Spirotetronate antibiotics with anti-Clostridium activity from Actinomadura sp. 2EPS.

    Science.gov (United States)

    Euanorasetr, Jirayut; Intra, Bungonsiri; Mongkol, Phayungsak; Chankhamhaengdecha, Surang; Tuchinda, Patoomratana; Mori, Mihoko; Shiomi, Kazuro; Nihira, Takuya; Panbangred, Watanalai

    2015-02-01

    The rare actinomycetes strain 2EPS was isolated from soil and analysis of cultural, morphological characteristics, diaminopimelic acid content of its cell wall, and 16S rRNA gene sequence indicates that 2EPS belongs to genus Actinomadura. In addition, neighbor-joining phylogenetic tree also confirmed the relationships of this strain to other members of Actinomadura. A butanol extract with antibacterial activity was purified by reversed-phase chromatography to obtain three bioactive compounds, designated as compounds 1, 2 and 3. The structures of these compounds were determined using spectroscopic analysis ((1)H-NMR and (13)C-NMR) and mass spectrometric analysis (HR-TOF-MS). Compounds 1-3 were identified and found to be the same as those included in the Japanese patent number JP 09227587 for spirotetronate antibiotics and are BE-45722A (1), BE-45722B (2) and BE-45722C (3), respectively. All compounds were active against Gram-positive bacteria (Staphylococcus aureus ATCC 25923, Bacillus cereus ATCC 14579, and B. subtilis ATCC 6633) with low MIC values between 0.08 and 5.0 µg/ml. Moreover, both 1 and 3 also exhibited strong activity, with similar MIC values, against Clostridium perfringens S107 at 0.63 µg/ml and C. difficile 630 at 0.08 µg/ml. These results suggest the identified spirotetronate compounds may have potential in the treatment of Clostridium infections. Overall, this analysis demonstrates that rare actinomycetes are a promising source for discovery of antimicrobial compounds.

  19. Influence of a macrolide antibiotic, roxithromycin, on mast cell growth and activation in vitro

    Directory of Open Access Journals (Sweden)

    Toshikazu Shimane

    2001-01-01

    Full Text Available Background: Long-term administration of macrolide antibiotics is recognized to be able to favorably modify the clinical condition of inflammatory diseases, such as diffuse panbronchiolitis and cystic fibrosis. However, the precise mechanisms by which macrolide antibiotics could improve clinical conditions of the patients are not well understood.

  20. In vitro effect of aminoglycosides and fluoroquinolones on ...

    African Journals Online (AJOL)

    A viable isolate of coagulase positive and pigment forming Staphylococcus aureus obtained from conjunctival swabs used in the study was treated with aminoglycosides (gentamicin, 0.3%, and tobramycin bramycin, 0.3%, ophthalmic solution) and fluoroquinolones (gatifloxacin 0.3% and moxifloxacin, 0.3% ophthalmic ...

  1. The risks of concurrent treatment with tenofovir and aminoglycosides ...

    African Journals Online (AJOL)

    The risks of concurrent treatment with tenofovir and aminoglycosides in patients with HIV-associated tuberculosis. C Kenyon, N Wearne, R Burton, G Meintjes. Abstract. The South African public sector antiretroviral treatment (ART) guidelines have recently been changed to include tenofovir in the first-line regimen.1 ...

  2. Real-time detection of antibiotic activity by measuring nanometer-scale bacterial deformation

    Science.gov (United States)

    Iriya, Rafael; Syal, Karan; Jing, Wenwen; Mo, Manni; Yu, Hui; Haydel, Shelley E.; Wang, Shaopeng; Tao, Nongjian

    2017-12-01

    Diagnosing antibiotic-resistant bacteria currently requires sensitive detection of phenotypic changes associated with antibiotic action on bacteria. Here, we present an optical imaging-based approach to quantify bacterial membrane deformation as a phenotypic feature in real-time with a nanometer scale (˜9 nm) detection limit. Using this approach, we found two types of antibiotic-induced membrane deformations in different bacterial strains: polymyxin B induced relatively uniform spatial deformation of Escherichia coli O157:H7 cells leading to change in cellular volume and ampicillin-induced localized spatial deformation leading to the formation of bulges or protrusions on uropathogenic E. coli CFT073 cells. We anticipate that the approach will contribute to understanding of antibiotic phenotypic effects on bacteria with a potential for applications in rapid antibiotic susceptibility testing.

  3. Impact of different antibiotics on methane production using waste-activated sludge: mechanisms and microbial community dynamics.

    Science.gov (United States)

    Mustapha, Nurul Asyifah; Sakai, Kenji; Shirai, Yoshihito; Maeda, Toshinari

    2016-11-01

    Anaerobic digestion is an effective method for reducing the by-product of waste-activated sludge (WAS) from wastewater treatment plants and for producing bioenergy from WAS. However, only a limited number of studies have attempted to improve anaerobic digestion by targeting the microbial interactions in WAS. In this study, we examined whether different antibiotics positively, negatively, or neutrally influence methane fermentation by evaluating changes in the microbial community and functions in WAS. Addition of azithromycin promoted the microbial communities related to the acidogenic and acetogenic stages, and a high concentration of soluble proteins and a high activity of methanogens were detected. Chloramphenicol inhibited methane production but did not affect the bacteria that contribute to the hydrolysis, acidogenesis, and acetogenesis digestion stages. The addition of kanamycin, which exhibits the same methane productivity as a control (antibiotic-free WAS), did not affect all of the microbial communities during anaerobic digestion. This study demonstrates the simultaneous functions and interactions of diverse bacteria and methanogenic Archaea in different stages of the anaerobic digestion of WAS. The ratio of Caldilinea, Methanosarcina, and Clostridium may correspond closely to the trend of methane production in each antibiotic. The changes in microbial activities and function by antibiotics facilitate a better understanding of bioenergy production.

  4. Antibacterial activity of three newly-synthesized chalcones & synergism with antibiotics against clinical isolates of methicillin-resistant Staphylococcus aureus

    Science.gov (United States)

    Božić, Dragana D.; Milenković, Marina; Ivković, Branka; Cirković, Ivana

    2014-01-01

    Background & objectives: Multidrug-resistance of methicillin-resistant Staphylococcus aureus (MRSA) is a serious therapeutical problem. Chalcones belong to a group of naturally occurring flavonoids, usually found in various plant species, and have potent antibacterial, antiviral and antifungal activities. The goal of this study was to evaluate the antibacterial effect of three newly-synthesized chalcones against clinical isolates of MRSA, and their synergism with β-lactam and non- β-lactam antibiotics. Methods: Antimicrobial activity of the three newly-synthesized chalcones was tested against 19 clinical isolates of MRSA and a laboratory control strain of MRSA (ATCC 43300). The synergism with β-lactams: cefotaxime (CFX), ceftriaxone (CTX), and non-β-lactam antibiotics: ciprofloxacin (CIP), gentamicin (GEN) and trimethoprim/sulphamethoxazole (TMP-SMX) was investigated by checkerboard method. Results: All evaluated compounds showed significant anti-MRSA activity with MIC values from 25-200 μg/ml. Observed synergism with antibiotics demonstrated that chalcones significantly enhanced the efficacy of CIP, GEN and TMP-SMX. Interpretation & conclusions: Our study demonstrated that three newly-synthesized chalcones exhibited significant anti-MRSA effect and synergism with non-β-lactam antibiotics. The most effective compound was 1,3-Bis-(2-hydroxy-phenyl)-propenone. Our results provide useful information for future research of possible application of chalcones in combination with conventional anti-MRSA therapy as promising new antimicrobial agents. PMID:25222788

  5. In vitro activity of fluoroquinolones (gatifloxacin, levofloxacin and trovafloxacin and seven other antibiotics against Streptococcus pneumoniae

    Directory of Open Access Journals (Sweden)

    Nicodemo A.C.

    2001-01-01

    Full Text Available In recent years, the level of resistance of S. pneumoniae to beta-lactam and/or macrolides has increased around the world including some countries in South America. Because of this resistance, it is necessary to test the therapeutic alternatives for treating this pathogen, including the newer quinolones. This study was carried out in order to compare the in vitro activity of fluoroquinolones gatifloxacin, levofloxacin and trovafloxacin, to penicillin G, amoxicillin, amoxicillin-clavulanate, cufuroxime sodium, ceftriaxone, azithromycin and clarithromycin, against 300 strains of S. pneumoniae. Of the 300 samples tested, 18.6% were not susceptible to penicillin (56 strains and 7% (21 strains were resistant to the second generation cephalosporin. Among the macrolides, resistance ranged from 6.7% for clarithromycin to 29.6% for azithromycin. Susceptibility to the newer quinolones was 100% including the 56 strains not susceptible to penicillin. Among the 10 antibiotics evaluated, the fluoroquinolones gatifloxacin, levofloxacin, and trovafloxacin displayed high levels of in vitro activity against S. pneumoniae.

  6. In vitro activity of fosfomycin trometamol and other oral antibiotics against multidrug-resistant uropathogens.

    Science.gov (United States)

    Mezzatesta, Maria Lina; La Rosa, Giulia; Maugeri, Gaetano; Zingali, Tiziana; Caio, Carla; Novelli, Andrea; Stefani, Stefania

    2017-06-01

    Clinical midstream and urinary catheter isolates (n = 106) of extended-spectrum β-lactamase (ESBL)-positive Escherichia coli, Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae, Proteus mirabilis and meticillin-resistant Staphylococcus saprophyticus were tested against fosfomycin using the agar dilution method, the broth microdilution method and the gradient test described by the Clinical and Laboratory Standards Institute. Nitrofurantoin, co-trimoxazole, amoxicillin/clavulanic acid, cefuroxime, levofloxacin and ciprofloxacin were tested using the gradient test alone. Breakpoints from the European Committee on Antimicrobial Susceptibility Testing 2015 guidelines were used. Fosfomycin inhibited all of the ESBL-positive E. coli, P. mirabilis and meticillin-resistant S. saprophyticus strains isolated from urine, as well as 82% of KPC-producing K. pneumoniae isolates. Substantial agreement for fosfomycin activity was found for the three test methods, particularly for Enterobacteriaceae. This study confirmed that fosfomycin has good in vitro activity against more common multidrug-resistant uropathogens. Fosfomycin could be a reliable empirical therapeutic option for uncomplicated urinary tract infections caused by these organisms, and a valid option for sparing parenteral antibiotics, such as carbapenems. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  7. Antimicrobial activities of widely consumed herbal teas, alone or in combination with antibiotics: an in vitro study

    Directory of Open Access Journals (Sweden)

    Mayram Hacioglu

    2017-07-01

    Full Text Available Background Because of increasing antibiotic resistance, herbal teas are the most popular natural alternatives for the treatment of infectious diseases, and are currently gaining more importance. We examined the antimicrobial activities of 31 herbal teas both alone and in combination with antibiotics or antifungals against some standard and clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, methicillin susceptible/resistant Staphylococcus aureus and Candida albicans. Methods The antimicrobial activities of the teas were determined by using the disk diffusion and microbroth dilution methods, and the combination studies were examined by using the microbroth checkerboard and the time killing curve methods. Results Rosehip, rosehip bag, pomegranate blossom, thyme, wormwood, mint, echinacea bag, cinnamon, black, and green teas were active against most of the studied microorganisms. In the combination studies, we characterized all the expected effects (synergistic, additive, and antagonistic between the teas and the antimicrobials. While synergy was observed more frequently between ampicillin, ampicillin-sulbactam, or nystatine, and the various tea combinations, most of the effects between the ciprofloxacin, erythromycin, cefuroxime, or amikacin and various tea combinations, particularly rosehip, rosehip bag, and pomegranate blossom teas, were antagonistic. The results of the time kill curve analyses showed that none of the herbal teas were bactericidal in their usage concentrations; however, in combination with antibiotics they showed some bactericidal effect. Discussion Some herbal teas, particularly rosehip and pomegranate blossom should be avoided because of their antagonistic interactions with some antibiotics during the course of antibiotic treatment or they should be consumed alone for their antimicrobial activities.

  8. Increasing Prevalence of Aminoglycoside-Resistant Enterococcus faecalis Isolates Due to the aac(6')-aph(2") Gene: A Therapeutic Problem in Kermanshah, Iran.

    Science.gov (United States)

    Khani, Mitra; Fatollahzade, Mahdie; Pajavand, Hamid; Bakhtiari, Somaye; Abiri, Ramin

    2016-03-01

    Enterococci are important pathogens in nosocomial infections. Various types of antibiotics, such as aminoglycosides, are used for treatment of these infections. Enterococci can acquire resistant traits, which can lead to therapeutic problems with aminoglycosides. This study was designed to identify the prevalence of, and to compare, the aac(6')-aph(2") and aph(3)-IIIa genes and their antimicrobial resistance patterns among Enterococcus faecalis and E. faecium isolates from patients at Imam Reza hospital in Kermanshah in 2011 - 2012. One hundred thirty-eight clinical specimens collected from different wards of Imam Reza hospital were identified to the species level by biochemical tests. Antimicrobial susceptibility tests against kanamycin, teicoplanin, streptomycin, imipenem, ciprofloxacin, and ampicillin were performed by the disk diffusion method. The minimum inhibitory concentrations of gentamicin, streptomycin, kanamycin, and amikacin were evaluated with the microbroth dilution method. The aminoglycoside resistance genes aac(6')-aph(2") and aph(3")-IIIa were analyzed with multiplex PCR. The prevalence of isolates was 33 (24.1%) for E. faecium and 63 (46%) for E. faecalis. Eighty-nine percent of the isolates were high-level gentamicin resistant (HLGR), and 32.8% of E. faecium isolates and 67.2% of E. faecalis isolates carried aac(6')-aph(2"). The prevalence of aph(3")-IIIa among the E. faecalis and E. faecium isolates was 22.7% and 77.3%, respectively. Remarkably increased incidence of aac(6')-aph(2") among HLGR isolates explains the relationship between this gene and the high level of resistance to aminoglycosides. As the resistant gene among enterococci can be transferred, the use of new-generation antibiotics is necessary.

  9. Antibacterial effects of gum kondagogu reduced/stabilized silver nanoparticles in combination with various antibiotics: a mechanistic approach

    Science.gov (United States)

    Rastogi, Lori; Kora, Aruna Jyothi; Sashidhar, R. B.

    2015-06-01

    Gum kondagogu reduced/stabilized silver nanoparticles (GK-AgNPs) were evaluated for their increased antibacterial and antibiofilm activities in combination with various antibiotics (ciprofloxacin, streptomycin and gentamicin) against Gram-positive ( Staphylococcus aureus 25923, Staphylococcus aureus 49834) and Gram-negative ( Escherichia coli 25922, Pseudomonas aeruginosa 27853) bacteria. The micro-broth dilution assay suggested an enhanced antibacterial activity of GK-AgNPs in combination with ciprofloxacin and aminoglycosides (streptomycin and gentamicin) against tested strains. Though the antibacterial activity of GK-AgNPs was found to increase significantly in the presence of antibiotics, the % enhancement was found to depend on both types of antibiotic and bacterial strain. It was also found that GK-AgNPs (1 µg/mL) in combination with various antibiotics at sub-MIC concentrations could inhibit 70 % of the bacterial biofilm formation as compared to respective controls. The enhanced antibacterial activity was due to the increased production of intracellular reactive oxygen species in bacteria when treated with a combination of GK-AgNPs and streptomycin as compared to individual treatment. The increased oxidative stress led to increased membrane damage as assessed by live/dead assay and higher levels of potassium ion release from the cells treated with both silver nanoparticles and streptomycin. The results suggested that the combination of antibiotics with GK-AgNPs has an enhanced antibacterial action. Further, the GK-AgNPs were found to be biocompatible up to a concentration of 2.5 µg/mL as assessed with MTT assay on HeLa cell line. The results suggest that GK-AgNPs could potentially be used as in vivo antibacterial agent in combination with antibiotics to overcome the problem of antibiotic resistance.

  10. Improving antibiotic activity against wound pathogens with manuka honey in vitro.

    Directory of Open Access Journals (Sweden)

    Rowena Jenkins

    Full Text Available Following the discovery of synergistic action between oxacillin and manuka honey against methicillin-resistant Staphylococcus aureus, this study was undertaken to search for further synergistic combinations of antibiotics and honey that might have potential in treating wounds. Fifteen antibiotics were tested with and without sublethal concentrations of manuka honey against each of MRSA and Pseudomonas aeruginosa using disc diffusion, broth dilution, E strip, chequerboard titration and growth curves. Five novel antibiotic and manuka honey combinations were found that improved antibacterial effectiveness in vitro and these offer a new avenue of future topical treatments for wound infections caused by these two important pathogens.

  11. Active educational intervention as a tool to improve safe and appropriate use of antibiotics

    Directory of Open Access Journals (Sweden)

    Mayadah B. Shehadeh

    2016-09-01

    It is concluded that using tailored education material targeting antibiotic need and use with a major aim of improving the public knowledge about antibiotics can be an effective and feasible strategy. This pilot study could be considered as the starting point for a wider scale public educational intervention study and national antibiotic campaign. However, the improvement in participant’s knowledge might not reflect an actual change in antibiotics–seeking behaviour or future retention of knowledge. Future research should seek to assess the impact of education on participant’s behaviour.

  12. Assessment of some cultural experimental methods to study the effects of antibiotics on microbial activities in a soil: An incubation study

    Science.gov (United States)

    Molaei, Ali; Haghnia, Gholamhosain; Astaraei, Alireza; Rasouli-Sadaghiani, MirHassan; Teresa Ceccherini, Maria; Datta, Rahul

    2017-01-01

    Oxytetracycline (OTC) and sulfamethoxazole (SMX) are two of most widely used antibiotics in livestock and poultry industry. After consumption of antibiotics, a major portion of these compounds is excreted through the feces and urine of animals. Land application of antibiotic-treated animal wastes has caused increasing concern about their adverse effects on ecosystem health. In this regard, inconsistent results have been reported regarding the effects of antibiotics on soil microbial activities. This study was conducted based on the completely randomized design to the measure microbial biomass carbon, cumulative respiration and iron (III) reduction bioassays. Concentrations of OTC and SMX including 0, 1, 10, 25, 50, and 100 mg/kg were spiked in triplicate to a sandy loam soil and incubated for 21 days at 25°C. Results showed that the effects of OTC and SMX antibiotics on cumulative respiration and microbial biomass carbon were different. SMX antibiotic significantly affected soil microbial biomass carbon and cumulative respiration at different treatments compared to control with increasing incubation time. OTC antibiotic, on the other hand, negatively affected cumulative respiration compared to control treatment throughout the incubation period. Although OTC antibiotic positively affected microbial biomass carbon at day one of incubation, there was no clear trend in microbial biomass carbon between different treatments of this antibiotic after that time period. Nevertheless, sulfamethoxazole and oxytetracycline antibiotics had similar effects on iron (III) reduction such that they considerably affected iron (III) reduction at 1 and 10 mg/kg, and iron (III) reduction was completely inhibited at concentrations above 10 mg/kg. Hence, according to our results, microbial biomass carbon and cumulative respiration experiments are not able alone to exhibit the effect of antibiotics on soil microbial activity, but combination of these two experiments with iron (III

  13. THE EFFECT OF GROWTH PARAMETERS ON THE ANTIBIOTIC ACTIVITY AND SPORULATION IN BACILLUS SPP. ISOLATED FROM SOIL

    Directory of Open Access Journals (Sweden)

    Alev Usta

    2013-04-01

    Full Text Available Fifty-two Bacillus strains, which were isolated from different soil samples, were screened for antibiotic properties. The Bacillus strains were checked for antibacterial properties by the cross-streak method against 5 test pathogens, and 25 Bacillus strains had an effect on the test microorganisms. One strain of Bacillus, which exhibited the largest inhibition zone (25 mm against Shigella sonnei, was named Bacillus sp. EA62. The antibacterial activity from Bacillus sp. EA62 was tested in six different culture media against Shigella sonnei using the agar well diffusion method. The best activity medium was selected and used for further studies. The influence of the incubation period, pH, and different glucose and nitrogen concentrations on the antibacterial activity was studied. The optimal conditions for the strongest antibiotic activity were found to be 72 hours (18 mm, pH 7.5 (23 mm, 3% glucose (25 mm, and 0.3% nitrogen concentration (23 mm. Additionally, the relationship between the antibiotic activity and sporulation was investigated. Accordingly, it was determined that the increase of the activity paralleled sporulation.

  14. The spatial profiles and metabolic capabilities of microbial populations impact the growth of antibiotic-resistant mutants

    Science.gov (United States)

    Kaushik, Karishma S.; Ratnayeke, Nalin; Katira, Parag; Gordon, Vernita D.

    2015-01-01

    Antibiotic resistance adversely affects clinical and public health on a global scale. Using the opportunistic human pathogen Pseudomonas aeruginosa, we show that increasing the number density of bacteria, on agar containing aminoglycoside antibiotics, can non-monotonically impact the survival of antibiotic-resistant mutants. Notably, at high cell densities, mutant survival is inhibited. A wide range of bacterial species can inhibit antibiotic-resistant mutants. Inhibition results from the metabolic breakdown of amino acids, which results in alkaline by-products. The consequent increase in pH acts in conjunction with aminoglycosides to mediate inhibition. Our work raises the possibility that the manipulation of microbial population structure and nutrient environment in conjunction with existing antibiotics could provide therapeutic approaches to combat antibiotic resistance. PMID:25972434

  15. Evaluation of the Antimicrobial Activity of Different Antibiotics Enhanced with Silver-Doped Hydroxyapatite Thin Films

    Directory of Open Access Journals (Sweden)

    Daniela Predoi

    2016-09-01

    Full Text Available The inhibitory and antimicrobial effects of silver particles have been known since ancient times. In the last few years, a major health problem has arisen due to pathogenic bacteria resistance to antimicrobial agents. The antibacterial activities of new materials including hydroxyapatite (HAp, silver-doped hydroxyapatite (Ag:HAp and various types of antibiotics such as tetracycline (T-HAp and T-Ag:HAp or ciprofloxacin (C-HAp and C-Ag:HAp have not been studied so far. In this study we reported, for the first time, the preparation and characterization of various thin films based on hydroxyapatite and silver-doped hydroxyapatite combined with tetracycline or ciprofloxacin. The structural and chemical characterization of hydroxyapatite and silver-doped hydroxyapatite thin films has been evaluated by X-ray diffraction (XRD and Fourier transform infrared spectroscopy (FTIR. The morphological studies of the HAp, Ag:HAp, T-HAp, T-Ag:HAp, C-HAp and C-Ag:HAp thin solid films were performed using scanning electron microscopy (SEM. In order to study the chemical composition of the coatings, energy dispersive X-ray analysis (EDX and glow discharge optical emission spectroscopy (GDOES measurements have been used, obtaining information on the distribution of the elements throughout the film. These studies have confirmed the purity of the prepared hydroxyapatite and silver-doped hydroxyapatite thin films obtained from composite targets containing Ca10−xAgx(PO46(OH2 with xAg = 0 (HAp and xAg = 0.2 (Ag:HAp. On the other hand, the major aim of this study was the evaluation of the antibacterial activities of ciprofloxacin and tetracycline in the presence of HAp and Ag:HAp thin layers against Staphylococcus aureus and Escherichia coli strains. The antibacterial activities of ciprofloxacin and tetracycline against Staphylococcus aureus and Escherichia coli test strains increased in the presence of HAp and Ag:HAp thin layers.

  16. The antibiotic polymyxin B exhibits novel antifungal activity against Fusarium species.

    Science.gov (United States)

    Hsu, Li-Hang; Wang, Hsuan-Fu; Sun, Pei-Lun; Hu, Fung-Rong; Chen, Ying-Lien

    2017-06-01

    The genus Fusarium comprises many species, including Fusarium oxysporum, Fusarium solani, Fusarium graminearum and Fusarium verticillioides, and causes severe infections in plants and humans. In clinical settings, Fusarium is the third most frequent mould to cause invasive fungal infections after Aspergillus and the Mucorales. F. solani and F. oxysporum are the most prevalent Fusarium spp. causing clinical disease. However, few effective antifungal drugs are available to treat human and plant Fusarium infections. The cationic peptide antibiotic polymyxin B (PMB) exhibits antifungal activity against the human fungal pathogens Candida albicans and Cryptococcus neoformans, but its efficacy against Fusarium spp. is unknown. In this study, the antifungal activity of PMB was tested against 12 Fusarium strains that infect humans and plants (banana, tomato, melon, pea, wheat and maize). PMB was fungicidal against all 12 Fusarium strains, with minimum fungicidal concentrations of 32 µg/mL or 64 µg/mL for most strains tested, as evidenced by broth dilution, methylene blue staining and XTT reduction assays. PMB can reduce the germination rates of conidia, but not chlamydospores, and can cause defects in cell membrane integrity in Fusarium strains. PMB exhibits synergistic activity with posaconazole and can potentiate the effect of fluconazole, voriconazole or amphotericin B against Fusarium spp. However, PMB does not show synergistic effects with fluconazole against Fusarium spp. as it does against Candida glabrata and C. neoformans, indicating evolutionary divergence of mechanisms between yeast pathogens and the filamentous fungus Fusarium. Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  17. Antibiotic policy

    OpenAIRE

    Gyssens, Inge

    2011-01-01

    There is a clear association between antibiotic use and resistance both on individual and population levels. In the European Union, countries with large antibiotic consumption have higher resistance rates. Antibiotic resistance leads to failed treatments, prolonged hospitalisations, increased costs and deaths. With few new antibiotics in the Research & Development pipeline, prudent antibiotic use is the only option to delay the development of resistance. Antibiotic policy consists of prescrib...

  18. ISOLATION AND CHARACTERIZATION OF STREPTOMYCES RISHIRIENSIS (VY31 WITH ANTIBIOTIC ACTIVITY AGAINST VARIOUS PATHOGENIC MICROORGANISMS

    Directory of Open Access Journals (Sweden)

    Ivana Charousová

    2015-02-01

    Full Text Available Actinomycete strain VY31 was isolated from agriculture soil of region Východná, Slovakia. Morphological, physiological and biochemical studies indicated that this isolate belongs to the genus Streptomyces. The 16S rRNA sequence data supported the assignment of the isolate to the genus Streptomyces rishiriensis (sequence similarity 97%. Tested isolate was able to produce melanin dark pigment and exopigments on ISP6, ISP7 and SSM+T cultivating media. The optimal pH range was from 6-8 and optimal temperature at 30 °C. The strain exhibited salt tolerance up to 5 % and utilized the carbon sources such as glucose, arabinose, xylose, inositol, mannose, fructose, rhamnose and rafinose. Using ApiZym® stripes, the highest production of enzymes was determined for phosphatase alkaline, leucinearylamidase, valinearylamidase, phosphatase acid, naphtol-AS-BI-phosphohydrolase, galactosidase and glucosidase (>40 nmol. According to ApiCoryne® results, positive reaction was confirmed in case of esculin, alkaline phosphatase, and this strain was also able to hydrolyze gelatine. Minimum Inhibitory Concentration (MIC of the purified extract of isolate was evaluated against Gram-positive bacteria Staphylococcus aureus and Enterococcus faecium, Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa and against yeast Candida albicans. On the basis of MIC results, strain VY31 had noticeable antibacterial activity against Staphylococcus aures N315 (MRSA from collection database of University Hospital in Hamburg, Germany. This isolate could be used in the development of new antibiotics for pharmaceutical purposes.

  19. Diverse modulation of spa transcription by cell wall active antibiotics in Staphylococcus aureus

    DEFF Research Database (Denmark)

    Nielsen, Lene Nørby; Roggenbuck, Michael; Haaber, Jakob Krause

    2012-01-01

    ABSTRACT: BACKGROUND: The aim of this study was to investigate the effect of various classes of clinically relevant antibiotics at sub-lethal concentrations on virulence gene expression and biofilm formation in Staphylococcus aureus. FINDINGS: LacZ promoter fusions of genes related...... to staphylococcal virulence were used to monitor the effects of antibiotics on gene expression in a disc diffusion assay. The selected genes were hla and spa encoding alpha-hemolysin and Protein A, respectively and RNAIII, the effector molecule of the agr quorum sensing system. The results were confirmed...... by quantitative real-time PCR. Additionally, we monitored the effect of subinhibitory concentrations of antibiotics on the ability of S. aureus to form biofilm in a microtiter plate assay. The results show that sub-lethal antibiotic concentrations diversely modulate expression of RNAIII, hla and spa. Consistently...

  20. In vitro anti-inflammatory and anti-coagulant effects of antibiotics towards Platelet Activating Factor and thrombin

    Science.gov (United States)

    2011-01-01

    Background Sepsis is characterized as a systemic inflammatory response that results from the inability of the immune system to limit bacterial spread during an ongoing infection. In this condition the significant mediator of inflammation Platelet Activating Factor (PAF) and the coagulant factor thrombin are implicated. In animal models, treatment with PAF-antagonists or co-administration of antibiotics with recombinant-PAF-Acetylhydrolase (rPAF-AH) have exhibited promising results. In order to examine the putative anti-inflammatory and/or antithrombotic interactions between antibiotic treatment used in sepsis with PAF and/or thrombin, we studied the in vitro effects of these compounds towards PAF or/and thrombin related activities and towards PAF basic metabolic enzymes. Methods We assessed the inhibitory effect of these drugs against PAF or thrombin induced aggregation on washed rabbit platelets (WRPs) or rabbit Platelet Reach Plasma (rPRP) by evaluating their IC50 values. We also studied their effect on Cholinephosphotransferase of PAF (PAF-CPT)/Lyso-PAF-Acetyltransferase (Lyso-PAF-AT) of rabbit leukocytes (RLs), as well as on rabbit plasma-PAF-AH, the key enzymes of both de novo/remodelling PAF biosynthesis and PAF degradation, respectively. Results Several antibiotics inhibited PAF-induced platelet aggregation of both WRPs and rPRP in a concentration-depended manner, with clarithromycin, azithromycin and amikacin exhibiting the higher inhibitory effect, while when combined they synergistically inhibited PAF. Higher concentrations of all antibiotics tested were needed in order to inhibit PAF induced aggregation of rPRP, but also to inhibit thrombin induced aggregation of WRPs. Concentrations of these drugs similar to their IC50 values against PAF activity in WRPs, inhibited also in vitro PAF-CPT and Lyso-PAF-AT activities of rabbit leukocytes, while only clarithromycin and azithromycin increased rabbit plasma-PAF-AH activity. Conclusions These newly found

  1. Occurrence of aminoglycoside-modifying enzymes among isolates of Escherichia coli exhibiting high levels of aminoglycoside resistance isolated from Korean cattle farms.

    Science.gov (United States)

    Belaynehe, Kuastros Mekonnen; Shin, Seung Won; Hong-Tae, Park; Yoo, Han Sang

    2017-08-01

    This study investigated 247 Escherichia coli isolates collected from four cattle farms to characterize aminoglycoside-modifying enzyme (AME) genes, their plasmid replicons and transferability. Out of 247 isolates a high number of isolates (total 202; 81.78%) were found to be resistant to various antibiotics by disc diffusion. Of the 247 strains, 139 (56.3%) were resistant to streptomycin, and other antibiotic resistances followed as tetracycline (12.15%), ampicillin (7%), chloramphenicol (5.7%) and trimethoprim-sulfamethoxazole (0.8%). Among 247 isolates B1 was the predominant phylogenetic group identified comprising 151 isolates (61.1%), followed by groups A (27.9%), D (7%) and B2 (4%). Out of 139 isolates investigated for AME, 130 (93.5%) isolates carried at least one AME gene. aph3″-1a and aph3″-1b (46%) were the principal genes detected, followed by aac3-IVa (34.5%). ant2″-1a was the least detected gene (2.2%). Nine (6.5%) strains carried no AME genes. Twelve (63.2%) among 19 isolates transferred an AME gene to a recipient and aph3΄-1a was the dominant transferred gene. Transferability mainly occurred via the IncFIB replicon type (52.6%). Pulsed-field gel electrophoresis typing demonstrated a higher degree of diversity with 14 distinct cluster types. This result suggests that commensal microflora from food-producing animals has a tremendous ability to harbor and transfer AME genes, and poses a potential risk by dissemination of resistance to humans through the food chain. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Structure of the bifunctional aminoglycoside-resistance enzyme AAC(6′)-Ie-APH(2′′)-Ia revealed by crystallographic and small-angle X-ray scattering analysis

    Science.gov (United States)

    Smith, Clyde A.; Toth, Marta; Weiss, Thomas M.; Frase, Hilary; Vakulenko, Sergei B.

    2014-01-01

    Broad-spectrum resistance to aminoglycoside antibiotics in clinically important Gram-positive staphylococcal and entero­coccal pathogens is primarily conferred by the bifunctional enzyme AAC(6′)-Ie-APH(2′′)-Ia. This enzyme possesses an N-terminal coenzyme A-dependent acetyltransferase domain [AAC(6′)-Ie] and a C-terminal GTP-dependent phosphotransferase domain [APH(2′′)-Ia], and together they produce resistance to almost all known aminoglycosides in clinical use. Despite considerable effort over the last two or more decades, structural details of AAC(6′)-Ie-APH(2′′)-Ia have remained elusive. In a recent breakthrough, the structure of the isolated C-terminal APH(2′′)-Ia enzyme was determined as the binary Mg2GDP complex. Here, the high-resolution structure of the N-terminal AAC(6′)-Ie enzyme is reported as a ternary kanamycin/coenzyme A abortive complex. The structure of the full-length bifunctional enzyme has subsequently been elucidated based upon small-angle X-ray scattering data using the two crystallographic models. The AAC(6′)-Ie enzyme is joined to APH(2′′)-Ia by a short, predominantly rigid linker at the N-terminal end of a long α-helix. This α-helix is in turn intrinsically associated with the N-terminus of APH(2′′)-Ia. This structural arrangement supports earlier observations that the presence of the intact α-helix is essential to the activity of both functionalities of the full-length AAC(6′)-Ie-APH(2′′)-Ia enzyme. PMID:25286858

  3. Enabling techniques in the search for new antibiotics: Combinatorial biosynthesis of sugar-containing antibiotics.

    Science.gov (United States)

    Park, Je Won; Nam, Sang-Jip; Yoon, Yeo Joon

    2017-06-15

    Nature has a talent for inventing a vast number of natural products, including hybrids generated by blending different scaffolds, resulting in a myriad of bioactive chemical entities. Herein, we review the highlights and recent trends (2010-2016) in the combinatorial biosynthesis of sugar-containing antibiotics where nature's structural diversification capabilities are exploited to enable the creation of new anti-infective and anti-proliferative drugs. In this review, we describe the modern combinatorial biosynthetic approaches for polyketide synthase-derived complex and aromatic polyketides, non-ribosomal peptide synthetase-directed lipo-/glycopeptides, aminoglycosides, nucleoside antibiotics, and alkaloids, along with their therapeutic potential. Finally, we present the feasible nexus between combinatorial biosynthesis, systems biology, and synthetic biology as a toolbox to provide new antibiotics that will be indispensable in the post-antibiotic era. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Anti-biofilm activity and synergism of novel thiazole compounds with glycopeptide antibiotics against multidrug-resistant staphylococci

    Science.gov (United States)

    Mohammad, Haroon; Mayhoub, Abdelrahman S.; Cushman, Mark; Seleem, Mohamed N.

    2015-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) infections are a leading cause of death among all fatalities caused by antibiotic-resistant bacteria. With the rise of increasing resistance to current antibiotics, new antimicrobials and treatment strategies are urgently needed. Thiazole compounds have been shown to possess potent antimicrobial activity. A lead thiazole 1 and a potent derivative 2 were synthesized and their activity in combination with glycopeptide antibiotics was determined against an array of MRSA and vancomycin-resistant Staphylococcus aureus (VRSA) clinical isolates. Additionally, the anti-biofilm activity of the novel thiazoles was investigated against Staphylococcus epidermidis. Compound 2 behaved synergistically with vancomycin against MRSA and was able to re-sensitize VRSA to vancomycin, reducing its minimum inhibitory concentration (MIC) by 512-fold in two strains. Additionally, both thiazole compounds were superior to vancomycin in significantly reducing S. epidermidis biofilm mass. Collectively the results obtained demonstrate compounds 1 and 2 possess potent antimicrobial activity alone or in combination with vancomycin against multidrug-resistant staphylococci and show potential for use in disrupting staphylococcal biofilm. PMID:25315757

  5. ANTIBACTERIAL ACTIVITY OF SOME WILD MEDICAL PLANTS EXTRACT TO ANTIBIOTIC RESISTANT ESCHERICHIA COLI

    Directory of Open Access Journals (Sweden)

    Lukáš Hleba

    2013-02-01

    Full Text Available Antibiotics are probably the most successful family of drugs so far developed for improving human health. Because of increasing resistance to antibiotics of many bacteria, plant extracts and plant compounds are of new interest as antiseptics and antimicrobial agents in medicine. In this study, we researched antimicrobial effects of extracts of some medical plants (Tussilagofarfara, Equisetum arvense, Sambucusnigra, Aesculushippocastanumand Taraxacumofficinale from Slovakia to antibiotic resistant and antibiotic sensitive bacteria isolated from milk of cows and mare, which were breeded in different conditions. Microorganisms which were used in this experiment we isolated from milk from conventional breeding of cows (tenE. coli strains and from ecological breeding of Lipicanmare (tenE. coli strains by sterile cotton swabs. For antibiotic susceptibility testing was used disc diffusion method according by EUCAST. After dried at room temperature we weighed 50 g of crushed medical plants (parts and it were to extract in 400 ml methanol for two weeks at room temperature. For antimicrobial susceptibility testing of medical plants extract blank discs with 6 mm diameter disc diffusion method was used. We determined that all Escherichia coli strains isolated from milk of conventional breeding of cows were resistant to ampicillin and chloramphenicol. We determined that all tested ampicillin and chloramphenicol resistant E. coli strains isolated from conventional breeding of cow showed susceptibility to all used medical plants extracts. In difference, we determined that antibiotic susceptible E. coli strains isolated from ecological breeding of Lipicanmare were susceptible to Tussilagofarfara extract only. From these results we could be conclude some observations, which could be important step in treatment of bacterial infections caused by antibiotic resistant bacteria and it could be important knowledge for treatment of livestock in conventional breeding

  6. Carbon Sources Tune Antibiotic Susceptibility in Pseudomonas aeruginosa via Tricarboxylic Acid Cycle Control

    OpenAIRE

    Meylan, Sylvain; Porter, Caroline B.M.; Yang, Jason H.; Belenky, Peter; Gutierrez, Arnaud; Lobritz, Michael A.; Park, Jihye; Kim, Sun H.; Moskowitz, Samuel M.; Collins, James J.

    2017-01-01

    Metabolically dormant bacteria present a critical challenge to effective antimicrobial therapy because these bacteria are genetically susceptible to antibiotic treatment but phenotypically tolerant. Such tolerance has been attributed to impaired drug uptake, which can be reversed by metabolic stimulation. Here, we evaluate the effects of central carbon metabolite stimulations on aminoglycoside sensitivity in the pathogen Pseudomonas aeruginosa. We identify fumarate as a tobramycin potentiator...

  7. A Comprehensive Insight into Tetracycline Resistant Bacteria and Antibiotic Resistance Genes in Activated Sludge Using Next-Generation Sequencing

    OpenAIRE

    Huang, Kailong; Tang, Junying; Zhang, Xu-Xiang; Xu, Ke; Ren, Hongqiang

    2014-01-01

    In order to comprehensively investigate tetracycline resistance in activated sludge of sewage treatment plants, 454 pyrosequencing and Illumina high-throughput sequencing were used to detect potential tetracycline resistant bacteria (TRB) and antibiotic resistance genes (ARGs) in sludge cultured with different concentrations of tetracycline. Pyrosequencing of 16S rRNA gene revealed that tetracycline treatment greatly affected the bacterial community structure of the sludge. Nine genera cons...

  8. Bactericidal activity and post-antibiotic effect of ozenoxacin against Propionibacterium acnes.

    Science.gov (United States)

    Kanayama, Shoji; Okamoto, Kazuaki; Ikeda, Fumiaki; Ishii, Ritsuko; Matsumoto, Tatsumi; Hayashi, Naoki; Gotoh, Naomasa

    2017-06-01

    Ozenoxacin, a novel non-fluorinated topical quinolone, is used for the treatment of acne vulgaris in Japan. We investigated bactericidal activity and post-antibiotic effect (PAE) of ozenoxacin against Propionibacterium acnes, a major causative bacterium of acne vulgaris. The minimum inhibitory concentrations (MICs) of ozenoxacin against 3 levofloxacin-susceptible strains (MIC of levofloxacin; ≤4 μg/mL) and 3 levofloxacin-resistant strains (MIC of levofloxacin; ≥8 μg/mL) ranged from 0.03 to 0.06 μg/mL and from 0.25 to 0.5 μg/mL, respectively. These MICs of ozenoxacin were almost the same or lower than nadifloxacin and clindamycin. The minimum bactericidal concentrations (MBCs) of ozenoxacin against the levofloxacin-susceptible and -resistant strains were from 0.06 to 8 μg/mL and from 0.5 to 4 μg/mL, respectively. These MBCs were lower than those of nadifloxacin and clindamycin. In time-kill assay, ozenoxacin at 1/4, 1 and 4 times the respective MIC against both levofloxacin-susceptible and -resistant strains showed a concentration-dependent bactericidal activity. Ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains showed more potent and more rapid onset of bactericidal activity compared to nadifloxacin and clindamycin at 4 times the respective MICs. The PAEs of ozenoxacin at 4 times the MICs against the levofloxacin-susceptible strains were from 3.3 to 17.1 h, which were almost the same or longer than nadifloxacin and clindamycin. In contrast, the PAEs were hardly induced by any antimicrobial agents against the levofloxacin-resistant strains. The present findings suggest that ozenoxacin has a potent bactericidal activity against both levofloxacin-susceptible and -resistant P. acnes, and a long-lasting PAE against levofloxacin-susceptible P. acnes. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  9. The Sensitivity to Aminoglycosides and Heavy Metals of Isolates of ...

    African Journals Online (AJOL)

    Eighty-two clinical isolates of Pseudomonas aeruginosa strains were tested for their sensitivity to aminoglycosides by an agar diffusion method and to heavy metals by a dilution technique on tri –buffered mineral salt agar containing 10 – 100mg/L CdCl2.H20, CoCl2.6H20, ZnCl2, AgNO3 and HgCl2. All the strains tested ...

  10. Polyprenols of Ginkgo biloba Enhance Antibacterial Activity of Five Classes of Antibiotics.

    Science.gov (United States)

    Tao, Ran; Wang, Chengzhang; Ye, Jianzhong; Zhou, Hao; Chen, Hongxia

    2016-01-01

    Polyprenol (GBP) from Ginkgo biloba Leaves (GBL) is an important lipid with many bioactive effects. The effect of GBP on antibacterial properties of five antibiotics belonging to different classes was through analysis of inhibition halos, MIC, and FIC index. And we studied the time-killing curves and Ca(2+) mobilization assay in Staphylococcus aureus cells treated with GBP microemulsion and gentamicin sulfate under MIC/2 conditions. These results showed that the GBP microemulsion (average diameter 90.2 nm) combining with gentamicin sulfate had the highest enhancing antibacterial effect against Staphylococcus aureus, and the MIC value was 33.0 μg/mL. The increase of the antibacterial effect of tested antibiotics was positively correlated with the decrease of the average diameter of GBP microemulsion. Moreover, GBP microemulsion enhanced antibacterial effect and prolonged antibacterial time of GBP combining with gentamicin sulfate against Staphylococcus aureus. GBP microemulsion could enhance the ability of gentamicin inducing an increase in intracellular calcium concentrations to Staphylococcus aureus. GBP microemulsion could help some classes of antibiotics to inhibit or kill bacteria. This study supports the fact that GBP microemulsion obviously can not only reduce the dosage of some classes of antibiotics, but also reduce the frequency of the antibiotic use in vitro.

  11. Polyprenols of Ginkgo biloba Enhance Antibacterial Activity of Five Classes of Antibiotics

    Directory of Open Access Journals (Sweden)

    Ran Tao

    2016-01-01

    Full Text Available Polyprenol (GBP from Ginkgo biloba Leaves (GBL is an important lipid with many bioactive effects. The effect of GBP on antibacterial properties of five antibiotics belonging to different classes was through analysis of inhibition halos, MIC, and FIC index. And we studied the time-killing curves and Ca2+ mobilization assay in Staphylococcus aureus cells treated with GBP microemulsion and gentamicin sulfate under MIC/2 conditions. These results showed that the GBP microemulsion (average diameter 90.2 nm combining with gentamicin sulfate had the highest enhancing antibacterial effect against Staphylococcus aureus, and the MIC value was 33.0 μg/mL. The increase of the antibacterial effect of tested antibiotics was positively correlated with the decrease of the average diameter of GBP microemulsion. Moreover, GBP microemulsion enhanced antibacterial effect and prolonged antibacterial time of GBP combining with gentamicin sulfate against Staphylococcus aureus. GBP microemulsion could enhance the ability of gentamicin inducing an increase in intracellular calcium concentrations to Staphylococcus aureus. GBP microemulsion could help some classes of antibiotics to inhibit or kill bacteria. This study supports the fact that GBP microemulsion obviously can not only reduce the dosage of some classes of antibiotics, but also reduce the frequency of the antibiotic use in vitro.

  12. Ceftriaxone Potentiates Warfarin Activity Greater Than Other Antibiotics in the Treatment of Urinary Tract Infections.

    Science.gov (United States)

    Saum, Lindsay M; Balmat, Ryan P

    2016-04-01

    The cephalosporin class has been associated with an increased risk of bleeding among elderly patients receiving warfarin. Urinary tract infections (UTI) are the most prevalent infection in elderly patients. To determine the extent of interaction between antibiotics used in the treatment of UTI, particularly specific cephalosporins and warfarin. A retrospective chart review was conducted on chronic warfarin patients with a diagnosis of UTI treated with ceftriaxone, a first-generation cephalosporin, penicillin, or ciprofloxacin. The primary outcome was the comparison of the extent of international normalized ratio (INR) change from baseline between each antibiotic group. The ceftriaxone group was found to have a statistically significant higher peak INR value compared to all other studied antibiotics (ceftriaxone: 3.56, first-generation cephalosporins: 2.66, penicillins: 2.98, ciprofloxacin: 2.3; P = .004), a statistically significant greater extent of change in INR value (+1.19, +0.66, +0.8, +0.275; P = .006), and a statistically significant greater percentage change in INR value when compared to ciprofloxacin (54.4% vs 12.7%; P = .037). Ceftriaxone interacts with warfarin to increase a patient's INR value more than other commonly administered antibiotics for UTI treatment. Other antibiotics should be preferred for UTI treatment in patients on warfarin. © The Author(s) 2014.

  13. Characterization of paired mucoid/non-mucoid Pseudomonas aeruginosa isolates from Danish cystic fibrosis patients: antibiotic resistance, beta-lactamase activity and RiboPrinting

    DEFF Research Database (Denmark)

    Ciofu, O; Fussing, V; Bagge, N

    2001-01-01

    before 1991 had an antibiotic susceptibility pattern similar to the 1997 isolates. Despite prolonged and intensive antibiotic treatment, susceptible mucoid isolates were isolated from the CF sputum, possibly because these bacteria are protected from the selective pressure of antibiotics by the resistant......The purpose of this study was to characterize 42 paired mucoid and non-mucoid Danish cystic fibrosis (CF) Pseudomonas aeruginosa isolates collected in 1997, by RiboPrinting, antibiotic susceptibility and beta-lactamase activity. Eight P. aeruginosa isolates collected before 1991 were included...... for comparison. Eighteen of the 42 paired mucoid and non-mucoid isolates showed the same ribotype; the remaining 24 belonged to different ribogroups. Mucoid isolates showed higher susceptibility to antibiotics and lower beta-lactamase activity compared with non-mucoid isolates. Significant differences (P...

  14. Interspecies signalling: Pseudomonas putida efflux pump TtgGHI is activated by indole to increase antibiotic resistance.

    Science.gov (United States)

    Molina-Santiago, Carlos; Daddaoua, Abdelali; Fillet, Sandy; Duque, Estrella; Ramos, Juan-Luis

    2014-05-01

    In Gram-negative bacteria, multidrug efflux pumps are responsible for the extrusion of chemicals that are deleterious for growth. Some of these efflux pumps are induced by endogenously produced effectors, while abiotic or biotic signals induce the expression of other efflux pumps. In Pseudomonas putida, the TtgABC efflux pump is the main antibiotic extrusion system that respond to exogenous antibiotics through the modulation of the expression of this operon mediated by TtgR. The plasmid-encoded TtgGHI efflux pump in P. putida plays a minor role in antibiotic resistance in the parental strain; however, its role is critical in isogenic backgrounds deficient in TtgABC. Expression of ttgGHI is repressed by the TtgV regulator that recognizes indole as an effector, although P. putida does not produce indole itself. Because indole is not produced by Pseudomonas, the indole-dependent antibiotic resistance seems to be part of an antibiotic resistance programme at the community level. Pseudomonas putida recognizes indole added to the medium or produced by Escherichia coli in mixed microbial communities. Transcriptomic analyses revealed that the indole-specific response involves activation of 43 genes and repression of 23 genes. Indole enhances not only the expression of the TtgGHI pump but also a set of genes involved in iron homeostasis, as well as genes for amino acid catabolism. In a ttgABC-deficient P. putida, background ampicillin and other bactericidal compounds lead to cell death. Co-culture of E. coli and P. putida ΔttgABC allowed growth of the P. putida mutant in the presence of ampicillin because of induction of the indole-dependent efflux pump. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

  15. Short, Synthetic Cationic Peptides Have Antibacterial Activity against Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with Antibiotics.

    Science.gov (United States)

    Gupta, Kajal; Singh, Sameer; van Hoek, Monique L

    2015-08-24

    Multicellular organisms are constantly exposed to a multitude of pathogenic microbes. Infection is inhibited in vivo by the innate and adaptive immune system. Mycobacterium species have emerged that are resistant to most antibiotics. We identified several naturally occurring cationic antimicrobial peptides that were active at low micromolar concentrations against Mycobacterium smegmatis. Human-derived cathelicidin LL-37 is well characterized and studied against M. smegmatis; we compared LL-37 with Chinese cobra-derived cathelicidin NA-CATH and mouse cathelicidin (mCRAMP). Two synthetic 11-residue peptides (ATRA-1A and ATRA-2) containing variations of a repeated motif within NA-CATH were tested for their activity against M. smegmatis along with a short synthetic peptide derivative from the human beta-defensin hBD3 (hBD3-Pep4). We hypothesized that these smaller synthetic peptides may demonstrate antimicrobial effectiveness with shorter length (and at less cost), making them strong potential candidates for development into broad-spectrum antimicrobial compounds or use in combination with antibiotics. These peptides have antimicrobial activity with EC50 ranging from 0.05 to 1.88 μg/mL against Mycobacterium smegmatis. The ATRA-1A short peptide was found to be the most effective antimicrobial peptide (AMP) (EC50 = 0.05 μg/mL). High bactericidal activity correlated with bacterial membrane depolarization and permeabilization activities. The efficacy of the peptides was further analyzed through Minimal Inhibitory Concentration (MIC) assays. The MICs were determined by the microdilution method. The peptide mCRAMP showed the best MIC activity at 15.6 μg/mL. Neither of the effective short synthetic peptides demonstrated synergy with the antibiotic rifampicin, although both demonstrated synergy with the cyclic peptide antibiotic polymyxin B. The peptides LL-37 and mCRAMP displayed synergism with rifampicin in MIC assays, whereas antibiotic polymyxin B displayed synergism

  16. Short, Synthetic Cationic Peptides Have Antibacterial Activity against Mycobacterium smegmatis by Forming Pores in Membrane and Synergizing with Antibiotics

    Directory of Open Access Journals (Sweden)

    Kajal Gupta

    2015-08-01

    Full Text Available Multicellular organisms are constantly exposed to a multitude of pathogenic microbes. Infection is inhibited in vivo by the innate and adaptive immune system. Mycobacterium species have emerged that are resistant to most antibiotics. We identified several naturally occurring cationic antimicrobial peptides that were active at low micromolar concentrations against Mycobacterium smegmatis. Human-derived cathelicidin LL-37 is well characterized and studied against M. smegmatis; we compared LL-37 with Chinese cobra-derived cathelicidin NA-CATH and mouse cathelicidin (mCRAMP. Two synthetic 11-residue peptides (ATRA-1A and ATRA-2 containing variations of a repeated motif within NA-CATH were tested for their activity against M. smegmatis along with a short synthetic peptide derivative from the human beta-defensin hBD3 (hBD3-Pep4. We hypothesized that these smaller synthetic peptides may demonstrate antimicrobial effectiveness with shorter length (and at less cost, making them strong potential candidates for development into broad-spectrum antimicrobial compounds or use in combination with antibiotics. These peptides have antimicrobial activity with EC50 ranging from 0.05 to 1.88 μg/mL against Mycobacterium smegmatis. The ATRA-1A short peptide was found to be the most effective antimicrobial peptide (AMP (EC50 = 0.05 μg/mL. High bactericidal activity correlated with bacterial membrane depolarization and permeabilization activities. The efficacy of the peptides was further analyzed through Minimal Inhibitory Concentration (MIC assays. The MICs were determined by the microdilution method. The peptide mCRAMP showed the best MIC activity at 15.6 μg/mL. Neither of the effective short synthetic peptides demonstrated synergy with the antibiotic rifampicin, although both demonstrated synergy with the cyclic peptide antibiotic polymyxin B. The peptides LL-37 and mCRAMP displayed synergism with rifampicin in MIC assays, whereas antibiotic polymyxin B displayed

  17. Abundance of antibiotics, antibiotic resistance genes and bacterial community composition in wastewater effluents from different Romanian hospitals.

    Science.gov (United States)

    Szekeres, Edina; Baricz, Andreea; Chiriac, Cecilia Maria; Farkas, Anca; Opris, Ocsana; Soran, Maria-Loredana; Andrei, Adrian-Stefan; Rudi, Knut; Balcázar, Jose Luis; Dragos, Nicolae; Coman, Cristian

    2017-06-01

    Antimicrobial resistance represents a growing and significant public health threat, which requires a global response to develop effective strategies and mitigate the emergence and spread of this phenomenon in clinical and environmental settings. We investigated, therefore, the occurrence and abundance of several antibiotics and antibiotic resistance genes (ARGs), as well as bacterial community composition in wastewater effluents from different hospitals located in the Cluj County, Romania. Antibiotic concentrations ranged between 3.67 and 53.05 μg L -1 , and the most abundant antibiotic classes were β-lactams, glycopeptides, and trimethoprim. Among the ARGs detected, 14 genes confer resistance to β-lactams, aminoglycosides, chloramphenicol, macrolide-lincosamide-streptogramin B (MLSB) antibiotics, sulfonamides, and tetracyclines. Genes encoding quaternary ammonium resistance and a transposon-related element were also detected. The sulI and qacEΔ1 genes, which confer resistance to sulfonamides and quaternary ammonium, had the highest relative abundance with values ranging from 5.33 × 10 -2 to 1.94 × 10 -1 and 1.94 × 10 -2 to 4.89 × 10 -2 copies/16 rRNA gene copies, respectively. The dominant phyla detected in the hospital wastewater samples were Proteobacteria, Bacteroidetes, Firmicutes, and Actinobacteria. Among selected hospitals, one of them applied an activated sludge and chlorine disinfection process before releasing the effluent to the municipal collector. This conventional wastewater treatment showed moderate removal efficiency of the studied pollutants, with a 55-81% decrease in antibiotic concentrations, 1-3 order of magnitude lower relative abundance of ARGs, but with a slight increase of some potentially pathogenic bacteria. Given this, hospital wastewaters (raw or treated) may contribute to the spread of these emerging pollutants in the receiving environments. To the best of our knowledge, this study quantified for the first time the

  18. Antibacterial and Antibiotic-Modifying Activity of Methanol Extracts from Six Cameroonian Food Plants against Multidrug-Resistant Enteric Bacteria

    Directory of Open Access Journals (Sweden)

    Joachim K. Dzotam

    2017-01-01

    Full Text Available The present work was designed to investigate the antibacterial activities of methanol extracts from six Cameroonian edible plants and their synergistic effects with some commonly used antibiotics against multidrug-resistant (MDR Gram-negative bacteria expressing active efflux pumps. The extracts were subjected to qualitative phytochemical screening and the microdilution broth method was used for antibacterial assays. The results of phytochemical tests indicate that all tested crude extracts contained polyphenols, flavonoids, triterpenes, and steroids. Extracts displayed selective antibacterial activities with the minimal inhibitory concentration (MIC values ranging from 32 to 1024 μg/mL. The lowest MIC value (32 μg/mL was recorded with Coula edulis extract against E. coli AG102 and K. pneumoniae K2 and with Mangifera indica bark extract against P. aeruginosa PA01 and Citrus sinensis extract against E. coli W3110 which also displayed the best MBC (256 μg/mL value against E. coli ATCC8739. In combination with antibiotics, extracts from M. indica leaves showed synergistic effects with 75% (6/8 of the tested antibiotics against more than 80% of the tested bacteria. The findings of the present work indicate that the tested plants may be used alone or in combination in the treatment of bacterial infections including the multidrug-resistant bacteria.

  19. Synthesis, optimization, and characterization of silver nanoparticles from Acinetobacter calcoaceticus and their enhanced antibacterial activity when combined with antibiotics.

    Science.gov (United States)

    Singh, Richa; Wagh, Priyanka; Wadhwani, Sweety; Gaidhani, Sharvari; Kumbhar, Avinash; Bellare, Jayesh; Chopade, Balu Ananda

    2013-01-01

    The development of nontoxic methods of synthesizing nanoparticles is a major step in nanotechnology to allow their application in nanomedicine. The present study aims to biosynthesize silver nanoparticles (AgNPs) using a cell-free extract of Acinetobacter spp. and evaluate their antibacterial activity. Eighteen strains of Acinetobacter were screened for AgNP synthesis. AgNPs were characterized using various techniques. Reaction parameters were optimized, and their effect on the morphology of AgNPs was studied. The synergistic potential of AgNPs on 14 antibiotics against seven pathogens was determined by disc-diffusion, broth-microdilution, and minimum bactericidal concentration assays. The efficacy of AgNPs was evaluated as per the minimum inhibitory concentration (MIC) breakpoints of the Clinical and Laboratory Standards Institute (CLSI) guidelines. Only A. calcoaceticus LRVP54 produced AgNPs within 24 hours. Monodisperse spherical nanoparticles of 8-12 nm were obtained with 0.7 mM silver nitrate at 70°C. During optimization, a blue-shift in ultraviolet-visible spectra was seen. X-ray diffraction data and lattice fringes (d =0.23 nm) observed under high-resolution transmission electron microscope confirmed the crystallinity of AgNPs. These AgNPs were found to be more effective against Gram-negative compared with Gram-positive microorganisms. Overall, AgNPs showed the highest synergy with vancomycin in the disc-diffusion assay. For Enterobacter aerogenes, a 3.8-fold increase in inhibition zone area was observed after the addition of AgNPs with vancomycin. Reduction in MIC and minimum bactericidal concentration was observed on exposure of AgNPs with antibiotics. Interestingly, multidrug-resistant A. baumannii was highly sensitized in the presence of AgNPs and became susceptible to antibiotics except cephalosporins. Similarly, the vancomycin-resistant strain of Streptococcus mutans was also found to be susceptible to antibiotic treatment when AgNPs were added. These

  20. Activation of ClpP protease by ADEP antibiotics: insights from hydrogen exchange mass spectrometry.

    Science.gov (United States)

    Sowole, Modupeola A; Alexopoulos, John A; Cheng, Yi-Qiang; Ortega, Joaquin; Konermann, Lars

    2013-11-15

    The bacterial protease ClpP consists of 14 subunits that assemble into two stacked heptameric rings. The central degradation chamber can be accessed via axial pores. In free ClpP, these pores are obstructed by the N-terminal regions of the seven subunits at either end of the barrel. Acyldepsipeptides (ADEPs) are antibacterial compounds that bind in hydrophobic clefts surrounding the pore region, causing the pores to open up. The ensuing uncontrolled degradation of intracellular proteins is responsible for the antibiotic activity of ADEPs. Recently published X-ray structures yielded conflicting models regarding the conformation adopted by the N-terminal regions in the open state. Here, we use hydrogen/deuterium exchange (HDX) mass spectrometry to obtain complementary insights into the ClpP behavior with and without ADEP1. Ligand binding causes rigidification of the equatorial belt, accompanied by destabilization in the vicinity of the binding clefts. The N-terminal regions undergo rapid deuteration with only minor changes after ADEP1 binding, revealing a lack of stable H-bonding. Our data point to a mechanism where the pore opening mechanism is mediated primarily by changes in the packing of N-terminal nonpolar side chains. We propose that a "hydrophobic plug" causes pore blockage in ligand-free ClpP. ADEP1 binding provides new hydrophobic anchor points that nonpolar N-terminal residues can interact with. In this way, ADEP1 triggers the transition to an open conformation, where nonpolar moieties are clustered around the rim of the pore. This proposed mechanism helps reconcile the conflicting models that had been put forward earlier. © 2013.

  1. Aminoglucósidos: mirada actual desde su historia Aminoglycosides: a present look based on their history

    Directory of Open Access Journals (Sweden)

    Miriam Aliño Santiago

    2007-06-01

    Full Text Available Se refiere la historia, mecanismos de acción y eficacia de los aminoglucósidos en los pacientes pediátricos, así como las limitaciones de su utilidad por el surgimiento de resistencias bacterianas originadas por empleo abusivo. Se presenta la estrategia de administración de monodosis, como alternativa frente al método tradicional de dosis fraccionadas, y también las complicaciones más frecuentes y graves de los aminoglucósidos y su sinergismo con otras familias de antimicrobianos. Y se citan investigaciones realizadas en el país en materia de terapia antibiótica.We referred to history, mechanisms of action and efficacy of aminoglycosides in pediatric patients as well as limitations in their use because of the emergence of bacterial resistance caused by overuse. The one-dose administration strategy as an alternative to the traditional methods of fractioned doses, the most frequent and serious complictions of aminoglycosides and their sinergism with other antimicrobial families were presented. We quoted research studies on antibiotic therapy made in the country.

  2. Detection of antibiotic-resistant bacteria endowed with antimicrobial activity from a freshwater lake and their phylogenetic affiliation

    Directory of Open Access Journals (Sweden)

    Zothanpuia

    2016-06-01

    Full Text Available Antimicrobial resistance poses a serious challenge to global public health. In this study, fifty bacterial strains were isolated from the sediments of a freshwater lake and were screened for antibiotic resistance. Out of fifty isolates, thirty-three isolates showed resistance against at least two of the selected antibiotics. Analysis of 16S rDNA sequencing revealed that the isolates belonged to ten different genera, namely Staphylococcus(n = 8, Bacillus(n = 7, Lysinibacillus(n = 4, Achromobacter(n=3, bacterium(n = 3, Methylobacterium(n = 2, Bosea(n = 2, Aneurinibacillus(n = 2, Azospirillum(n = 1, Novosphingobium(n = 1. Enterobacterial repetitive intergenic consensus (ERIC and BOX-PCR markers were used to study the genetic relatedness among the antibiotic resistant isolates. Further, the isolates were screened for their antimicrobial activity against bacterial pathogens viz., Staphylococcus aureus(MTCC-96, Pseudomonas aeruginosa(MTCC-2453 and Escherichia coli(MTCC-739, and pathogenic fungi viz., Fusarium proliferatum (MTCC-286, Fusarium oxysporum (CABI-293942 and Fusarium oxy. ciceri (MTCC-2791. In addition, biosynthetic genes (polyketide synthase II (PKS-II and non-ribosomal peptide synthetase (NRPS were detected in six and seven isolates, respectively. This is the first report for the multifunctional analysis of the bacterial isolates from a wetland with biosynthetic potential, which could serve as potential source of useful biologically active metabolites.

  3. In vitro determination of the antibiotic susceptibility of biofilm-forming Pseudomonas aeruginosa and Staphylococcus aureus: possible role of proteolytic activity and membrane lipopolysaccharide.

    Science.gov (United States)

    Masadeh, Majed M; Mhaidat, Nizar M; Alzoubi, Karem H; Hussein, Emad I; Al-Trad, Esra'a I

    2013-01-01

    We carried out a comprehensive overview of inhibitory effects of selected antibiotics on planktonic and biofilm cells of Staphylococcus aureus (ATCC 29213) and Pseudomonas aeruginosa (ATCC 27853) strains. The possible involvement of protease activity and the lipopolysaccharide (LPS) profile of P. aeruginosa were also analyzed. Biofilm cells of both strains were more resistant to antibiotics than their planktonic counterparts. Protease activity was increased in both strains in the biofilm forms. Challenge with sublethal doses of antibiotics also increased proteolytic activity of biofilm cells. Additionally, the LPS profile of P. aeruginosa showed pattern alterations of the biofilm that can contribute to biofilm resistance and survival. These observations provide evidence for the involvement of bacterial proteolytic activity and LPS profile in the resistance of biofilm bacteria to antibiotics compared to their planktonic counterparts.

  4. Antibiotic radioprotection of mice exposed to supralethal whole-body irradiation independent of antibacterial activity

    International Nuclear Information System (INIS)

    Mastromarino, A.; Wilson, R.

    1976-01-01

    Oral administration of streptomycin, kanamycin, neomycin, or gentamicin to specific pathogen-free C57 x Af mice in their drinking water (4 mg/ml) for 2 weeks before supralethal whole-body irradiation very significantly prolonged their mean survival times (8.2 to 8.9 days vs 6.9 for controls) to values which exceed those reported for germ-free mice (7.3 days). The total fecal concentrations of aerobes and anaerobes were reduced by kanamycin, neomycin, and gentamicin. Streptomycin reduced the anaerobes significantly, but not the aerobes. Unlike germ-free mice, these antibiotic-treated mice did excrete free bile acids, products of bacterial action. Oral antibiotic treatment was ineffective in altering the transit time of the intestinal mucosal cells. Previously reported studies had indicated a correlation between decreased transit time and increased survival after irradiation. No significant correlation between mean survival time after irradiation and mucosal transit time was observed. The data demonstrate that certain antibiotics alter the character of the intestinal bacterial flora and increase protection against supralethal doses of whole-body irradiation. It is concluded that the mechanisms of radioresistance in antibiotic-treated mice and germ-free mice are different and that in both groups radioresistance is the result of more than elimination of postirradiation infection

  5. A Classroom Demonstration of Garlic Extract and Conventional Antibiotics' Antimicrobial Activity

    Science.gov (United States)

    Ekunsanmi, Toye J.

    2005-01-01

    The Kirby-Bauer method is regularly used to test bacterial susceptibility to antibiotics, and is often employed in the classroom for teaching this concept. In this exercise, additional materials and instructions were given to students for the preparation of garlic extract and loading on blank BBL paper discs. They were further instructed to test…

  6. The Influence of Efflux Pump Inhibitors on the Activity of Non-Antibiotic NSAIDS against Gram-Negative Rods.

    Directory of Open Access Journals (Sweden)

    Agnieszka E Laudy

    Full Text Available Most patients with bacterial infections suffer from fever and various pains that require complex treatments with antibiotics, antipyretics, and analgaesics. The most common drugs used to relieve these symptoms are non-steroidal anti-inflammatory drugs (NSAIDs, which are not typically considered antibiotics. Here, we investigate the effects of NSAIDs on bacterial susceptibility to antibiotics and the modulation of bacterial efflux pumps.The activity of 12 NSAID active substances, paracetamol (acetaminophen, and eight relevant medicinal products was analyzed with or without pump inhibitors against 89 strains of Gram-negative rods by determining the MICs. Furthermore, the effects of NSAIDs on the susceptibility of clinical strains to antimicrobial agents with or without PAβN (Phe-Arg-β-naphtylamide were measured.The MICs of diclofenac, mefenamic acid, ibuprofen, and naproxen, in the presence of PAβN, were significantly (≥4-fold reduced, decreasing to 25-1600 mg/L, against the majority of the studied strains. In the case of acetylsalicylic acid only for 5 and 7 out of 12 strains of P. mirabilis and E. coli, respectively, a 4-fold increase in susceptibility in the presence of PAβN was observed. The presence of Aspirin resulted in a 4-fold increase in the MIC of ofloxacin against only two strains of E. coli among 48 tested clinical strains, which included species such as E. coli, K. pneumoniae, P. aeruginosa, and S. maltophilia. Besides, the medicinal products containing the following NSAIDs, diclofenac, mefenamic acid, ibuprofen, and naproxen, did not cause the decrease of clinical strains' susceptibility to antibiotics.The effects of PAβN on the susceptibility of bacteria to NSAIDs indicate that some NSAIDs are substrates for efflux pumps in Gram-negative rods. Morever, Aspirin probably induced efflux-mediated resistance to fluoroquinolones in a few E. coli strains.

  7. Distinct effects of struvite and biochar amendment on the class 1 integron antibiotic resistance gene cassettes in phyllosphere and rhizosphere.

    Science.gov (United States)

    An, Xin-Li; Chen, Qing-Lin; Zhu, Dong; Su, Jian-Qiang

    2018-03-11

    Struvite recovered from wastewater is promising for recycling phosphorus into soil as fertilizers. However, struvite application may prompt the proliferation of antibiotic resistance in soil and plant. This study examined the impacts of struvite application and biochar amendment on integrons abundance and gene cassette contexts in rhizosphere soil and phyllosphere using quantitative PCR and clone library analysis. Microcosm experiments revealed that class 1 integron was the most prevalent in all samples, with higher concentration and higher relative abundance in rhizosphere than those in phyllosphere. The majority of resistance gene cassettes were associated with genes encoding resistance to aminoglycosides, beta-lactams and chloramphenicols. Struvite application significantly increased the genetic diversity of antibiotic resistance gene cassettes in both rhizosphere and phyllosphere. However, biochar amendment attenuated the increasing effect of struvite application exerting on the class 1 integron antibiotic resistance gene cassette pool in phyllosphere. These findings highlighted human activities to be the source of integron gene cassette pool and raised the possibility of using biochar amendment as an alternative mean for mitigating antibiotic resistance in environments. Copyright © 2018 Elsevier B.V. All rights reserved.

  8. Examination of Potential Anti-Tumor Activity of N-Thiolated b-Lactam Antibiotics in Nude Mice Bearing Human Breast Tumors

    Science.gov (United States)

    2006-08-01

    N-methylthiolated beta-lactams the name "penicillin" in 1928 after his discovery that molds from the Penicillium genus secrete powerful antimicrobial ...carboxyl grouin close pr ximin to tlhectam l initro’gen, which is required for antimicrobial activity . These antibiotics act as bactericidal agents...AD AWARD NUMBER: W81XWH-04-1-0688 TITLE: Examination of Potential Anti-Tumor Activity of N-Thiolated b-Lactam Antibiotics in Nude Mice Bearing Human

  9. Examination pf Potential Anti-Tumor Activity of N-Thiolated B-Lactam Antibiotics in Nude Mice Bearing Human Breast Tumors

    Science.gov (United States)

    2005-08-01

    Penicillium genus secrete powerful antimicrobial compounds, called beta-lactams (10). X-ray crystallography revealed that penicillin is a thiazolidine...to the beta-lactam ring, a carboxyl group in close proximity to the lactam nitrogen, which is required for antimicrobial activity . These antibiotics... Activity of N-Thiolated B-Lactam Antibiotics in Nude Mice Bearing Human Breast Tumors PRINCIPAL INVESTIGATOR: Q. Ping Dou, Ph.D

  10. Intracellular activity of the peptide antibiotic NZ2114: studies with Staphylococcus aureus and human THP-1 monocytes, and comparison with daptomycin and vancomycin

    DEFF Research Database (Denmark)

    Brinch, Karoline Sidelmann; Tulkens, Paul M; Van Bambeke, Francoise

    2010-01-01

    Staphylococcus aureus survives inside eukaryotic cells. Our objective was to assess the activity of NZ2114, a novel peptidic antibiotic, against intracellular S. aureus in comparison with established antistaphylococcal agents acting on the bacterial envelope with a distinct mechanism.......Staphylococcus aureus survives inside eukaryotic cells. Our objective was to assess the activity of NZ2114, a novel peptidic antibiotic, against intracellular S. aureus in comparison with established antistaphylococcal agents acting on the bacterial envelope with a distinct mechanism....

  11. Demographics of antibiotic persistence

    DEFF Research Database (Denmark)

    Kollerova, Silvia; Jouvet, Lionel; Steiner, Ulrich

    Persister cells, cells that can survive antibiotic exposure but lack heritable antibiotic resistance, are assumed to play a crucial role for the evolution of antibiotic resistance. Persistence is a stage associated with reduced metabolic activity. Most previous studies have been done on batch...... cultures, rather than the individual level. Here, we used individual level bacteria data to confirm previous studies in how fast cells switch into a persistence stage, but our results challenge the fundamental idea that persistence comes with major costs of reduced growth (cell elongation) and division due...... even play a more prominent role for the evolution of resistance and failures of medical treatment by antibiotics as currently assumed....

  12. Occurrence of antibiotics in pharmaceutical industrial wastewater, wastewater treatment plant and sea waters in Tunisia.

    Science.gov (United States)

    Tahrani, Leyla; Van Loco, Joris; Ben Mansour, Hedi; Reyns, Tim

    2016-04-01

    Antibiotics are among the most commonly used group of pharmaceuticals in human medicine. They can therefore reach surface and groundwater bodies through different routes, such as wastewater treatment plant effluents, surface runoff, or infiltration of water used for agricultural purposes. It is well known that antibiotics pose a significant risk to environmental and human health, even at low concentrations. The aim of the present study was to evaluate the presence of aminoglycosides and phenicol antibiotics in municipal wastewaters, sea water and pharmaceutical effluents in Tunisia. All analysed water samples contained detectable levels of aminoglycoside and phenicol antibiotics. The highest concentrations in wastewater influents were observed for neomycin and kanamycin B (16.4 ng mL(-1) and 7.5 ng mL(-1), respectively). Chloramphenicol was found in wastewater influents up to 3 ng mL(-1). It was observed that the waste water treatment plants were not efficient in completely removing these antibiotics. Chloramphenicol and florfenicol were found in sea water samples near aquaculture sites at levels up to, respectively, 15.6 ng mL(-1) and 18.4 ng mL(-1). Also aminoglycoside antibiotics were found near aquaculture sites with the highest concentration of 3.4 ng mL(-1) for streptomycin. In pharmaceutical effluents, only gentamycin was found at concentrations up to 19 ng mL(-1) over a sampling period of four months.

  13. Sulfonamide-Based Inhibitors of Aminoglycoside Acetyltransferase Eis Abolish Resistance to Kanamycin in Mycobacterium tuberculosis

    Energy Technology Data Exchange (ETDEWEB)

    Garzan, Atefeh; Willby, Melisa J.; Green, Keith D.; Gajadeera, Chathurada S.; Hou, Caixia; Tsodikov, Oleg V.; Posey, James E.; Garneau-Tsodikova, Sylvie

    2016-12-08

    A two-drug combination therapy where one drug targets an offending cell and the other targets a resistance mechanism to the first drug is a time-tested, yet underexploited approach to combat or prevent drug resistance. By high-throughput screening, we identified a sulfonamide scaffold that served as a pharmacophore to generate inhibitors of Mycobacterium tuberculosis acetyltransferase Eis, whose upregulation causes resistance to the aminoglycoside (AG) antibiotic kanamycin A (KAN) in Mycobacterium tuberculosis. Rational systematic derivatization of this scaffold to maximize Eis inhibition and abolish the Eis-mediated KAN resistance of M. tuberculosis yielded several highly potent agents. A crystal structure of Eis in complex with one of the most potent inhibitors revealed that the inhibitor bound Eis in the AG-binding pocket held by a conformationally malleable region of Eis (residues 28–37) bearing key hydrophobic residues. These Eis inhibitors are promising leads for preclinical development of innovative AG combination therapies against resistant TB.

  14. Antibiotic resistance pattern in uropathogens

    Directory of Open Access Journals (Sweden)

    Gupta V

    2002-01-01

    Full Text Available Uropathogenic strains from inpatient and outpatient departments were studied from April 1997 to March 1999 for their susceptibility profiles. The various isolates were Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Acinetobacter baumanii and Enterococcus faecalis. Antibiotic susceptibility pattern of these isolates revealed that for outpatients, first generation cephalosporins, nitrofurantoin, norfloxacin/ciprofloxacin were effective for treatment of urinary tract infection but for inpatients, parenteral therapy with newer aminoglycosides and third generation cephalosporins need to be advocated as the organisms for nosocomial UTI exhibit a high degree of drug resistance. Trimethoprim and sulphamethoxazole combination was not found to be effective for the treatment of urinary tract infections as all the uropathogens from inpatients and outpatients showed high degree of resistance to co-trimoxazole. Culture and sensitivity of the isolates from urine samples should be done as a routine before advocating the therapy.

  15. Evolution of drug resistance: insight on TEM β-lactamases structure and activity and β-lactam antibiotics.

    Science.gov (United States)

    Pimenta, A C; Fernandes, R; Moreira, I S

    2014-02-01

    Since the discovery of the first penicillin bacterial resistance to β-lactam antibiotics has spread and evolved promoting new resistances to pathogens. The most common mechanism of resistance is the production of β-lactamases that have spread thorough nature and evolve to complex phenotypes like CMT type enzymes. New antibiotics have been introduced in clinical practice, and therefore it becomes necessary a concise summary about their molecular targets, specific use and other properties. β-lactamases are still a major medical concern and they have been extensively studied and described in the scientific literature. Several authors agree that Glu166 should be the general base and Ser70 should perform the nucleophilic attack to the carbon of the carbonyl group of the β-lactam ring. Nevertheless there still is controversy on their catalytic mechanism. TEMs evolve at incredible pace presenting more complex phenotypes due to their tolerance to mutations. These mutations lead to an increasing need of novel, stronger and more specific and stable antibiotics. The present review summarizes key structural, molecular and functional aspects of ESBL, IRT and CMT TEM β-lactamases properties and up to date diagrams of the TEM variants with defined phenotype. The activity and structural characteristics of several available TEMs in the NCBI-PDB are presented, as well as the relation of the various mutated residues and their specific properties and some previously proposed catalytic mechanisms.

  16. Biological Activity of Carbazole Alkaloids and Essential Oil of Murraya koenigii Against Antibiotic Resistant Microbes and Cancer Cell Lines

    Directory of Open Access Journals (Sweden)

    Thilahgavani Nagappan

    2011-11-01

    Full Text Available A total of three carbazole alkaloids and essential oil from the leaves of Murraya koenigii (Rutaceae were obtained and examined for their effects on the growth of five antibiotic resistant pathogenic bacteria and three tumor cell lines (MCF-7, P 388 and Hela. The structures of these carbazoles were elucidated based on spectroscopy data and compared with literature data, hence, were identified as mahanine (1, mahanimbicine (2 and mahanimbine (3. The chemical constituents of the essential oil were identified using Gas Chromatography-Mass Spectroscopy (GCMS. These compounds exhibited potent inhibition against antibiotic resistant bacteria such as Staphylococcus aureus (210P JTU, Psedomonas aeruginosa (ATCC 25619, Klebsiella pneumonia (SR1-TU, Escherchia coli (NI23 JTU and Streptococcus pneumoniae (SR16677-PRSP with significant minimum inhibition concentration (MIC values (25.0–175.0 mg/mL and minimum bacteriacidal concentrations (MBC (100.0–500.0 mg/mL. The isolated compounds showed significant antitumor activity against MCF-7, Hela and P388 cell lines. Mahanimbine (3 and essential oil in particular showed potent antibacteria and cytotoxic effect with dose dependent trends (≤5.0 μg/mL. The findings from this investigation are the first report of carbazole alkaloids’ potential against antibiotic resistant clinical bacteria, MCF-7 and P388 cell lines.

  17. Synthesis and evaluation of hetero- and homodimers of ribosome-targeting antibiotics: antimicrobial activity, in vitro inhibition of translation, and drug resistance.

    Science.gov (United States)

    Berkov-Zrihen, Yifat; Green, Keith D; Labby, Kristin J; Feldman, Mark; Garneau-Tsodikova, Sylvie; Fridman, Micha

    2013-07-11

    In this study, we describe the synthesis of a full set of homo- and heterodimers of three intact structures of different ribosome-targeting antibiotics: tobramycin, clindamycin, and chloramphenicol. Several aspects of the biological activity of the dimeric structures were evaluated including antimicrobial activity, inhibition of in vitro bacterial protein translation, and the effect of dimerization on the action of several bacterial resistance mechanisms that deactivate tobramycin and chloramphenicol. This study demonstrates that covalently linking two identical or different ribosome-targeting antibiotics may lead to (i) a broader spectrum of antimicrobial activity, (ii) improved inhibition of bacterial translation properties compared to that of the parent antibiotics, and (iii) reduction in the efficacy of some drug-modifying enzymes that confer high levels of resistance to the parent antibiotics from which the dimers were derived.

  18. In-feed antibiotic effects on the swine intestinal microbiome

    Science.gov (United States)

    Looft, Torey; Johnson, Timothy A.; Allen, Heather K.; Bayles, Darrell O.; Alt, David P.; Stedtfeld, Robert D.; Sul, Woo Jun; Stedtfeld, Tiffany M.; Chai, Benli; Cole, James R.; Hashsham, Syed A.; Tiedje, James M.; Stanton, Thad B.

    2012-01-01

    Antibiotics have been administered to agricultural animals for disease treatment, disease prevention, and growth promotion for over 50 y. The impact of such antibiotic use on the treatment of human diseases is hotly debated. We raised pigs in a highly controlled environment, with one portion of the littermates receiving a diet containing performance-enhancing antibiotics [chlortetracycline, sulfamethazine, and penicillin (known as ASP250)] and the other portion receiving the same diet but without the antibiotics. We used phylogenetic, metagenomic, and quantitative PCR-based approaches to address the impact of antibiotics on the swine gut microbiota. Bacterial phylotypes shifted after 14 d of antibiotic treatment, with the medicated pigs showing an increase in Proteobacteria (1–11%) compared with nonmedicated pigs at the same time point. This shift was driven by an increase in Escherichia coli populations. Analysis of the metagenomes showed that microbial functional genes relating to energy production and conversion were increased in the antibiotic-fed pigs. The results also indicate that antibiotic resistance genes increased in abundance and diversity in the medicated swine microbiome despite a high background of resistance genes in nonmedicated swine. Some enriched genes, such as aminoglycoside O-phosphotransferases, confer resistance to antibiotics that were not administered in this study, demonstrating the potential for indirect selection of resistance to classes of antibiotics not fed. The collateral effects of feeding subtherapeutic doses of antibiotics to agricultural animals are apparent and must be considered in cost-benefit analyses. PMID:22307632

  19. Comparison of bacteriostatic and bactericidal activity of 13 essential oils against strains with varying sensitivity to antibiotics.

    Science.gov (United States)

    Mayaud, L; Carricajo, A; Zhiri, A; Aubert, G

    2008-09-01

    To compare the bacteriostatic and bactericidal activity of 13 chemotyped essential oils (EO) on 65 bacteria with varying sensitivity to antibiotics. Fifty-five bacterial strains were tested with two methods used for evaluation of antimicrobial activity (CLSI recommendations): the agar dilution method and the time-killing curve method. EO containing aldehydes (Cinnamomum verum bark and Cymbopogon citratus), phenols (Origanum compactum, Trachyspermum ammi, Thymus satureioides, Eugenia caryophyllus and Cinnamomum verum leaf) showed the highest antimicrobial activity with minimum inhibitory concentration (MIC) or = 10% (v/v). Against P. aeruginosa, only C. verum bark and O. compactum presented MIC < or =2% (v/v). Cinnamomum verum bark, O. compactum, T. satureioides, C. verum leaf and M. alternifolia were bactericidal against Staphylococcus aureus and Escherichia coli at concentrations ranging from to 0.31% to 10% (v/v) after 1 h of contact. Cinnamomum verum bark and O. compactum were bactericidal against P. aeruginosa within 5 min at concentrations <2% (v/v). Cinnamomum verum bark had the highest antimicrobial activity, particularly against resistant strains. Bacteriostatic and bactericidal activity of EO on nosocomial antibiotic-resistant strains.

  20. Hair cell regeneration in the bullfrog vestibular otolith organs following aminoglycoside toxicity

    Science.gov (United States)

    Baird, Richard A.; Torres, M. A.; Schuff, N. R.

    1994-01-01

    Adult bullfrogs were given single intraotic injections of the aminoglycoside antibiotic gentamicin sulfate and sacrificed at postinjection times ranging from 0.5 to 9 days. The saccular and utricular maculae of normal and injected animals were examined in wholemount and cross-section. Intraotic 200 (mu) M gentamicin concentrations resulted in the uniform destruction of the hair bundles and, at later times, the cell bodies of saccular hair cells. In the utriculus, striolar hair cells were selectively damaged while extrastriolar hair cells were relatively unaffected. Regenerating hair cells, identified in sectioned material by their small cell bodies and short, well-formed hair bundles, were seen in the saccular and utricular maculae as early as 24-48 h postinjection. Immature versions of mature hair cell types in both otolith organs were recognized by the presence of absence of a bulbed kinocilia and the relative lengths of their kinocilia and longest sterocilia. Utricular hair cell types with kinocilia longer than their longest stereocilia were observed at earlier times than hair cell types with shorter kinocilia. In the same sacculus, the hair bundles of gentamicin-treated animals, even at 9 days postinjection, were significantly smaller than those of normal animals. The hair bundles of utricular hair cells, on the other hand, reached full maturity within the same time period.

  1. Pure tone audiograms and possible aminoglycoside-induced hearing loss in belugas (Delphinapterus leucas)

    Science.gov (United States)

    Finneran, James J.; Carder, Donald A.; Dear, Randall; Belting, Traci; McBain, Jim; Dalton, Les; Ridgway, Sam H.

    2005-06-01

    A behavioral response paradigm was used to measure pure-tone hearing sensitivities in two belugas (Delphinapterus leucas). Tests were conducted over a 20-month period at the Point Defiance Zoo and Aquarium, in Tacoma, WA. Subjects were two males, aged 8-10 and 9-11 during the course of the study. Subjects were born in an oceanarium and had been housed together for all of their lives. Hearing thresholds were measured using a modified up/down staircase procedure and acoustic response paradigm where subjects were trained to produce audible responses to test tones and to remain quiet otherwise. Test frequencies ranged from approximately 2 to 130 kHz. Best sensitivities ranged from approximately 40 to 50 dB re 1 μPa at 50-80 kHz and 30-35 kHz for the two subjects. Although both subjects possessed traditional ``U-shaped'' mammalian audiograms, one subject exhibited significant high-frequency hearing loss above 37 kHz compared to previously published data for belugas. Hearing loss in this subject was estimated to approach 90 dB for frequencies above 50 kHz. Similar ages, ancestry, and environmental conditions between subjects, but a history of ototoxic drug administration in only one subject, suggest that the observed hearing loss was a result of the aminoglycoside antibiotic amikacin. .

  2. Antibiotic Agents

    Science.gov (United States)

    ... Superbugs and Drugs" Home | Contact Us General Background: Antibiotic Agents What is an antibacterial and how are ... with the growth and reproduction of bacteria. While antibiotics and antibacterials both attack bacteria, these terms have ...

  3. Polyprenols of Ginkgo biloba Enhance Antibacterial Activity of Five Classes of Antibiotics

    OpenAIRE

    Tao, Ran; Wang, Chengzhang; Ye, Jianzhong; Zhou, Hao; Chen, Hongxia

    2016-01-01

    Polyprenol (GBP) from Ginkgo biloba Leaves (GBL) is an important lipid with many bioactive effects. The effect of GBP on antibacterial properties of five antibiotics belonging to different classes was through analysis of inhibition halos, MIC, and FIC index. And we studied the time-killing curves and Ca2+ mobilization assay in Staphylococcus aureus cells treated with GBP microemulsion and gentamicin sulfate under MIC/2 conditions. These results showed that the GBP microemulsion (average diame...

  4. Antibiotic treatment and dose-response of bacterial activity associated with flatfish eggs

    OpenAIRE

    Mangor-Jensen, Anders; Jelmert, Anders

    1987-01-01

    Newly stripped and fertilized eggs from Plaice (Pleuronectes platessa) and Atlantic Halibut (Hipppoglossus hippoglossus) were incubated in 34 ppt sea water. 150 eggs (Plaice), 30 eggs (Halibut) or 20 glass beads were incubated in 30 ml seawater in light at 5.5°C. The antibiotics Oxytetracycline (-HCl) and Flumiquil were added to end concentration ranges 0 - 105 ppm and 0 - 60 ppm, respectively. With a method modified from Somville and Billen (1983) it was possibl...

  5. [Antibiotic susceptibility of community-acquired strains ofstaphylococcus aureus in Nouakchott Region (Mauritania)].

    Science.gov (United States)

    Salem, Mohamed Lemine Ould; Ghaber, Sidi Mohamed; Baba, Sidi El Wafi Ould; Maouloud, Mohamed Mahmoud Ould

    2016-01-01

    Staphilococcus aureus is a leading pathogen for humans causing a variety of infections such as skin, urinary tract and lung infections as well as sepsis. This study aims to evaluate the susceptibility of community-acquired strains of Staphylococcus aureus, isolated from various pathological products, compared with major antibiotics used in Nouakchott Region (Mauritania). We conducted a retrospective study of 281 strains of Staphylococcus aureus strains isolated from various pathological products from non-hospitalized patients in the National referral hospital laboratory and in two private laboratories in the city of Nouakchott between January 2014 and August 2015. Antibiotic sensitivity was determined by disk diffusion method using agar containing Mueller-Hinton medium according to CA-SFM's recommendations. The resistance rate to penicillin G was high (96-100%). Community-acquired MRSA rate was between 25 and 26% in suppurations, 34.3% in urine cultures and 28% in sperm cultures. Macrolide -Lincosamyne-streptogramins (MLS) resistance, giving rise to the phenotype MLSb inducible, was found in 6% of urinary strains and 27% of strains isolated from suppurations. The activity of aminoglycosides was variable, amikacin was active against all strains. Cotrimoxazole activity was low (77% had resistance) and no vancomycin resistance was reported. The activity of penicillin G against Staphylococcus aureusstrains isolated in Nouakchott region is almost zero and community-acquired MRSA rate is high, accounting for 34%. This could be explained by uncontrolled use of these molecules in our country.

  6. Aminoglycoside-derived amphiphilic nanoparticles for molecular delivery.

    Science.gov (United States)

    Miryala, Bhavani; Godeshala, Sudhakar; Grandhi, Taraka Sai Pavan; Christensen, Matthew D; Tian, Yanqing; Rege, Kaushal

    2016-10-01

    The development of effective drug carriers can lead to improved outcomes in a variety of disease conditions. Aminoglycosides have been used as antibacterial therapeutics, and are attractive as monomers for the development of polymeric materials in various applications. Here, we describe the development of novel aminoglycoside-derived amphiphilic nanoparticles for drug delivery, with an eye towards ablation of cancer cells. The aminoglycoside paromomycin was first cross-linked with resorcinol diglycidyl ether leading to the formation of a poly (amino ether), PAE. PAE molecules were further derivatized with methoxy-terminated poly(ethylene glycol) or mPEG resulting in the formation of mPEG-PAE polymer, which self-assembled to form nanoparticles. Formation of the mPEG-PAE amphiphile was characterized using (1)H NMR, (13)C NMR, gel permeation chromatography (GPC) and FTIR spectroscopy. Self-assembly of the polymer into nanoparticles was characterized using dynamic light scattering, zeta potential analyses, atomic force microscopy (AFM) and the pyrene fluorescence assay. mPEG-PAE nanoparticles were able to carry significant amounts of doxorubicin (DOX), presumably by means of hydrophobic interactions between the drug and the core. Cell-based studies indicated that mPEG-PAE nanoparticles, loaded with doxorubicin, were able to induce significant loss in viabilities of PC3 human prostate cancer, MDA-MB-231 human breast cancer, and MB49 murine bladder cancer cells; empty nanoparticles resulted in negligible losses of cell viability under the conditions investigated. Taken together, our results indicate that the mPEG-PAE nanoparticle platform is attractive for drug delivery in different applications, including cancer. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Rubeomycin, a new anthracycline antibiotic complex. I. Taxonomy of producing organism, isolation, characterization and biological activities of rubeomycin A, A1, B and B1.

    Science.gov (United States)

    Ogawa, Y; Sugi, H; Fujikawa, N; Mori, H

    1981-08-01

    A new antibiotic complex has been obtained from the cultures of an actinomycete, strain FA-1180, isolated from a soil sample collected at lake side of Biwa in Japan. On the basis of taxonomic studies the producing microorganism is designated as Actinomadura roseoviolacea var. biwakoensis nov. var. The antibiotic complex belongs to the class of anthracycline glycoside antibiotics. All components form deep red fine needles on crystallization; components are named rubeomycin A, A1, B and B1. These components exhibit activity against Gram-positive bacteria as well as Yoshida sarcoma cell in vitro. These components are also effective on P388 leukemia.

  8. Improving antibiotic use in daily hospital practice : The antibiotic checklist

    NARCIS (Netherlands)

    van Daalen, F.V.

    2018-01-01

    Better use of current antibiotic agents is necessary to help control antimicrobial resistance (AMR). Antibiotic stewardship programs (ASPs) are introduced to coordinate activities to measure and improve appropriate antibiotic use in daily hospital practice. This thesis shows how the introduction of

  9. Do piperacillin/tazobactam and other antibiotics with inhibitory activity against Clostridium difficile reduce the risk for acquisition of C. difficile colonization?

    Science.gov (United States)

    Kundrapu, Sirisha; Sunkesula, Venkata C K; Jury, Lucy A; Cadnum, Jennifer L; Nerandzic, Michelle M; Musuuza, Jackson S; Sethi, Ajay K; Donskey, Curtis J

    2016-04-18

    Systemic antibiotics vary widely in in vitro activity against Clostridium difficile. Some agents with activity against C. difficile (e.g., piperacillin/tazobactam) inhibit establishment of colonization in mice. We tested the hypothesis that piperacillin/tazobactam and other agents with activity against C. difficile achieve sufficient concentrations in the intestinal tract to inhibit colonization in patients. Point-prevalence culture surveys were conducted to compare the frequency of asymptomatic rectal carriage of toxigenic C. difficile among patients receiving piperacillin/tazobactam or other inhibitory antibiotics (e.g. ampicillin, linezolid, carbapenems) versus antibiotics lacking activity against C. difficile (e.g., cephalosporins, ciprofloxacin). For a subset of patients, in vitro inhibition of C. difficile (defined as a reduction in concentration after inoculation of vegetative C. difficile into fresh stool suspensions) was compared among antibiotic treatment groups. Of 250 patients, 32 (13 %) were asymptomatic carriers of C. difficile. In comparison to patients receiving non-inhibitory antibiotics or prior antibiotics within 90 days, patients currently receiving piperacillin/tazobactam were less likely to be asymptomatic carriers (1/36, 3 versus 7/36, 19 and 15/69, 22 %, respectively; P = 0.024) and more likely to have fecal suspensions with in vitro inhibitory activity against C. difficile (20/28, 71 versus 3/11, 27 and 4/26, 15 %; P = 0.03). Patients receiving other inhibitory antibiotics were not less likely to be asymptomatic carriers than those receiving non-inhibitory antibiotics. Our findings suggest that piperacillin/tazobactam achieves sufficient concentrations in the intestinal tract to inhibit C. difficile colonization during therapy.

  10. Hearing loss and nephrotoxicity treatment in patients with in long-term aminoglycoside tuberculosis

    NARCIS (Netherlands)

    van Altena, R

    OBJECTIVE: To investigate the ototoxic and nephrotoxic effects of long-term use of aminoglycosides. DESIGN: Patients treated for tuberculosis with aminoglycosides were evaluated for hearing loss and nephrotoxicity for a minimum of 14 days. RESULTS: Hearing loss of 15 decibels (dB) at two or more

  11. In Vitro antibacterial and antibiotic-potentiation activities of four edible plants against multidrug-resistant gram-negative species

    Science.gov (United States)

    2013-01-01

    Background The present study was designed to investigate the antibacterial activities of the methanol extracts of four Cameroonian edible plants, locally used to treat microbial infections, and their synergistic effects with antibiotics against a panel of twenty nine Gram-negative bacteria including Multi-drug resistant (MDR) phenotypes expressing active efflux pumps. Methods The broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of the extracts [alone and in the presence of the efflux pumps inhibitor (EPI) Phenylalanine-Arginine β-Naphtylamide (PAβN)], and those of antibiotics in association with the two of the most active ones, Piper nigrum and Telfairia occidentalis. The preliminary phytochemical screening of the extracts was conducted according to the standard phytochemical methods. Results Phytochemical analysis showed the presence of alkaloids and flavonoids in all studied extracts. Other chemical classes of secondary metabolites were selectively present in the extracts. The results of the MIC determination indicated that the crude extracts from P. nigrum and V. amygdalina were able to inhibit the growth of all the twenty nine studied bacteria within a concentration range of 32 to 1024 μg/mL. At a similar concentration range (32 to 1024 μg/mL) the extract from T. occidentalis inhibited the growth of 93.1% of the tested microorganisms. At MIC/2 and MIC/5, synergistic effects were noted between the extracts from P. nigrum and T. occidentalis and seven of the tested antibiotics on more than 70% of the tested bacteria. Conclusion The overall results of the present study provide information for the possible use of the studied edible plants extracts in the control of bacterial infections including MDR phenotypes. PMID:23885762

  12. Trends in antibiotic resistance in bacterial keratitis isolates from South India.

    Science.gov (United States)

    Lalitha, Prajna; Manoharan, Geetha; Karpagam, Rajaram; Prajna, Namperumalsamy V; Srinivasan, Muthiah; Mascarenhas, Jeena; Das, Manoranjan; Porco, Travis C; Lietman, Thomas M; Cevallos, Vicky; Keenan, Jeremy D

    2017-02-01

    To report trends in antibiotic resistance in cases of bacterial keratitis from a large eye hospital in South India. In this retrospective cross-sectional study, the microbiology laboratory records of patients with infectious keratitis diagnosed at an eye hospital in South India from 2002 to 2013 were reviewed to determine the proportion with antibiotic non-susceptibility. 3685 bacterial isolates had susceptibility testing performed over the 12-year period. The two most common organisms with resistance were Streptococcus pneumoniae (n=1204) and Pseudomonas aeruginosa (n=894). Antibiotic non-susceptibility was generally uncommon for these two organisms and no significant trends were detected over the course of the study. In contrast, Staphylococcus aureus (N=211) isolates demonstrated a significant increase in fluoroquinolone non-susceptibility over the 12-year study period. This coincided with a significant increase in methicillin-resistant S. aureus (MRSA) during the study period, though the increase in fluoroquinolone resistance was likewise seen in methicillin-sensitive S. aureus (MSSA). For example, ofloxacin resistance in MSSA increased from 11.1% in 2002 to 66.7% in 2013 (p=0.002). No trends were apparent for the aminoglycosides, cefazolin or vancomycin, for which in vitro non-susceptibility generally appeared to be low. Resistance to antibiotics was generally stable for infectious keratitis isolates from a large eye hospital in South India, except for S. aureus, which experienced a significant increase in fluoroquinolone resistance from 2002 to 2013. Fluoroquinolone antibiotics currently have poor in vitro activity against both MRSA and MSSA in South India and are therefore not the ideal therapy for Staphylococcal corneal ulcers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  13. Thiophene-degrading Escherichia coli mutants possess sulfone oxidase activity and show altered resistance to sulfur-containing antibiotics

    Energy Technology Data Exchange (ETDEWEB)

    Juhl, M.J.; Clark, D.P. (Southern Illinois Univ., Carbondale (USA))

    1990-10-01

    The authors have previously isolated mutants of Escherichia coli which show increased oxidation of heterocyclic furan and thiophene substrates. They have now found that strains carrying the thdA mutation express a novel enzyme activity which oxidizes a variety of substrates containing a sulfone (e.g., ethyl sulfone) were oxidized. The thdA mutants were more resistant than wild-type strains to aromatic sulfone antibiotics such as dapsone. In contrast they showed increased susceptibility to thiolutin, a cyclic antibiotic containing sulfur at the sulfide level of oxidation. Several new thdA mutant alleles were isolated by selecting for increased oxidation of various aliphatic sulfur compounds. These new thdA mutants showed similar sulfone oxidase activity and the same map location (at 10.7 min) as the original thdA1 mutation. The constitutive fadR mutation was required for the phenotypic expression of thdA-mediated oxidation of sulfur compounds. However, the thdA-directed expression of sulfone oxidase activity was not fadR dependent. The thdC and thdD mutations probably protect against the toxicity of thiophene derivatives rather than conferring improved metabolic capability.

  14. Biogenic nanoparticles bearing antibacterial activity and their synergistic effect with broad spectrum antibiotics: Emerging strategy to combat drug

    Directory of Open Access Journals (Sweden)

    Syed Baker

    2017-01-01

    Full Text Available The present study emphasizes on synthesis of bimetallic silver–gold nanoparticles from cell free supernatant of Pseudomonas veronii strain AS41G inhabiting Annona squamosa L. The synthesized nanoparticles were characterized using hyphenated techniques with UV–Visible spectra ascertained absorbance peak between 400 and 800 nm. Possible interaction of biomolecules in mediating and stabilization of nanoparticles was depicted with Fourier transform infrared spectroscopy (FTIR. X-ray diffraction (XRD displayed Bragg’s peak conferring the 100, 111, 200, and 220 facets of the face centered cubic symmetry of nanoparticles suggesting that these nanoparticles were crystalline in nature. Size and shape of the nanoparticles were determined using Transmission electron microscopy (TEM microgram with size ranging from 5 to 50 nm forming myriad shapes. Antibacterial activity of nanoparticles against significant human pathogens was conferred with well diffusion assay and its synergistic effect with standard antibiotics revealed 87.5% fold increased activity with antibiotic “bacitracin” against bacitracin resistant strains Bacillus subtilis, Escherichia coli and Klebsiella pneumoniae followed by kanamycin with 18.5%, gentamicin with 11.15%, streptomycin with 10%, erythromycin with 9.7% and chloramphenicol with 9.4%. Thus the study concludes with biogenic and ecofriendly route for synthesizing nanoparticles with antibacterial activity against drug resistant pathogens and attributes growing interest on endophytes as an emerging source for synthesis of nanoparticles.

  15. Synthesis, optimization, and characterization of silver nanoparticles from Acinetobacter calcoaceticus and their enhanced antibacterial activity when combined with antibiotics

    Directory of Open Access Journals (Sweden)

    Singh R

    2013-11-01

    Full Text Available Richa Singh,1 Priyanka Wagh,1 Sweety Wadhwani,1 Sharvari Gaidhani,2 Avinash Kumbhar,3 Jayesh Bellare,4 Balu Ananda Chopade1 1Department of Microbiology, University of Pune, Pune, Maharashtra, India; 2Institute of Bioinformatics and Biotechnology, University of Pune, Pune, Maharashtra, India; 3Department of Chemistry, University of Pune, Pune, Maharashtra, India; 4Department of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai, Maharashtra, India Background: The development of nontoxic methods of synthesizing nanoparticles is a major step in nanotechnology to allow their application in nanomedicine. The present study aims to biosynthesize silver nanoparticles (AgNPs using a cell-free extract of Acinetobacter spp. and evaluate their antibacterial activity. Methods: Eighteen strains of Acinetobacter were screened for AgNP synthesis. AgNPs were characterized using various techniques. Reaction parameters were optimized, and their effect on the morphology of AgNPs was studied. The synergistic potential of AgNPs on 14 antibiotics against seven pathogens was determined by disc-diffusion, broth-microdilution, and minimum bactericidal concentration assays. The efficacy of AgNPs was evaluated as per the minimum inhibitory concentration (MIC breakpoints of the Clinical and Laboratory Standards Institute (CLSI guidelines. Results: Only A. calcoaceticus LRVP54 produced AgNPs within 24 hours. Monodisperse spherical nanoparticles of 8–12 nm were obtained with 0.7 mM silver nitrate at 70°C. During optimization, a blue-shift in ultraviolet-visible spectra was seen. X-ray diffraction data and lattice fringes (d =0.23 nm observed under high-resolution transmission electron microscope confirmed the crystallinity of AgNPs. These AgNPs were found to be more effective against Gram-negative compared with Gram-positive microorganisms. Overall, AgNPs showed the highest synergy with vancomycin in the disc-diffusion assay. For Enterobacter

  16. Electrophoretic deposition of CdS coatings and their photocatalytic activities in the degradation of tetracycline antibiotic

    Energy Technology Data Exchange (ETDEWEB)

    Vázquez, A., E-mail: alejandro.lqi@gmail.com [Universidad Autónoma de Nuevo León, Facultad de Ciencias Químicas, Av. Universidad S/N, San Nicolás de los Garza, 66455 Nuevo León (Mexico); Hernández-Uresti, D.B., E-mail: ing.dianahdz@gmail.com [Universidad Autónoma de Nuevo León, CICFIM–Facultad de Ciencias Físico Matemáticas, Av. Universidad S/N, San Nicolás de los Garza, 66455 Nuevo León (Mexico); Obregón, S. [Universidad Autónoma de Nuevo León, CICFIM–Facultad de Ciencias Físico Matemáticas, Av. Universidad S/N, San Nicolás de los Garza, 66455 Nuevo León (Mexico)

    2016-11-15

    Highlights: • CdS photocatalyst was prepared by electrophoretic deposition. • The CdS coating was used in the photodegradation of antibiotics. • O{sub 2}{sup −} and ·OH radicals were responsible for the degradation of tetracycline. - Abstract: The photocatalytic activities of CdS coatings formed by electrophoretic deposition (EPD) were evaluated through the photodegradation of an antibiotic, tetracycline. First, CdS nanoparticles were synthesized under microwave irradiation of aqueous solutions containing the cadmium and sulfur precursors at stoichiometric amounts and by using trisodium citrate as stabilizer. Microwave irradiation was carried out in a conventional microwave oven at 2.45 GHz and 1650 W of nominal power, for 60 s. The CdS nanoparticles were characterized by UV–vis spectrophotometry, photoluminescence and X-ray diffraction. Electrophoretic deposition parameters were 300 mV, 600 mV and 900 mV of applied voltage between aluminum plates separated by 1 cm. The fractal dimensions of the surfaces were evaluated by atomic force microscopy and correlated to the morphological and topographic characteristics of the coatings. The photocatalytic activity of the CdS coatings was investigated by means the photodegradation of the tetracycline antibiotic under simulated sunlight irradiation. According to the results, the photoactivity of the coatings directly depends on the concentration of the precursors and the applied voltage during the deposition. The material obtained at 600 mV showed the best photocatalytic behavior, probably due to its physical properties, such as optimum load and suitable aggregate size.

  17. Electrophoretic deposition of CdS coatings and their photocatalytic activities in the degradation of tetracycline antibiotic

    International Nuclear Information System (INIS)

    Vázquez, A.; Hernández-Uresti, D.B.; Obregón, S.

    2016-01-01

    Highlights: • CdS photocatalyst was prepared by electrophoretic deposition. • The CdS coating was used in the photodegradation of antibiotics. • O 2 − and ·OH radicals were responsible for the degradation of tetracycline. - Abstract: The photocatalytic activities of CdS coatings formed by electrophoretic deposition (EPD) were evaluated through the photodegradation of an antibiotic, tetracycline. First, CdS nanoparticles were synthesized under microwave irradiation of aqueous solutions containing the cadmium and sulfur precursors at stoichiometric amounts and by using trisodium citrate as stabilizer. Microwave irradiation was carried out in a conventional microwave oven at 2.45 GHz and 1650 W of nominal power, for 60 s. The CdS nanoparticles were characterized by UV–vis spectrophotometry, photoluminescence and X-ray diffraction. Electrophoretic deposition parameters were 300 mV, 600 mV and 900 mV of applied voltage between aluminum plates separated by 1 cm. The fractal dimensions of the surfaces were evaluated by atomic force microscopy and correlated to the morphological and topographic characteristics of the coatings. The photocatalytic activity of the CdS coatings was investigated by means the photodegradation of the tetracycline antibiotic under simulated sunlight irradiation. According to the results, the photoactivity of the coatings directly depends on the concentration of the precursors and the applied voltage during the deposition. The material obtained at 600 mV showed the best photocatalytic behavior, probably due to its physical properties, such as optimum load and suitable aggregate size.

  18. A low-barrier hydrogen bond mediates antibiotic resistance in a noncanonical catalytic triad

    Science.gov (United States)

    2018-01-01

    One group of enzymes that confer resistance to aminoglycoside antibiotics through covalent modification belongs to the GCN5-related N-acetyltransferase (GNAT) superfamily. We show how a unique GNAT subfamily member uses a previously unidentified noncanonical catalytic triad, consisting of a glutamic acid, a histidine, and the antibiotic substrate itself, which acts as a nucleophile and attacks the acetyl donor molecule. Neutron diffraction studies allow for unambiguous identification of a low-barrier hydrogen bond, predicted in canonical catalytic triads to increase basicity of the histidine. This work highlights the role of this unique catalytic triad in mediating antibiotic resistance while providing new insights into the design of the next generation of aminoglycosides. PMID:29632894

  19. Bacteriocin-like inhibitory activities of seven Lactobacillus delbrueckii subsp. bulgaricus strains against antibiotic susceptible and resistant Helicobacter pylori strains.

    Science.gov (United States)

    Boyanova, L; Gergova, G; Markovska, R; Yordanov, D; Mitov, I

    2017-12-01

    The aim of the study was to detect anti-Helicobacter pylori activity of seven Lactobacillus delbrueckii subsp. bulgaricus (GLB) strains by four cell-free supernatant (CFS) types. Activity of non-neutralized and non-heat-treated (CFSs1), non-neutralized and heat-treated (CFSs2), pH neutralized, catalase-treated and non-heat-treated (CFSs3), or neutralized, catalase- and heat-treated (CFSs4) CFSs against 18 H. pylori strains (11 of which with antibiotic resistance) was evaluated. All GLB strains produced bacteriocin-like inhibitory substances (BLISs), the neutralized CFSs of two GLB strains inhibited >81% of test strains and those of four GLB strains were active against >71% of antibiotic resistant strains. Two H. pylori strains were BLIS resistant. The heating did not reduce the CFS activity. Briefly, all GLB strains evaluated produced heat-stable BLISs, although GLB and H. pylori strain susceptibility patterns exhibited differences. Bacteriocin-like inhibitory substance activity can be an advantage for the probiotic choice for H. pylori infection control. In this study, anti-Helicobacter pylori activity of seven Lactobacillus delbrueckii subsp. bulgaricus (GLB) strains was evaluated by four cell-free supernatant (CFS) types. The GLB strains produced heat-stable bacteriocin-like inhibitory substances (BLISs) with a strong anti-H. pylori activity and some neutralized, catalase- and heat-treated CFSs inhibited >83% of the test strains. Bacteriocin-like inhibitory substance production of GLB strains can render them valuable probiotics in the control of H. pylori infection. © 2017 The Society for Applied Microbiology.

  20. Parallel Solution-Phase Synthesis and General Biological Activity of a Uridine Antibiotic Analog Library

    OpenAIRE

    Moukha-chafiq, Omar; Reynolds, Robert C.

    2014-01-01

    A small library of ninety four uridine antibiotic analogs was synthesized, under the Pilot Scale Library (PSL) Program of the NIH Roadmap initiative, from amine 2 and carboxylic acids 33 and 77 in solution-phase fashion. Diverse aldehyde, sulfonyl chloride, and carboxylic acid reactant sets were condensed to 2, leading after acid-mediated hydrolysis, to the targeted compounds 3?32 in good yields and high purity. Similarly, treatment of 33 with diverse amines and sulfonamides gave 34?75. The c...

  1. Coenzyme Q10 protects hair cells against aminoglycoside.

    Directory of Open Access Journals (Sweden)

    Kazuma Sugahara

    Full Text Available It is well known that the production of free radicals is associated with sensory cell death induced by an aminoglycoside. Many researchers have reported that antioxidant reagents protect sensory cells in the inner ear, and coenzyme Q10 (CoQ10 is an antioxidant that is consumed as a health food in many countries. The purpose of this study was to investigate the role of CoQ10 in mammalian vestibular hair cell death induced by aminoglycoside. Cultured utricles of CBA/CaN mice were divided into three groups (control group, neomycin group, and neomycin + CoQ10 group. In the neomycin group, utricles were cultured with neomycin (1 mM to induce hair cell death. In the neomycin + CoQ10 group, utricles were cultured with neomycin and water-soluble CoQ10 (30-0.3 µM. Twenty-four hours after exposure to neomycin, the cultured tissues were fixed, and vestibular hair cells were labeled using an anti-calmodulin antibody. Significantly more hair cells survived in the neomycin + CoQ10 group than in the neomycin group. These data indicate that CoQ10 protects sensory hair cells against neomycin-induced death in the mammalian vestibular epithelium; therefore, CoQ10 may be useful as a protective drug in the inner ear.

  2. [Investigation of molecular mechanisms of aminoglycoside resistance in Salmonella].

    Science.gov (United States)

    Zubritskiĭ, A V; Il'ina, E N; Strel'chenko, S A; Malakhova, M V; Lenev, S V; Skliarov, O D; Panin, A N; Govorun, V M

    2011-01-01

    The spread of aminoglycoside resistance phenotype and respective genetic resistance determinants was evaluated in 243 Salmonella strains isolated within 1948-2010 and stored in the Culture Collection of the Russian State Research Institute for Control, Standardization and Certification of Veterinary Preparations (Moscow). The Salmonella strains showed resistance to streptomycin and gentamicin in 3.7% (n = 9) and 0.8% (n = 2) of the isolates respectively. Intermediate resistance to streptomycin was recorded in 9.9% (n = 24) of the isolates. To detect the genes responsible for the aminoglycoside resistance, primers for aadA1, aadA2, aadB, aphA1, aphA3, sat, strA, strB, aphA, aacC, rmtB, armA and rpsL genes amplification and sequencing were designed. The strains with lower susceptibility to streptomycin harbored aadA1, aadA2, strA, strB resistance genes encoding enzymes for aminoglicoside modification and rpsL mutant allele (K42N, G91D). Genetic mechanisms able to explain the gentamicin resistance development were not detected. Some strains carried genetic markers of streptomycine resistance but had no clinically sufficient resistance to it. In this regard, genetic testing is essential for prevention of drug resistance spreading due to horizontal transfer of genes in microbial population.

  3. In vitro bactericidal activity of Jinghua Weikang Capsule and its individual herb Chenopodium ambrosioides L. against antibiotic-resistant Helicobacter pylori.

    Science.gov (United States)

    Liu, Wei; Liu, Yu; Zhang, Xue-Zhi; Li, Ning; Cheng, Hong

    2013-01-01

    To investigate the bactericidal effects of Jinghua Weikang Capsule and its major component Chenopodium ambrosioides L. on antibiotic-resistant Helicobacter pylori. Four clinical antibiotic-resistant H. pylori strains were isolated and incubated in liquid medium containing Jinghua Weikang Capsule or Chenopodium ambrosioides L. By means of time-kill curve method, the average colony counts and bactericidal rate were calculated at time points of 0, 4, 8 and 24 h after the incubation and the time-kill curves were charted. Both Jinghua Weikang Capsule and Chenopodium ambrosioides L. at a concentration of 0.64 g/L showed obvious bactericidal effect against antibiotic-resistant H. pylori after 4 h of incubation. Jinghua Weikang Capsule and Chenopodium ambrosioides L. are considered to be active against antibiotic-resistant H. pylori in vitro.

  4. Effects of loading concentration, blood and synovial fluid on antibiotic release and anti-biofilm activity of bone cement beads

    OpenAIRE

    Dusane, Devendra H.; Diamond, Scott M.; Knecht, Cory S.; Farrar, Nicholas R.; Peters, Casey W.; Howlin, Robert P.; Swearingen, Matthew C.; Calhoun, Jason H.; Plaut, Roger D.; Nocera, Tanya M.; Granger, Jeffrey F.; Stoodley, Paul

    2017-01-01

    Antibiotic loaded cement beads are commonly used for the treatment of biofilm related orthopaedic periprosthetic infections; however the effects of antibiotic loading and exposure of beads to body fluids on release kinetics are unclear. The purpose of this study was to determine the effects of (i) antibiotic loading density (ii) loading amount (iii) material type and (iv) exposure to body fluids (blood or synovial fluid) on release kinetics and efficacy of antibiotics against planktonic and l...

  5. Antibacterial and antibiotic resistance modulatory activities of leaves and bark extracts of Recinodindron heudelotii (Euphorbiaceae) against multidrug-resistant Gram-negative bacteria.

    Science.gov (United States)

    Fankam, Aimé Gabriel; Kuiate, Jules-Roger; Kuete, Victor

    2017-03-24

    Recinodindron heudelotii (Euphorbiaceae) is a plant used in Africa, particularly in Cameroon to treat various ailments including bacterial infections. In this study, we evaluated the extracts of the leaves (RHL) and bark (RHB) of R. heudelotii for their antibacterial and antibiotic resistance modulating activities against 29 Gram-negative bacteria, including multidrug-resistant (MDR) phenotypes. The broth micro-dilution assay was used to evaluate the antibacterial activity, and the antibiotic resistance modulating effects of the plant extracts. RHL displayed the most important spectrum of activity with minimal inhibitory concentrations (MICs) values ranging from 256 to 1024 μg/mL against 75.86% of the 29 tested bacteria strains while RHB was not active. RHL also showed killing effects with minimal bactericidal concentrations (MBCs) ranging from 256 to 1024 μg/mL. The activities of tetracycline and kanamycin associated with RHL were improved on 88.89% and 77.78% of the tested MDR bacteria, at MIC/2 at MIC/4 respectively, with 2 to 16-folds decreasing of MIC. This suggests the antibiotic resistance modulating effects of these antibiotics. The present study provides data indicating a possible use of the leaves extract of Recinodindron heudelotii alone or in association with common antibiotics in the fight against bacterial infections including those involving MDR bacteria.

  6. Spectrophotometric Determination of Aminoglycoside Antibiotics Based on their Oxidation by Potassium Permanganate

    International Nuclear Information System (INIS)

    El-Didamony, A. M.; Ghoneim, A. K.; Telebany, A. M.; Amin, A. S.

    2006-01-01

    A rapid, simple and sensitive validated spectrophotometric methods have been described for the assay of neomycin and streptomycin either in pure form or in pharmaceutical formulations. The proposed methods were based on the oxidation of the studied drugs by a known excess of potassium permanganate in acidic medium and estimating the unreacted permanganate with amaranth dye (method A), acid orange II (method B), indigocarmine (method C), and methylene blue (method D), in the same acid medium at a suitable λ max =521, 485, 610 and 664 nm, respectively. Beer's law is obeyed in the concentration range of 5-10 and 2-7 mg mL -1 for neomycin and streptomycin, respectively. The apparent molar absorptivity and sandell sensitivity values are in the range 5.47-6.20x10 4 , 2.35-2.91x10 5 L mol -1 cm -1 and 7.57-8.59, 5.01-6.2 ng cm -2 for neomycin and streptomycin, respectively. Different variables affecting the reaction were studied and optimized. The proposed methods were applied successfully to the determination of the examined drugs either in a pure or pharmaceutical dosage forms with good accuracy and precision. No interferences were observed from excipients and the results obtained were in good agreement with those obtained using the official methods

  7. Amplification of vacuole-targeting fungicidal activity of antibacterial antibiotic polymyxin B by allicin, an allyl sulfur compound from garlic.

    Science.gov (United States)

    Ogita, Akira; Nagao, Yasuhiro; Fujita, Ken-Ichi; Tanaka, Toshio

    2007-08-01

    A cationic antibacterial peptide, polymyxin B (PMB), was evaluated as an antifungal antibiotic against various yeasts and filamentous fungi when used in combination with allicin, an allyl sulfur compound from garlic. Allicin was not lethal but could markedly amplify the fungicidal activity of PMB, which was weakly detected with the increase in the plasma membrane permeability in Saccharomyces cerevisiae. Their combined actions caused a dynamic structural damage to the yeast vacuole as judged by the disappearance of its swollen spherical architecture. The vacuole-targeting activity of PMB was similarly amplified in medium with t-butyl hydroperoxide as a substitute for the action of allicin. These findings suggest that the allicin-mediated lipoperoxide production in fungal plasma membrane is the cause of the enhancement in the cellular uptake of PMB as well as its action against the vacuole.

  8. Enhanced removal of sulfonamide antibiotics by KOH-activated anthracite coal: Batch and fixed-bed studies.

    Science.gov (United States)

    Zuo, Linzi; Ai, Jing; Fu, Heyun; Chen, Wei; Zheng, Shourong; Xu, Zhaoyi; Zhu, Dongqiang

    2016-04-01

    The presence of sulfonamide antibiotics in aquatic environments poses potential risks to human health and ecosystems. In the present study, a highly porous activated carbon was prepared by KOH activation of an anthracite coal (Anth-KOH), and its adsorption properties toward two sulfonamides (sulfamethoxazole and sulfapyridine) and three smaller-sized monoaromatics (phenol, 4-nitrophenol and 1,3-dinitrobenzene) were examined in both batch and fixed-bed adsorption experiments to probe the interplay between adsorbate molecular size and adsorbent pore structure. A commercial powder microporous activated carbon (PAC) and a commercial mesoporous carbon (CMK-3) possessing distinct pore properties were included as comparative adsorbents. Among the three adsorbents Anth-KOH exhibited the largest adsorption capacities for all test adsorbates (especially the two sulfonamides) in both batch mode and fixed-bed mode. After being normalized by the adsorbent surface area, the batch adsorption isotherms of sulfonamides on PAC and Anth-KOH were displaced upward relative to the isotherms on CMK-3, likely due to the micropore-filling effect facilitated by the microporosity of adsorbents. In the fixed-bed mode, the surface area-normalized adsorption capacities of Anth-KOH for sulfonamides were close to that of CMK-3, and higher than that of PAC. The irregular, closed micropores of PAC might impede the diffusion of the relatively large-sized sulfonamide molecules and in turn led to lowered fixed-bed adsorption capacities. The overall superior adsorption of sulfonamides on Anth-KOH can be attributed to its large specific surface area (2514 m(2)/g), high pore volume (1.23 cm(3)/g) and large micropore sizes (centered at 2.0 nm). These findings imply that KOH-activated anthracite coal is a promising adsorbent for the removal of sulfonamide antibiotics from aqueous solution. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. New insights into the aquatic photochemistry of fluoroquinolone antibiotics: Direct photodegradation, hydroxyl-radical oxidation, and antibacterial activity changes

    Energy Technology Data Exchange (ETDEWEB)

    Ge, Linke; Na, Guangshui [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Zhang, Siyu [Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016 (China); Li, Kai [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Zhang, Peng, E-mail: pzhang@nmemc.org.cn [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China); Ren, Honglei; Yao, Ziwei [Key Laboratory for Ecological Environment in Coastal Areas (SOA), National Marine Environmental Monitoring Center, Dalian 116023 (China)

    2015-09-15

    The ubiquity and photoreactivity of fluoroquinolone antibiotics (FQs) in surface waters urge new insights into their aqueous photochemical behavior. This study concerns the photochemistry of 6 FQs: ciprofloxacin, danofloxacin, levofloxacin, sarafloxacin, difloxacin and enrofloxacin. Methods were developed to calculate their solar direct photodegradation half-lives (t{sub d,E}) and hydroxyl-radical oxidation half-lives (t{sub ·OH,E}) in sunlit surface waters. The t{sub d,E} values range from 0.56 min to 28.8 min at 45° N latitude, whereas t{sub ·OH,E} ranges from 3.24 h to 33.6 h, suggesting that most FQs tend to undergo fast direct photolysis rather than hydroxyl-radical oxidation in surface waters. However, a case study for levofloxacin and sarafloxacin indicated that the hydroxyl-radical oxidation induced risky photochlorination and resulted in multi-degradation pathways, such as piperazinyl hydroxylation and clearage. Changes in the antibacterial activity of FQs caused by photodegradation in various waters were further examined using Escherichia coli, and it was found that the activity evolution depended on primary photodegradation pathways and products. Primary intermediates with intact FQ nuclei retained significant antibacterial activity. These results are important for assessing the fate and risk of FQs in surface waters. - Highlights: • It is first reported on hydroxyl-radical oxidation of 6 fluoroquinolone antibiotics. • Methods were developed to assess photolysis and oxidation fate in surface waters. • The neutral form reacted faster with hydroxyl radical than protonated forms. • The main oxidation intermediates and transformation pathways were clarified. • The antibacterial activity changes depend on dominant photolysis pathways.

  10. New insights into the aquatic photochemistry of fluoroquinolone antibiotics: Direct photodegradation, hydroxyl-radical oxidation, and antibacterial activity changes

    International Nuclear Information System (INIS)

    Ge, Linke; Na, Guangshui; Zhang, Siyu; Li, Kai; Zhang, Peng; Ren, Honglei; Yao, Ziwei

    2015-01-01

    The ubiquity and photoreactivity of fluoroquinolone antibiotics (FQs) in surface waters urge new insights into their aqueous photochemical behavior. This study concerns the photochemistry of 6 FQs: ciprofloxacin, danofloxacin, levofloxacin, sarafloxacin, difloxacin and enrofloxacin. Methods were developed to calculate their solar direct photodegradation half-lives (t d,E ) and hydroxyl-radical oxidation half-lives (t ·OH,E ) in sunlit surface waters. The t d,E values range from 0.56 min to 28.8 min at 45° N latitude, whereas t ·OH,E ranges from 3.24 h to 33.6 h, suggesting that most FQs tend to undergo fast direct photolysis rather than hydroxyl-radical oxidation in surface waters. However, a case study for levofloxacin and sarafloxacin indicated that the hydroxyl-radical oxidation induced risky photochlorination and resulted in multi-degradation pathways, such as piperazinyl hydroxylation and clearage. Changes in the antibacterial activity of FQs caused by photodegradation in various waters were further examined using Escherichia coli, and it was found that the activity evolution depended on primary photodegradation pathways and products. Primary intermediates with intact FQ nuclei retained significant antibacterial activity. These results are important for assessing the fate and risk of FQs in surface waters. - Highlights: • It is first reported on hydroxyl-radical oxidation of 6 fluoroquinolone antibiotics. • Methods were developed to assess photolysis and oxidation fate in surface waters. • The neutral form reacted faster with hydroxyl radical than protonated forms. • The main oxidation intermediates and transformation pathways were clarified. • The antibacterial activity changes depend on dominant photolysis pathways

  11. In vitro activity of beta-lactam antibiotics to community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA).

    Science.gov (United States)

    Germel, C; Haag, A; Söderquist, B

    2012-04-01

    Community-associated (CA) MRSA often display low MIC values against oxacillin. The in vitro activity of various beta-lactam antibiotics against heterogeneous CA-MRSA (n = 98) isolated in a low endemic area was determined by Etest, and Mueller-Hinton agar (MUHAP) was compared with Mueller-Hinton agar supplemented with 2% NaCl (MUHSP). In general, the CA-MRSA isolates showed higher MIC values for the various beta-lactam antibiotics on MUHSP compared with MUHAP. MIC values for oxacillin ranged from 1 to >256 mg/L on MUHSP. Cephalothin, representing the first generation of cephalosporins, showed MICs from 0.75 to 96 mg/L and the MIC(50) and MIC(90) for cefuroxime, cefotaxime and cefepime, representing the second, third and fourth generations, respectively, were rather high. However, the MIC(50) and MIC(90) for ceftobiprole (fifth generation) were 1.5 and 2 mg/L, respectively, on MUHSP. The MIC(50) and MIC(90) for imipenem were 0.75 and 2 mg/L, respectively, on MUHSP. Only 3/98 (3%) CA-MRSA isolates showed a MIC >4 mg/L. Consequently, low MIC values for imipenem, lower than those of the newly developed fifth generation cephalosporins, were found among CA-MRSA. These findings may be considered for further studies including clinical trials in order to evaluate carbapenems as a potential treatment option for infections caused by CA-MRSA.

  12. Chemistry, Antimicrobial Mechanisms, and Antibiotic Activities of Cinnamaldehyde against Pathogenic Bacteria in Animal Feeds and Human Foods.

    Science.gov (United States)

    Friedman, Mendel

    2017-12-06

    Cinnamaldehyde is a major constituent of cinnamon essential oils produced by aromatic cinnamon plants. This compound has been reported to exhibit antimicrobial properties in vitro in laboratory media and in animal feeds and human foods contaminated with disease-causing bacteria including Bacillus cereus, Campylobacter jejuni, Clostridium perfringens, Escherichia coli, Listeria monocytogenes, and Salmonella enterica. This integrated review surveys and interprets our current knowledge of the chemistry, analysis, safety, mechanism of action, and antibiotic activities of cinnamaldehyde in food animal (cattle, lambs, calves, pigs, poultry) diets and in widely consumed liquid (apple, carrot, tomato, and watermelon juices, milk) and solid foods. Solid foods include various fruits (bayberries, blueberries, raspberries, and strawberries), vegetables (carrots, celery, lettuce, spinach, cucumbers, and tomatoes), meats (beef, ham, pork, and frankfurters), poultry (chickens and turkeys), seafood (oysters and shrimp), bread, cheese, eggs, infant formula, and peanut paste. The described findings are not only of fundamental interest but also have practical implications for food safety, nutrition, and animal and human health. The collated information and suggested research needs will hopefully facilitate and guide further studies needed to optimize the use of cinnamaldehyde alone and in combination with other natural antimicrobials and medicinal antibiotics to help prevent and treat food animal and human diseases.

  13. A Comprehensive Insight into Tetracycline Resistant Bacteria and Antibiotic Resistance Genes in Activated Sludge Using Next-Generation Sequencing

    Science.gov (United States)

    Huang, Kailong; Tang, Junying; Zhang, Xu-Xiang; Xu, Ke; Ren, Hongqiang

    2014-01-01

    In order to comprehensively investigate tetracycline resistance in activated sludge of sewage treatment plants, 454 pyrosequencing and Illumina high-throughput sequencing were used to detect potential tetracycline resistant bacteria (TRB) and antibiotic resistance genes (ARGs) in sludge cultured with different concentrations of tetracycline. Pyrosequencing of 16S rRNA gene revealed that tetracycline treatment greatly affected the bacterial community structure of the sludge. Nine genera consisting of Sulfuritalea, Armatimonas, Prosthecobacter, Hyphomicrobium, Azonexus, Longilinea, Paracoccus, Novosphingobium and Rhodobacter were identified as potential TRB in the sludge. Results of qPCR, molecular cloning and metagenomic analysis consistently indicated that tetracycline treatment could increase both the abundance and diversity of the tet genes, but decreased the occurrence and diversity of non-tetracycline ARG, especially sulfonamide resistance gene sul2. Cluster analysis showed that tetracycline treatment at subinhibitory concentrations (5 mg/L) was found to pose greater effects on the bacterial community composition, which may be responsible for the variations of the ARGs abundance. This study indicated that joint use of 454 pyrosequencing and Illumina high-throughput sequencing can be effectively used to explore ARB and ARGs in the environment, and future studies should include an in-depth investigation of the relationship between microbial community, ARGs and antibiotics in sewage treatment plant (STP) sludge. PMID:24905407

  14. A Comprehensive Insight into Tetracycline Resistant Bacteria and Antibiotic Resistance Genes in Activated Sludge Using Next-Generation Sequencing

    Directory of Open Access Journals (Sweden)

    Kailong Huang

    2014-06-01

    Full Text Available In order to comprehensively investigate tetracycline resistance in activated sludge of sewage treatment plants, 454 pyrosequencing and Illumina high-throughput sequencing were used to detect potential tetracycline resistant bacteria (TRB and antibiotic resistance genes (ARGs in sludge cultured with different concentrations of tetracycline. Pyrosequencing of 16S rRNA gene revealed that tetracycline treatment greatly affected the bacterial community structure of the sludge. Nine genera consisting of Sulfuritalea, Armatimonas, Prosthecobacter, Hyphomicrobium, Azonexus, Longilinea, Paracoccus, Novosphingobium and Rhodobacter were identified as potential TRB in the sludge. Results of qPCR, molecular cloning and metagenomic analysis consistently indicated that tetracycline treatment could increase both the abundance and diversity of the tet genes, but decreased the occurrence and diversity of non-tetracycline ARG, especially sulfonamide resistance gene sul2. Cluster analysis showed that tetracycline treatment at subinhibitory concentrations (5 mg/L was found to pose greater effects on the bacterial community composition, which may be responsible for the variations of the ARGs abundance. This study indicated that joint use of 454 pyrosequencing and Illumina high-throughput sequencing can be effectively used to explore ARB and ARGs in the environment, and future studies should include an in-depth investigation of the relationship between microbial community, ARGs and antibiotics in sewage treatment plant (STP sludge.

  15. A comprehensive insight into tetracycline resistant bacteria and antibiotic resistance genes in activated sludge using next-generation sequencing.

    Science.gov (United States)

    Huang, Kailong; Tang, Junying; Zhang, Xu-Xiang; Xu, Ke; Ren, Hongqiang

    2014-06-05

    In order to comprehensively investigate tetracycline resistance in activated sludge of sewage treatment plants, 454 pyrosequencing and Illumina high-throughput sequencing were used to detect potential tetracycline resistant bacteria (TRB) and antibiotic resistance genes (ARGs) in sludge cultured with different concentrations of tetracycline. Pyrosequencing of 16S rRNA gene revealed that tetracycline treatment greatly affected the bacterial community structure of the sludge. Nine genera consisting of Sulfuritalea, Armatimonas, Prosthecobacter, Hyphomicrobium, Azonexus, Longilinea, Paracoccus, Novosphingobium and Rhodobacter were identified as potential TRB in the sludge. Results of qPCR, molecular cloning and metagenomic analysis consistently indicated that tetracycline treatment could increase both the abundance and diversity of the tet genes, but decreased the occurrence and diversity of non-tetracycline ARG, especially sulfonamide resistance gene sul2. Cluster analysis showed that tetracycline treatment at subinhibitory concentrations (5 mg/L) was found to pose greater effects on the bacterial community composition, which may be responsible for the variations of the ARGs abundance. This study indicated that joint use of 454 pyrosequencing and Illumina high-throughput sequencing can be effectively used to explore ARB and ARGs in the environment, and future studies should include an in-depth investigation of the relationship between microbial community, ARGs and antibiotics in sewage treatment plant (STP) sludge.

  16. Synergistic antibacterial activity of the combination of the alkaloid sanguinarine with EDTA and the antibiotic streptomycin against multidrug resistant bacteria.

    Science.gov (United States)

    Hamoud, Razan; Reichling, Jürgen; Wink, Michael

    2015-02-01

    Drug combinations consisting of the DNA intercalating benzophenanthridine alkaloid sanguinarine, the chelator EDTA with the antibiotic streptomycin were tested against several Gram-positive and Gram-negative bacteria, including multi-resistant clinical isolates. Microdilution, checkerboard and time kill curve methods were used to investigate the antibacterial activity of the individual drugs and the potential synergistic activity of combinations. Sanguinarine demonstrated a strong activity against Gram-positive and Gram-negative bacteria (minimum inhibitory concentrations, MIC = 0.5-128 μg/ml), while streptomycin was active against Gram-negative strains (MIC = 2-128 μg/ml). EDTA showed only bacteriostatic activity. Indifference to synergistic activity was seen in the two-drug combinations sanguinarine + EDTA and sanguinarine + streptomycin (fractional inhibitory concentration index = 0.1-1.5), while the three-drug combination of sanguinarine + EDTA + streptomycin showed synergistic activity against almost all the strains (except methicillin-resistant Staphylococcus aureus), as well as a strong reduction in the effective doses (dose reduction index = 2-16 times) of sanguinarine, EDTA and streptomycin. In time kill studies, a substantial synergistic interaction of the three-drug combination was detected against Escherichia coli and Klebsiella pneumoniae. The combination of drugs, which interfere with different molecular targets, can be an important strategy to combat multidrug resistant bacteria. © 2014 Royal Pharmaceutical Society.

  17. Utilisation of antibiotic therapy in community practice.

    LENUS (Irish Health Repository)

    McGowan, B

    2008-10-01

    The aim of the study was to identify outpatient antibiotic consumption between Jan 2000 and Dec 2005 through analysis of the HSE-Primary Care Reimbursement Services (PCRS) database as part of the Surveillance of Antimicrobial Resistance in Ireland (SARI) project. Total antibiotic consumption on the PCRS scheme between January 2000 and December 2005 expressed in Defined Daily Dose per 1000 PCRS inhabitants per day increased by 26%. The penicillin group represents the highest consumption accounting for approximately 50% of the total outpatient antibiotic use. Total DIDs for this group increased by 25% between 2000 and 2005. Co-amoxiclav and amoxicillin account for 80% of the total consumption of this group of anti-infectives. With the exception of aminoglycosides and sulfonamides which demonstrated a decrease in DID consumption of 47% and 8% respectively, all other groups of anti-infectives had an increase in DID consumption of greater than 25% during the study period. Antibiotic prescribing data is a valuable tool for assessing public health strategies aiming to optimise antibiotic prescribing.

  18. History of Antibiotics Research.

    Science.gov (United States)

    Mohr, Kathrin I

    2016-01-01

    . Whenever a new antibiotic reached the market it did not take long until scientists observed the first resistant germs. Since the marketing of the first antibiotic there is a neck-on-neck race between scientists who discover natural or develop semisynthetic and synthetic bioactive molecules and bacteria, which have developed resistance mechanisms. The emphasis of this chapter is to give an overview of the history of antibiotics research. The situation within the pre-antibiotic era as well as in the early antibiotic era will be described until the Golden Age of Antibiotics will conclude this time travel. The most important antibiotic classes, information about their discovery, activity spectrum, mode of action, resistance mechanisms, and current application will be presented.

  19. Deciphering the details of RNA aminoglycoside interactions: from atomistic models to biotechnological applications

    Energy Technology Data Exchange (ETDEWEB)

    Ilgu, Muslum [Iowa State Univ., Ames, IA (United States)

    2012-01-01

    A detailed study was done of the neomycin-B RNA aptamer for determining its selectivity and binding ability to both neomycin– and kanamycin-class aminoglycosides. A novel method to increase drug concentrations in cells for more efficiently killing is described. To test the method, a bacterial model system was adopted and several small RNA molecules interacting with aminoglycosides were cloned downstream of T7 RNA polymerase promoter in an expression vector. Then, the growth analysis of E. coli expressing aptamers was observed for 12-hour period. Our analysis indicated that aptamers helped to increase the intracellular concentration of aminoglycosides thereby increasing their efficacy.

  20. The Impact of Efflux Pump Inhibitors on the Activity of Selected Non-Antibiotic Medicinal Products against Gram-Negative Bacteria

    Directory of Open Access Journals (Sweden)

    Agnieszka E. Laudy

    2017-01-01

    Full Text Available The potential role of non-antibiotic medicinal products in the treatment of multidrug-resistant Gram-negative bacteria has recently been investigated. It is highly likely that the presence of efflux pumps may be one of the reasons for the weak activity of non-antibiotics, as in the case of some non-steroidal anti-inflammatory drugs (NSAIDs, against Gram-negative rods. The activity of eight drugs of potential non-antibiotic activity, active substance standards, and relevant medicinal products were analysed with and without of efflux pump inhibitors against 180 strains of five Gram-negative rod species by minimum inhibitory concentration (MIC value determination in the presence of 1 mM MgSO4. Furthermore, the influence of non-antibiotics on the susceptibility of clinical strains to quinolones with or without PAβN (Phe-Arg-β-naphthylamide was investigated. The impacts of PAβN on the susceptibility of bacteria to non-antibiotics suggests that amitriptyline, alendronate, nicergoline, and ticlopidine are substrates of efflux pumps in Gram-negative rods. Amitriptyline/Amitriptylinum showed the highest direct antibacterial activity, with MICs ranging 100–800 mg/L against all studied species. Significant decreases in the MIC values of other active substances (acyclovir, atorvastatin, and famotidine tested with pump inhibitors were not observed. The investigated non-antibiotic medicinal products did not alter the MICs of quinolones in the absence and in the presence of PAβN to the studied clinical strains of five groups of species.

  1. Molecular identification of aminoglycoside-modifying enzymes in clinical isolates of Escherichia coli resistant to amoxicillin/clavulanic acid isolated in Spain.

    Science.gov (United States)

    Fernández-Martínez, Marta; Miró, Elisenda; Ortega, Adriana; Bou, Germán; González-López, Juan José; Oliver, Antonio; Pascual, Alvaro; Cercenado, Emilia; Oteo, Jesús; Martínez-Martínez, Luis; Navarro, Ferran

    2015-08-01

    The activity of eight aminoglycosides (amikacin, apramycin, arbekacin, gentamicin, kanamycin, neomycin, netilmicin and tobramycin) against a collection of 257 amoxicillin/clavulanic acid (AMC)-resistant Escherichia coli isolates was determined by microdilution. Aminoglycoside resistance rates, the prevalence of aminoglycoside-modifying enzyme (AME) genes, the relationship between AME gene detection and resistance phenotype to aminoglycosides, and the association of AME genes with mechanisms of AMC resistance in E. coli isolates in Spain were investigated. Aminoglycoside-resistant isolates were screened for the presence of genes encoding common AMEs [aac(3)-Ia, aac(3)-IIa, aac(3)-IVa, aac(6')-Ib, ant(2″)-Ia, ant(4')-IIa and aph(3')-Ia] or 16S rRNA methylases (armA, rmtB, rmtC and npmA). In total, 105 isolates (40.9%) were resistant to at least one of the aminoglycosides tested. Amikacin, apramycin and arbekacin showed better activity, with MIC90 values of 2mg/L (arbekacin) and 8mg/L (amikacin and apramycin). Kanamycin presented the highest MIC90 (128mg/L). The most common AME gene was aac(6')-Ib (36 strains; 34.3%), followed by aph(3')-Ia (31 strains; 29.5%), ant(2″)-Ia (29 strains; 27.6%) and aac(3)-IIa (23 strains; 21.9%). aac(3)-Ia, aac(3)-IVa, ant(4')-IIa and the four methylases were not detected. The ant(2″)-Ia gene was usually associated with OXA-1 [21/30; 70%], whilst 23/25 (92%) strains producing CTX-M-15 had the aac(6')-Ib gene. The most prevalent AME gene was aac(6')-Ib (18/41; 44%) in nosocomial isolates, whilst ant(2″)-Ia and aph(3')-Ia genes (20/64; 31%) were more frequent in strains of community origin. In 64.6% isolates the phenotypic profile correlated with the presence of commonly encountered AMEs. Copyright © 2015 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  2. Involvement of aph(3‘-IIa in the formation of mosaic aminoglycoside resistance genes in natural environments

    Directory of Open Access Journals (Sweden)

    Markus eWoegerbauer

    2015-05-01

    Full Text Available Intragenic recombination leading to mosaic gene formation is known to alter resistance profiles for particular genes and bacterial species. Few studies have examined to what extent aminoglycoside resistance genes undergo intragenic recombination.We screened the GenBank database for mosaic gene formation in homologs of the aph(3’-IIa (nptII gene. APH(3’-IIa inactivates important aminoglycoside antibiotics. The gene is widely used as a selectable marker in biotechnology and enters the environment via laboratory discharges and the release of transgenic organisms. Such releases may provide opportunities for recombination in competent environmental bacteria.The retrieved GenBank sequences were grouped in 3 datasets comprising river water samples, duck pathogens and full-length variants from various bacterial genomes and plasmids. Analysis for recombination in these datasets was performed with the Recombination Detection Program, RDP4, and the Genetic Algorithm for Recombination Detection, GARD.From a total of 89 homologous sequences, 83% showed 99% - 100% sequence identity with aph(3’-IIa originally described as part of transposon Tn5. Fifty one were unique sequence variants eligible for recombination analysis. Only a single recombination event was identified with high confidence and indicated the involvement of aph(3’-IIa in the formation of a mosaic gene located on a plasmid of environmental origin in the multi-resistant isolate Pseudomonas aeruginosa PA96. The available data suggest that aph(3’-IIa is not an archetypical mosaic gene as the divergence between the described sequence variants and the number of detectable recombination events is low. This is in contrast to the numerous mosaic alleles reported for certain penicillin or tetracycline resistance determinants.

  3. Characterization of paired mucoid/non-mucoid Pseudomonas aeruginosa isolates from Danish cystic fibrosis patients: antibiotic resistance, beta-lactamase activity and RiboPrinting

    DEFF Research Database (Denmark)

    Ciofu, O; Fussing, V; Bagge, N

    2001-01-01

    The purpose of this study was to characterize 42 paired mucoid and non-mucoid Danish cystic fibrosis (CF) Pseudomonas aeruginosa isolates collected in 1997, by RiboPrinting, antibiotic susceptibility and beta-lactamase activity. Eight P. aeruginosa isolates collected before 1991 were included...... for comparison. Eighteen of the 42 paired mucoid and non-mucoid isolates showed the same ribotype; the remaining 24 belonged to different ribogroups. Mucoid isolates showed higher susceptibility to antibiotics and lower beta-lactamase activity compared with non-mucoid isolates. Significant differences (P...... beta-lactamase for the paired isolates...

  4. Prescribing Antibiotics

    DEFF Research Database (Denmark)

    Pedersen, Inge Kryger; Jepsen, Kim Sune

    2018-01-01

    The medical professions will lose an indispensable tool in clinical practice if even simple infections cannot be cured because antibiotics have lost effectiveness. This article presents results from an exploratory enquiry into “good doctoring” in the case of antibiotic prescribing at a time when...

  5. Forgotten antibiotics

    DEFF Research Database (Denmark)

    Pulcini, Céline; Bush, Karen; Craig, William A

    2012-01-01

    In view of the alarming spread of antimicrobial resistance in the absence of new antibiotics, this study aimed at assessing the availability of potentially useful older antibiotics. A survey was performed in 38 countries among experts including hospital pharmacists, microbiologists, and infectious...

  6. Chemical Composition, Antibacterial Activity, and Synergistic Effects with Conventional Antibiotics and Nitric Oxide Production Inhibitory Activity of Essential Oil from Geophila repens (L. I.M. Johnst

    Directory of Open Access Journals (Sweden)

    Huijuanzi Rao

    2017-09-01

    Full Text Available Geophila repens (L. I.M. Johnst, a perennial herb, belongs to the Rubiaceae family. In this study, we identified the chemical composition of the Geophila repens essential oil (GR-EO for the first time. Totally, seventy-seven compounds were identified according to GC and GC-MS, which represent 98.0% of the oil. And the major components of GR-EO were β-caryophyllene (23.3%, β-elemene (8.0%, farnesyl butanoate (7.4%, myrcene (3.5%, and trans-nerolidol (3.3%. Then we evaluated the antibacterial activities of GR-EO and the synergistic effects of GR-EO in combination with commercial antibiotics using the microdilution and Checkerboard method. The results demonstrated that GR-EO possessed an excellent broad spectrum antibacterial activity, especially against Pseudomonas aeruginosa and Bacillus subtilis. It also showed that the combined application of GR-EO with antibiotics led to synergistic effects in most cases. And the most prominent synergistic effect was noticed when GR-EO was in combination with Streptomycin and tested against Escherichia coli (fractional inhibitory concentration indices (FICI of 0.13. Additionally, the results of a Griess assay revealed that GR-EO exhibited a potent inhibitory effect on NO production in lipopolysaccharide (LPS-activated RAW 264.7 (murine macrophage cells. In conclusion, the combination of GR-EO and the commercial antibiotics has significant potential for the development of new antimicrobial treatment and reduction of drug resistance.

  7. Efficacy of needle irrigation, EndoActivator, and photon-initiated photoacoustic streaming technique on removal of double and triple antibiotic pastes.

    Science.gov (United States)

    Arslan, Hakan; Akcay, Merve; Capar, Ismail Davut; Ertas, Hüseyin; Ok, Evren; Uysal, Banu

    2014-09-01

    Photon-induced photoacoustic streaming (PIPS) is a novel technique used for the removal of material on root canal walls, such as bacteria and the smear layer. This study evaluated the efficacy of needle irrigation, the EndoActivator System (Dentsply Tulsa Dental Specialties, Tulsa, OK), and PIPS on the removal of antibiotic pastes from an artificial groove created in a root canal. Root canal preparation was performed up to size #40 on 84 extracted single-rooted teeth using ProTaper rotary instruments (Dentsply Maillefer, Ballaigues, Switzerland). The specimens were then split longitudinally, and 2 standardized grooves were prepared in the coronal and apical part of each segment. Double (DAP) and triple antibiotic pastes (TAP) were placed in the grooves for 4 weeks, and the root halves were reassembled. Needle irrigation, the EndoActivator System, and PIPS were used for the removal of DAP and TAP. The root segments were disassembled, and the amount of remaining antibiotic pastes was evaluated under a stereomicroscope at 20× magnification using a 4-grade scoring system. The data were evaluated statistically using Mann-Whitney U tests with a 95% confidence level (P = .05). PIPS removed significantly more antibiotic pastes than the EndoActivator and needle irrigation (P irrigation in removing antibiotic pastes (P .05). PIPS was more effective in removing both DAP and TAP from artificial grooves in root canals than the EndoActivator System and needle irrigation. The EndoActivator was also more effective than needle irrigation. It is difficult to completely remove antibiotic pastes from root canals. Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  8. Antibiotic Resistance

    DEFF Research Database (Denmark)

    Hansen, Malene Plejdrup; Hoffmann, Tammy C; McCullough, Amanda R

    2015-01-01

    Numerous opportunities are available in primary care for alleviating the crisis of increasing antibiotic resistance. Preventing patients from developing an acute respiratory infection (ARI) will obviate any need for antibiotic use downstream. Hygiene measures such as physical barriers and hand...... will greatly improve the use of antibiotics for ARIs. However, used in concert, combinations are likely to enable clinicians and health care systems to implement the strategies that will reduce antimicrobial resistance in the future....... antibiotic prescribing are a major factor in the prescribing for ARIs. Professional interventions with educational components are effective, although they have modest effects, and are expensive. GPs' perceptions - that mistakenly assume as a default that patients want antibiotics for their ARIs - are often...

  9. Comparative study of antibacterial activity of wood-decay fungi and antibiotics

    Directory of Open Access Journals (Sweden)

    A. F. Md. Hassan Iftekhar

    2011-03-01

    Full Text Available The antibacterial effects of three mushrooms extract Ganoderma lucidum, Auricularia auricula, Pleurotus florida were studied against Staphylococcus aureus and Escherichia coli. A. auricula showed significant antibacterial activity against S. aureus. P. florida showed some antibacterial activity while G. lucidum showed no antibacterial activity. None of the extracts showed any activity against E. coli.

  10. A conformational switch in the active site of BT_2972, a methyltransferase from an antibiotic resistant pathogen B. thetaiotaomicron.

    Directory of Open Access Journals (Sweden)

    Veerendra Kumar

    Full Text Available Methylation is one of the most common biochemical reactions involved in cellular and metabolic functions and is catalysed by the action of methyltransferases. Bacteroides thetaiotaomicron is an antibiotic-resistant bacterium that confers resistance through methylation, and as yet, there is no report on the structure of methyltransferases from this bacterium. Here, we report the crystal structure of an AdoMet-dependent methyltransferase, BT_2972 and its complex with AdoMet and AdoHcy for B. thetaiotaomicron VPI-5482 strain along with isothermal titration calorimetric assessment of the binding affinities. Comparison of the apo and complexed BT_2972 structures reveals a significant conformational change between open and closed forms of the active site that presumably regulates the association with cofactors and may aid interaction with substrate. Together, our analysis suggests that BT_2972 is a small molecule methyltransferase and might catalyze two O-methylation reaction steps involved in the ubiquinone biosynthesis pathway.

  11. The effect of systemic antibiotics administered during the active phase of non-surgical periodontal therapy or after the healing phase: a systematic review

    Directory of Open Access Journals (Sweden)

    Aretuza FRITOLI

    2015-06-01

    Full Text Available Objective The aim of this systematic review was to compare the clinical effectiveness of systemic antibiotics administered in the active stage of periodontal treatment or after the healing phase. Material and Methods An electronic search was performed in the databases EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA statement. A manual search of the reference list of selected studies and of review articles was also performed up to November 2013. Randomized Clinical Trials (RCT that evaluated the systemic administration of antibiotics as adjuvants to scaling and root planning (SRP at different phases of periodontal treatment were included. Systematic reviews and studies that evaluated subjects with systemic diseases and those that used subantimicrobial doses of antibiotics were excluded. Results The initial search identified 1,039 articles, of which seven were selected, and only one met the inclusion criteria. This study showed that subjects taking metronidazole and amoxicillin at the initial phase of treatment exhibited statistically significantly greater reduction in pocket depth and gain in clinical attachment level in initially deep sites (PD≥7 mm than subjects taking antibiotics after healing (p<0.05. This comparison was conducted 2 months after antibiotic intake, at the healing phase. Conclusion To date, only one short-term RCT has directly compared different moments of systemic antibiotics administration, as adjuncts to SRP, in the treatment of periodontitis. Although the results of this study suggested some benefits for antibiotics intake during the active phase of therapy, these findings need to be confirmed by larger placebo-controlled randomized clinical trials with longer follow-up periods.

  12. Conjugative DNA transfer induces the bacterial SOS response and promotes antibiotic resistance development through integron activation.

    Directory of Open Access Journals (Sweden)

    Zeynep Baharoglu

    2010-10-01

    Full Text Available Conjugation is one mechanism for intra- and inter-species horizontal gene transfer among bacteria. Conjugative elements have been instrumental in many bacterial species to face the threat of antibiotics, by allowing them to evolve and adapt to these hostile conditions. Conjugative plasmids are transferred to plasmidless recipient cells as single-stranded DNA. We used lacZ and gfp fusions to address whether conjugation induces the SOS response and the integron integrase. The SOS response controls a series of genes responsible for DNA damage repair, which can lead to recombination and mutagenesis. In this manuscript, we show that conjugative transfer of ssDNA induces the bacterial SOS stress response, unless an anti-SOS factor is present to alleviate this response. We also show that integron integrases are up-regulated during this process, resulting in increased cassette rearrangements. Moreover, the data we obtained using broad and narrow host range plasmids strongly suggests that plasmid transfer, even abortive, can trigger chromosomal gene rearrangements and transcriptional switches in the recipient cell. Our results highlight the importance of environments concentrating disparate bacterial communities as reactors for extensive genetic adaptation of bacteria.

  13. Montmorillonite enhanced ciprofloxacin transport in saturated porous media with sorbed ciprofloxacin showing antibiotic activity

    Science.gov (United States)

    Chen, Hao; Gao, Bin; Yang, Liu-Yan; Ma, Lena Q.

    2015-02-01

    Antibiotic ciprofloxacin (CIP) is immobile in the subsurface but it has been frequently detected in the aquatic system. Therefore it is important to investigate the factors impacting CIP's mobilization in aquifer. Laboratory columns packed with sand were used to test colloid-facilitated CIP transport by 1) using kaolinite or montmorillonite to mobilize presorbed-CIP in a column or 2) co-transporting with CIP by pre-mixing them before transport. The Langmuir model showed that CIP sorption by montmorillonite (23 g kg- 1) was 100 times more effective than sand or kaolinite. Even with strong CIP complexation ability to Fe/Al coating on sand surface, montmorillonite promoted CIP transport, but not kaolinite. All presorbed-CIP by sand was mobilized by montmorillonite after 3 pore volumes through co-transporting of CIP with montmorillonite. The majority of CIP was fixed onto the montmorillonite interlayer but still showed inhibition of bacteria growth. Our results suggested that montmorillonite with high CIP sorption ability can act as a carrier to enhance CIP's mobility in aquifer.

  14. Pattern of Infection and Antibiotic Activity among Streptococcus agalactiae Isolates from Adults in Mashhad, Iran

    Directory of Open Access Journals (Sweden)

    Masoumeh Malek-Jafarian

    2015-05-01

    Full Text Available Background: One of the main causes of sexually transmitted diseases is group B β- hemolytic streptococci (GBS multiplying in the genital tracts. Penicillin is the most common drug for the treatment of infections caused by these bacteria, but in patients suffering from Penicillin allergy, Erythromycin and Clindamycin are used as alternative therapeutic drugs against GBS. Recently, resistance to these drugs has been reported more often. In this study, efforts have been made to determine the prevalence and antibiotic resistance of GBS. Methods: Modified Christie Atkins Munch-Petersen (CAMP test was conducted on over 2400 samples of urine and discharge taken from vagina, urethra and prostate. The drug sensitivity was performed by double disk sensitivity tests to Bacitracin, Trimethoprim, and Sulfamethoxazole and then the resistant samples were investigated by E-test to determine the minimal inhibitory concentrations (MICs value. Results: Twenty-three vaginal and 10 urethral discharge, 27urine and 6 prostatic secretion samples were GBS positive. The most symbiotic microorganisms with GBS were strains of Enterococci (90%, Staphylococcus saprophyticus (25% and Candida albicans (6%. The disk diffusion method showed 18 cases with Penicillin resistance (MIC: 1.5 mg/ml. Conclusion: Taken together, GBS carriers’ rate in this study was found 20.65% (8.24% men and 12.4% women. Furthermore, findings showed high-level resistance to Erythromycin and Clindamycin.

  15. Enhanced removal of sulfonamide antibiotics by KOH-activated anthracite coal: Batch and fixed-bed studies

    International Nuclear Information System (INIS)

    Zuo, Linzi; Ai, Jing; Fu, Heyun; Chen, Wei; Zheng, Shourong; Xu, Zhaoyi; Zhu, Dongqiang

    2016-01-01

    The presence of sulfonamide antibiotics in aquatic environments poses potential risks to human health and ecosystems. In the present study, a highly porous activated carbon was prepared by KOH activation of an anthracite coal (Anth-KOH), and its adsorption properties toward two sulfonamides (sulfamethoxazole and sulfapyridine) and three smaller-sized monoaromatics (phenol, 4-nitrophenol and 1,3-dinitrobenzene) were examined in both batch and fixed-bed adsorption experiments to probe the interplay between adsorbate molecular size and adsorbent pore structure. A commercial powder microporous activated carbon (PAC) and a commercial mesoporous carbon (CMK-3) possessing distinct pore properties were included as comparative adsorbents. Among the three adsorbents Anth-KOH exhibited the largest adsorption capacities for all test adsorbates (especially the two sulfonamides) in both batch mode and fixed-bed mode. After being normalized by the adsorbent surface area, the batch adsorption isotherms of sulfonamides on PAC and Anth-KOH were displaced upward relative to the isotherms on CMK-3, likely due to the micropore-filling effect facilitated by the microporosity of adsorbents. In the fixed-bed mode, the surface area-normalized adsorption capacities of Anth-KOH for sulfonamides were close to that of CMK-3, and higher than that of PAC. The irregular, closed micropores of PAC might impede the diffusion of the relatively large-sized sulfonamide molecules and in turn led to lowered fixed-bed adsorption capacities. The overall superior adsorption of sulfonamides on Anth-KOH can be attributed to its large specific surface area (2514 m 2 /g), high pore volume (1.23 cm 3 /g) and large micropore sizes (centered at 2.0 nm). These findings imply that KOH-activated anthracite coal is a promising adsorbent for the removal of sulfonamide antibiotics from aqueous solution. - Highlights: • A high efficiency adsorbent for sulfonamide removal is prepared from anthracite. • Effects of

  16. Associations between active trachoma and community intervention with Antibiotics, Facial cleanliness, and Environmental improvement (A,F,E.

    Directory of Open Access Journals (Sweden)

    Jeremiah Ngondi

    2008-04-01

    Full Text Available Surgery, Antibiotics, Facial cleanliness and Environmental improvement (SAFE are advocated by the World Health Organization (WHO for trachoma control. However, few studies have evaluated the complete SAFE strategy, and of these, none have investigated the associations of Antibiotics, Facial cleanliness, and Environmental improvement (A,F,E interventions and active trachoma. We aimed to investigate associations between active trachoma and A,F,E interventions in communities in Southern Sudan.Surveys were undertaken in four districts after 3 years of implementation of the SAFE strategy. Children aged 1-9 years were examined for trachoma and uptake of SAFE assessed through interviews and observations. Using ordinal logistic regression, associations between signs of active trachoma and A,F,E interventions were explored. Trachomatous inflammation-intense (TI was considered more severe than trachomatous inflammation-follicular (TF. A total of 1,712 children from 25 clusters (villages were included in the analysis. Overall uptake of A,F,E interventions was: 53.0% of the eligible children had received at least one treatment with azithromycin; 62.4% children had a clean face on examination; 72.5% households reported washing faces of children two or more times a day; 73.1% households had received health education; 44.4% of households had water accessible within 30 minutes; and 6.3% households had pit latrines. Adjusting for age, sex, and district baseline prevalence of active trachoma, factors independently associated with reduced odds of a more severe active trachoma sign were: receiving three treatments with azithromycin (odds ratio [OR] = 0.1; 95% confidence interval [CI] 0.0-0.4; clean face (OR = 0.3; 95% CI 0.2-0.4; washing faces of children three or more times daily (OR = 0.4; 95% CI 0.3-0.7; and presence and use of a pit latrine in the household (OR = 0.4; 95% CI 0.2-0.9.Analysis of associations between the A,F,E components of the SAFE strategy and

  17. Investigation on Antibacterial and Antioxidant Activities, Phenolic and Flavonoid Contents of Some Thai Edible Plants as an Alternative for Antibiotics

    Directory of Open Access Journals (Sweden)

    J. H. Lee

    2014-10-01

    Full Text Available This study was aimed to examine the antibacterial and antioxidative properties of seven edible plants from Thailand to develop alternative antibiotics as feed additives. The plants include Citrus aurantifolia Swingle (Lime fruits and its leaves, Sesbania grandiflora L. (Agati sesbania leaves, Piper sarmentosum Roxb (Wild betal leaves, Curcuma domestica Valeton (Turmeric roots, Morinda citrifolia L. (Beach mulberry leaves, Cassia siamea britt (Siamea cassia leaves, and Cocos nucifera L. (Coconut peels. The plants were extracted by methanol, n-hexane, chloroform, ethyl acetate, butanol and water. Antibacterial activities with minimum inhibitory concentration (MIC were determined by agar diffusion assay against Escherichia coli, Burkholderia sp., Haemopilus somnus, Haemopilus parasuis, and Clostridium perfringens that were considered pathogenic strains in livestock infection. Methanol extracts of C. aurantifolia Swingle fruits and leaves showed the broadest spectrum of antibacterial activities except for C. perfringens. Butanol extract of S. grandiflora L. leaves showed the strongest activity against Burkholderia sp. with MIC, 135 μg/mL. P. sarmentosum Roxb leaves showed antibacterial activities against E. coli, Burkholderia sp. and H. parasuis. Ethyl acetate and water extracts from C. domesitca Valeton roots showed MIC of 306 μg/mL and 183 μg/mL, respectively against only C. perfringens. Antioxidative activity was determined by 2-diphenyl-2-picryl hydrazyl photometric assay. The methanol extracts of C. aurantifolia Swingle fruits and P. sarmentosum Roxb leaves showed the highest antioxidant activity among all the extracts with 3.46 mg/mL and 2.70 mg/mL effective concentration 50% (EC50 values, respectively. Total contents of phenolics and flavonoids were measured from the plant extracts. Methanol extracts of S. grandiflora L. and chloroform extracts of C. domestica Valeton were found to have the highest amount of total phenolics, 41.7 and 47

  18. Investigation on antibacterial and antioxidant activities, phenolic and flavonoid contents of some thai edible plants as an alternative for antibiotics.

    Science.gov (United States)

    Lee, J H; Cho, S; Paik, H D; Choi, C W; Nam, K T; Hwang, S G; Kim, S K

    2014-10-01

    This study was aimed to examine the antibacterial and antioxidative properties of seven edible plants from Thailand to develop alternative antibiotics as feed additives. The plants include Citrus aurantifolia Swingle (Lime) fruits and its leaves, Sesbania grandiflora L. (Agati sesbania) leaves, Piper sarmentosum Roxb (Wild betal) leaves, Curcuma domestica Valeton (Turmeric) roots, Morinda citrifolia L. (Beach mulberry) leaves, Cassia siamea britt (Siamea cassia) leaves, and Cocos nucifera L. (Coconut) peels. The plants were extracted by methanol, n-hexane, chloroform, ethyl acetate, butanol and water. Antibacterial activities with minimum inhibitory concentration (MIC) were determined by agar diffusion assay against Escherichia coli, Burkholderia sp., Haemopilus somnus, Haemopilus parasuis, and Clostridium perfringens that were considered pathogenic strains in livestock infection. Methanol extracts of C. aurantifolia Swingle fruits and leaves showed the broadest spectrum of antibacterial activities except for C. perfringens. Butanol extract of S. grandiflora L. leaves showed the strongest activity against Burkholderia sp. with MIC, 135 μg/mL. P. sarmentosum Roxb leaves showed antibacterial activities against E. coli, Burkholderia sp. and H. parasuis. Ethyl acetate and water extracts from C. domesitca Valeton roots showed MIC of 306 μg/mL and 183 μg/mL, respectively against only C. perfringens. Antioxidative activity was determined by 2-diphenyl-2-picryl hydrazyl photometric assay. The methanol extracts of C. aurantifolia Swingle fruits and P. sarmentosum Roxb leaves showed the highest antioxidant activity among all the extracts with 3.46 mg/mL and 2.70 mg/mL effective concentration 50% (EC50) values, respectively. Total contents of phenolics and flavonoids were measured from the plant extracts. Methanol extracts of S. grandiflora L. and chloroform extracts of C. domestica Valeton were found to have the highest amount of total phenolics, 41.7 and 47.8

  19. The Comparison Among Antibacterial Activity of Mespilus germanica Extracts and Number of Common Therapeutic Antibiotics “In Vitro”

    Directory of Open Access Journals (Sweden)

    Farideh Tabatabaei-Yazdi

    2015-12-01

    Full Text Available Background: Antibiotic resistance is a serious and growing phenomenon in contemporary medicine and has emerged as one of the pre-eminent public health concerns of the 21st century. Objectives: In this study, antibacterial activity of Mespilus germanica extract against some pathogenic bacterial strains (Streptococcus pyogene, Listeria innocua, Enterobacter aerogenes and Klebsiella pneumoniae was evaluated. Materials and Methods: In this experimental study, maceration extraction method was used for M. germanica extract. Disk diffusion method was used to evaluate the antimicrobial effect and broth microdilution method was used to determine the minimum inhibitory concentration and minimum bactericidal concentration. Then, the data were entered into the SPSS-18 statistical software and analyzed using one-way ANOVA and Tukey test. Results: Antimicrobial activity was assessed by inhibition diameters which were found to range from 8 to 21.5 mm for the two extracts against all the bacterial strains tested. The minimum inhibitory concentrations (MIC for the extracts were later determined by three fold serial dilutions method and they ranged 2 - 64 mg/mL against all the strains and minimum bactericidal concentrations (MBC for the extracts were later determined by three fold serial dilutions method and they ranged 4 - 128 mg/mL against all the strains. Conclusions: The M. germanica extract showed the more effective impact on the growth S. pyogene and L. innocua than E. aerogenes and K. pneumoniae (P < 0.05. M. germanica in comparison with common therapeutic antibiotics had more inhibitory effect on some of the studied strains in vitro.

  20. Assessment of virulence factors, antibiotic resistance and amino-decarboxylase activity in Enterococcus faecium MXVK29 isolated from Mexican chorizo.

    Science.gov (United States)

    Alvarez-Cisneros, Y M; Fernández, F J; Sainz-Espuñez, T; Ponce-Alquicira, E

    2017-02-01

    Enterococcus faecium MXVK29 has the ability to produce an antimicrobial compound that belongs to Class IIa of the Klaenhammer classification, and could be used as part of a biopreservation technology through direct inoculation of the strain as a starter or protective culture. However, Enterococcus is considered as an opportunistic pathogen, hence, the purpose of this work was to study the food safety determinants of E. faecium MXVK29. The strain was sensitive to all of the antibiotics tested (penicillin, tetracycline, vancomycin, erythromycin, chloramphenicol, gentamicin, neomycin, kanamycin and netilmicin) and did not demonstrate histamine, cadaverine or putrescine formation. Furthermore, tyrosine-decarboxylase activity was detected by qualitative assays and PCR. Among the virulence factors analysed for the strain, only the genes encoding the sexual pheromone cCF10 precursor lipoprotein (ccf) and cell-wall adhesion (efaA fm ) were amplified. The presence of these genes has low impact on pathogenesis, as there are no other genes encoding for virulence factors, such as aggregation proteins. Therefore, Enterococcus faecium could be employed as part of a bioconservation method, because it does not produce risk factors for consumer's health; in addition, it could be used as part of the hurdle technology in foods. The use of molecular techniques has allowed, in recent years, to detect pathogenicity genes present in the genome of starter cultures used in food processing and preservation. The presence of these genes is undesirable, because horizontal transfer may occur with the natural biota of consumers. For this reason, it is important to analyse the presence of pathogenicity genes in such cultures. In this work, virulence factors and antibiotic resistance of Enterococcus faecium strain MXVK29, producing an antimicrobial compound with high antilisterial activity, were analysed. The results indicate that the strain is safe to be used in food processing as starter

  1. Constitutive presence of antibiotic resistance genes within the bacterial community of a large subalpine lake.

    Science.gov (United States)

    Di Cesare, Andrea; Eckert, Ester M; Teruggi, Alessia; Fontaneto, Diego; Bertoni, Roberto; Callieri, Cristiana; Corno, Gianluca

    2015-08-01

    The fate of antibiotic resistance genes (ARGs) in environmental microbial communities is of primary concern as prodromal of a potential transfer to pathogenic bacteria. Although of diverse origin, the persistence of ARGs in aquatic environments is highly influenced by anthropic activities, allowing potential control actions in well-studied environments. However, knowledge of abundance and space-time distribution of ARGs in ecosystems is still scarce. Using quantitative real-time PCR, we investigated the presence and the abundance of twelve ARGs (against tetracyclines, β-lactams, aminoglycosides, quinolones and sulphonamides) at different sampling sites, depths and seasons, in Lake Maggiore, a large subalpine lake, and in the area of its watershed. We then evaluated the correlation between each ARG and a number of ecological parameters in the water column in the deepest part of the lake. Our results suggest the constitutive presence of at least four ARGs within the bacterial community with a high proportion of bacteria potentially resistant to tetracyclines and sulphonamides. The presence of these ARGs was independent of the total bacterial density and temperature. The dynamics of tet(A) and sulII genes were, however, positively correlated with dissolved oxygen and negatively to chlorophyll a, suggesting that the resistant microbes inhabit specific niches. These observations indicate that the lake is a reservoir of antibiotic resistances, highlighting the need of a deeper understanding of the sources of ARGs and the factors allowing their persistence in waters. © 2015 John Wiley & Sons Ltd.

  2. Assessment of antibiotic resistance in Klebsiella pneumoniae exposed to sequential in vitro antibiotic treatments

    OpenAIRE

    Kim, Jeongjin; Jo, Ara; Chukeatirote, Ekachai; Ahn, Juhee

    2016-01-01

    Background Bacteria treated with different classes of antibiotics exhibit changes in susceptibility to successive antibiotic treatments. This study was designed to evaluate the influence of sequential antibiotic treatments on the development of antibiotic resistance in Klebsiella pneumoniae associated with ?-lactamase and efflux pump activities. Methods The antibiotic susceptibility, ?-lactamase activity, and efflux activity were determined in K. pneumoniae grown at 37??C by adding initial (0...

  3. The major aminoglycoside-modifying enzyme AAC(3)-II found in Escherichia coli determines a significant disparity in its resistance to gentamicin and amikacin in China.

    Science.gov (United States)

    Xiao, Yonghong; Hu, Yunjian

    2012-02-01

    The aim of this study was to investigate the prevalence of aminoglycoside-modifying enzymes in Escherichia coli in different areas of China and to explore the relationship between pandemic enzyme type and bacterial resistance to antimicrobial agents in China. Gentamicin- or etimicin-resistant clinical isolates of E. coli were collected from different areas of China, and the in vitro antibacterial activity of 11 aminoglycoside agents was determined using standard (Clinical and Laboratory Standards Institute) agar dilution methods. Twelve aminoglycoside-modifying enzyme genes were detected by PCR and confirmed by DNA sequencing. A total of 205 E. coli strains were collected from nine hospitals in seven cities. All strains were highly resistant to gentamicin or etimicin, whereas resistance to tobramycin, netilmicin, and kanamycin was slightly lower. However, less than 15% of isolates were resistant to amikacin and isepamicin. Of the gentamicin-resistant strains, 88.2% and 86.7% were sensitive to isepamicin and amikacin, respectively. Five aminoglycoside-modifying enzyme genes were detected in 191 strains, whereas the remaining 14 strains were negative. The most common gene type was aac(3)-II (162 strains), followed by aac(6')-I (50 strains), ant(3″)-I (28 strains), aph(3')-II (20 strains), and ant(2″)-I (20 strains). Ninety-five strains yielded aac(3)-II only, whereas the others contained two or three genes. The three main gene combinations were aac(6')-I/aac(3)-II (28 strains), aac(3)-II/ant(3″)-I (11 strains), and aac(3)-II/aac(6')-I (10 strains). Regional bacterial resistance and enzyme distribution were roughly similar, although minor differences were found in Guangzhou, Jinan, and Dalian, which were the sources of most of the amikacin- or isepamicin-resistant strains. Chinese clinical isolates of E. coli remain highly resistant to gentamicin and etimicin, but are susceptible to amikacin and isepamicin. The dominant type of aminoglycoside-modifying enzyme

  4. Aged garlic extract, garlic powder extract, S-allylcysteine, diallyl sulfide and diallyl disulfide do not interfere with the antibiotic activity of gentamicin.

    Science.gov (United States)

    Maldonado, Perla D; Chánez-Cárdenas, María Elena; Pedraza-Chaverrí, José

    2005-03-01

    It was shown that aged garlic extract (AGE), garlic powder and the following garlic-derived compounds: S-allylcysteine (SAC), diallyl sulfide (DAS) and diallyl disulfide (DADS), ameliorate gentamicin (GM)-induced nephrotoxicity in rats. However, it was not established if the above mentioned extracts and compounds of garlic could interfere with the antibiotic action of GM. To address this point, AGE, garlic powder extract (GPE), SAC, DAS and DADS were assessed for their ability to interfere with the in vitro antibiotic activity of GM in Escherichia coli cultures. It was found that the above mentioned extracts and compounds of garlic were unable to decrease the antibiotic capacity of GM and even SAC, DAS and DADS alone inhibited the growth of Escherichia coli and enhanced the antibiotic effect of GM. Our data show that SAC, DAS and DADS are antibacterial compounds against E. coli and suggest that AGE, GPE, SAC, DAS and[sol ]or DADS may be administered along with GM-treatment to ameliorate GM-induced nephrotoxicity without interfering with its antibiotic activity. Copyright 2005 John Wiley & Sons, Ltd.

  5. Enzymatic method for inactivation of aminoglycosides during measurement of postantibiotic effect

    NARCIS (Netherlands)

    J.G. den Hollander (Jan); J.W. Mouton (Johan); I.A.J.M. Bakker-Woudenberg (Irma); F.P. Vleggaar (Frank); M.P.J. van Goor (Marie-Louise); H.A. Verbrugh (Henri)

    1996-01-01

    textabstractTo determine the postantibiotic effect of aminoglycosides, two methods are currently being used to remove the test drug: repeated washing and dilution. An enzymatic inactivation method of removing gentamicin and tobramycin was developed and compared with the dilution

  6. novel 6'-n-aminoglycoside acetyltransferase AAC(6')-Iaj from a clinical isolate of Pseudomonas aeruginosa.

    Science.gov (United States)

    Tada, Tatsuya; Miyoshi-Akiyama, Tohru; Shimada, Kayo; Shimojima, Masahiro; Kirikae, Teruo

    2013-01-01

    Pseudomonas aeruginosa NCGM1588 has a novel chromosomal class 1 integron, In151, which includes the aac(6')-Iaj gene. The encoded protein, AAC(6')-Iaj, was found to consist of 184 amino acids, with 70% identity to AAC(6')-Ia. Escherichia coli transformed with a plasmid containing the aac(6')-Iaj gene acquired resistance to all aminoglycosides tested except gentamicin. Of note, aac(6')-Iaj contributed to the resistance to arbekacin. Thin-layer chromatography revealed that AAC(6')-Iaj acetylated all aminoglycosides tested except gentamicin. These findings indicated that AAC(6')-Iaj is a functional acetyltransferase that modifies the amino groups at the 6' positions of aminoglycosides and contributes to aminoglycoside resistance of P. aeruginosa NCGM1588, including arbekacin.

  7. OCCURRENCE OF HIGH-LEVEL AMINOGLYCOSIDE RESISTANCE IN ENVIRONMENTAL ISOLATES OF ENTEROCOCCI

    Science.gov (United States)

    High-level resistance fo aminoglycosides was observed in environmental isolates of enterococci. Various aquatic habitats, including agricultural runoff, creeks, rivers, wastewater, and wells, were analyzed. Strains of Enterococcus faecalis, e.faecium, E. gallinarum, and other Ent...

  8. Antibacterial activity of exogenous glutathione and its synergism on antibiotics sensitize carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

    Science.gov (United States)

    Alharbe, Roaa; Almansour, Ayidh; Kwon, Dong H

    2017-10-01

    A major clinical impact of A. baumannii is hospital-acquired infections including ventilator-associated pneumonia. The treatment of this pathogen is often difficult due to its innate and acquired resistance to almost all commercially available antibiotics. Infections with carbapenem-associated multidrug resistant A. baumannii is the most problematic. Glutathione is a tripeptide thiol-antioxidant and antibacterial activity of exogenous glutathione was reported in some bacteria. However, clinical relevance and molecular details of the antibacterial activity of glutathione are currently unclear. Seventy clinical isolates of A. baumannii including 63 carbapenem-associated multidrug resistant isolates and a type strain A. baumannii ATCC 19606 were used to determine minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Fractional inhibitory concentration (FIC) and time-killing activity with meropenem and/or glutathione were also determined in the carbapenem-associated multidrug resistant isolates. In addition, the roles of exogenous glutathione in multidrug efflux pumps and β-lactamase production were examined. Levels of MIC and MBC were ranged from 10 to 15mM of exogenous glutathione. All tested carbapenem-associated multidrug resistant isolates were sensitized by all tested antibiotics in combination with subinhibitory concentrations of glutathione. FIC levels of glutathione with carbapenem (meropenem) were allcarbapenem-associated multidrug resistant isolates were killed by subinhibitory concentrations of both glutathione and meropenem at>2log10 within 12h, suggesting glutathione synergistically interacts with meropenem. The roles of multidrug efflux pumps and β-lactamase production were excluded for the glutathione-mediated antibiotic susceptibility. Overall results demonstrate that the antibacterial activity of glutathione is clinically relevant and its synergism on antibiotics sensitizes clinical isolates of A. baumannii regardless

  9. Selection of antibiotic resistance at very low antibiotic concentrations.

    Science.gov (United States)

    Sandegren, Linus

    2014-05-01

    Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed.

  10. Environmental pollution by antibiotics and by antibiotic resistance determinants

    International Nuclear Information System (INIS)

    Martinez, Jose Luis

    2009-01-01

    Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations. - The article reviews the current knowledge on the effects that pollution by antibiotics and antibiotic resistance genes may have for the microbiosphere.

  11. Environmental pollution by antibiotics and by antibiotic resistance determinants

    Energy Technology Data Exchange (ETDEWEB)

    Martinez, Jose Luis, E-mail: jlmtnez@cnb.csic.e [Departamento de Biotecnologia Microbiana, Centro Nacional de Biotecnologia, Consejo Superior de Investigaciones Cientificas, Darwin 3, Cantoblanco, 28049 Madrid, and CIBERESP (Spain)

    2009-11-15

    Antibiotics are among the most successful drugs used for human therapy. However, since they can challenge microbial populations, they must be considered as important pollutants as well. Besides being used for human therapy, antibiotics are extensively used for animal farming and for agricultural purposes. Residues from human environments and from farms may contain antibiotics and antibiotic resistance genes that can contaminate natural environments. The clearest consequence of antibiotic release in natural environments is the selection of resistant bacteria. The same resistance genes found at clinical settings are currently disseminated among pristine ecosystems without any record of antibiotic contamination. Nevertheless, the effect of antibiotics on the biosphere is wider than this and can impact the structure and activity of environmental microbiota. Along the article, we review the impact that pollution by antibiotics or by antibiotic resistance genes may have for both human health and for the evolution of environmental microbial populations. - The article reviews the current knowledge on the effects that pollution by antibiotics and antibiotic resistance genes may have for the microbiosphere.

  12. Aminoglycosides in septic shock: an overview, with specific consideration given to their nephrotoxic risk.

    Science.gov (United States)

    Boyer, Alexandre; Gruson, Didier; Bouchet, Stéphane; Clouzeau, Benjamin; Hoang-Nam, Bui; Vargas, Frédéric; Gilles, Hilbert; Molimard, Mathieu; Rogues, Anne-Marie; Moore, Nicholas

    2013-04-01

    Aminoglycoside nephrotoxicity has been reported in patients with sepsis, and several risk factors have been described. Once-daily dosing and shorter treatment have reduced nephrotoxicity risk, and simplified aminoglycoside monitoring. This review focuses on nephrotoxicity associated with aminoglycosides in the subset of patients with septic shock or severe sepsis. These patients are radically different from those with less severe sepsis. They may have, for instance, renal impairment due to the shock per se, sepsis-related acute kidney injury, frequent association with pre-existing risk factors for renal failure such as diabetes, dehydration and other nephrotoxic treatments. In this category of patients, these risk factors might modify substantially the benefit-risk ratio of aminoglycosides. In addition, aminoglycoside administration in critically ill patients with sepsis is complicated by an extreme inter- and intra-individual variability in drug pharmacokinetic/pharmacodynamic characteristics: the volume of distribution (Vd) is frequently increased while the elimination constant can be either increased or decreased. Consequently, and although its effect on nephrotoxicity has not been explored, a different administration schedule, i.e. a high-dose once daily (HDOD), and several therapeutic drug monitoring (TDM) options have been proposed in these patients. This review describes the historical perspective of these different options, including those applying to subsets of patients in which aminoglycoside administration is even more complex (obese intensive care unit [ICU] patients, patients needing continuous or discontinuous renal replacement therapy [CRRT/DRRT]). A simple linear dose adjustment according to aminoglycoside serum concentration can be classified as low-intensity TDM. Nomograms have also been proposed, based on the maximum (peak) plasma concentration (Cmax) objectives, weight and creatinine clearance. The Sawchuk and Zaske method (based on the

  13. In vitro determination of the antibiotic susceptibility of biofilm-forming Pseudomonas aeruginosa and Staphylococcus aureus: possible role of proteolytic activity and membrane lipopolysaccharide

    Directory of Open Access Journals (Sweden)

    Masadeh MM

    2013-03-01

    Full Text Available Majed M Masadeh,1 Nizar M Mhaidat,2 Karem H Alzoubi,2 Emad I Hussein,3 Esra’a I Al-Trad41Department of Pharmaceutical Technology, 2Department of Clinical Pharmacy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Biological Sciences, Yarmouk University, Irbid, Jordan; 4Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, Jordan University of Science and Technology, Irbid, JordanAbstract: We carried out a comprehensive overview of inhibitory effects of selected antibiotics on planktonic and biofilm cells of Staphylococcus aureus (ATCC 29213 and Pseudomonas aeruginosa (ATCC 27853 strains. The possible involvement of protease activity and the lipopolysaccharide (LPS profile of P. aeruginosa were also analyzed. Biofilm cells of both strains were more resistant to antibiotics than their planktonic counterparts. Protease activity was increased in both strains in the biofilm forms. Challenge with sublethal doses of antibiotics also increased proteolytic activity of biofilm cells. Additionally, the LPS profile of P. aeruginosa showed pattern alterations of the biofilm that can contribute to biofilm resistance and survival. These observations provide evidence for the involvement of bacterial proteolytic activity and LPS profile in the resistance of biofilm bacteria to antibiotics compared to their planktonic counterparts.Keywords: biofilm, Pseudomonas aeruginosa, Staphylococcus aureus, proteolytic activity, lipopolysaccharide

  14. Enhancement of the antibiotic activity of erythromycin by volatile compounds of Lippia alba (Mill.) N.E. Brown against Staphylococcus aureus

    Science.gov (United States)

    Veras, Helenicy N. H.; Campos, Adriana R.; Rodrigues, Fabíola F. G.; Botelho, Marco A.; Coutinho, Henrique D. M.; Menezes, Irwin R. A.; da Costa, José Galberto M.

    2011-01-01

    Background: Lippia alba (Mill.) N.E. Brown, popularly known as “erva-cidreira,” is commonly found in northeastern Brazil. The leaves tea is used to treat digestive disturbances, nausea, cough, and bronchitis. Objective: This work reports the chemical composition and erythromycin-modifying activity by gaseous contact against Staphylococcus aureus. Materials and Methods: The leaves of L. alba were subjected to hydrodistillation, and the essential oil extracted was examined with respect to the chemical composition, by gas chromatography-mass spectrometry (GC-MS), and the essential oil extracted was evaluated for antibacterial and antibiotic-modifying activity by gaseous contact. Results: The overall yield of essential oil obtained by hydrodistillation was 0.52%. The GC-MS analysis has led to the identification of the main components: geranial (31.4%) and neral (29.5%). It was verified that the essential oil interfered with erythromycin antibiotic activity against S. aureus ATCC 25923 was enhanced (221.4%) in the presence of 12% essential oil. The 3% essential oil increased the effect against S. aureus ATCC 25923 (41.6%) and S. aureus ATCC 6538 (58.3%). Conclusion: The essential oil of L. alba influences the activity of erythromycin and may be used as an adjuvant in antibiotic therapy against respiratory tract bacterial pathogens. Conclusion: The essential oil of L. alba influences the activity of erythromycin and may be used as an adjuvant in antibiotic therapy against respiratory tract bacterial pathogens. PMID:22262937

  15. Association between the introduction of a new cystic fibrosis inhaled antibiotic class and change in prevalence of patients receiving multiple inhaled antibiotic classes.

    Science.gov (United States)

    Dasenbrook, Elliott C; Konstan, Michael W; VanDevanter, Donald R

    2015-05-01

    In 2010, aztreonam for inhalation solution joined aminoglycosides and colistimethate as a new cystic fibrosis (CF) chronic inhaled antimicrobial therapy. We studied how the introduction of this new inhaled antibiotic class changed the management of US CF patients. The use of inhaled aminoglycosides, colistimethate, and aztreonam among patients followed in the CF Foundation Patient Registry was analyzed by age group, lung disease stage, and microbiologic status both annually, and at individual visits between 2009 and 2012. The overall prevalence of inhaled antibiotic use did not change during the period, but the prevalence of annual and any visit treatment with >1 inhaled antibiotic class more than doubled. Adults, those with advanced lung disease, and those with >1 Pseudomonas aeruginosa respiratory culture were more likely to receive >1 antibiotic class. Inhaled antibiotic management of US CF patients has dramatically changed in association with the introduction of a third inhaled antibiotic class. Copyright © 2014 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  16. Identification of aac(2')-I type b aminoglycoside-modifying enzyme genes in resistant Acinetobacter baumannii.

    Science.gov (United States)

    Lin, T; Tang, C G; Li, Q H; Ji, J; Ge, H Y; Zhang, X Y; Sun, H P

    2015-03-13

    The aim of this study was to investigate the mechanism underlying the drug resistance of Acinetobacter baumannii toward aminoglycosides. A total of 32 A. baumannii strains were identified by molecular identification and subsequently isolated. The isolates were then amplified by polymerase chain reaction to analyze the 9 aminoglycoside-modifying enzyme genes and 7 16S rRNA methylase genes. Five types of aminoglycoside-modifying enzyme genes and 1 type of 16S rRNA methylase gene were detected in the 32 drug-resistant A. baumannii strains. Positive genes included 7 detection modes, of which the all-6-gene-positive mode aac(2')-Ib+aac(3)-I+aac(6')-Ib+ant(3'')-I+aph(3')-I+armA exhibited the largest number of strains (12, 37.5%). The resistance of A. baumannii against aminoglycosides resulted from the presence of 5 types of aminoglycoside-modifying enzyme genes and the 16S rRNA methylase gene armA. This study is the first to isolate the aac(2')-Ib aminoglycoside-modifying enzyme gene from A. baumannii in a domestic clinical setting.

  17. Identification of a small molecule inhibitor of the aminoglycoside 6'-N-acetyltransferase type ib [AAC(6')-ib] using mixture-based combinatorial libraries.

    Science.gov (United States)

    Tran, Tung; Chiem, Kevin; Jani, Saumya; Arivett, Brock A; Lin, David L; Lad, Rupali; Jimenez, Verónica; Farone, Mary B; Debevec, Ginamarie; Santos, Radleigh; Giulianotti, Marc; Pinilla, Clemencia; Tolmasky, Marcelo E

    2018-02-01

    The aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] is the most widely distributed enzyme among AAC(6')-I-producing Gram-negative pathogens and confers resistance to clinically relevant aminoglycosides including amikacin. This enzyme is therefore ideal to target with enzymatic inhibitors that could overcome resistance to aminoglycosides. The search for inhibitors was carried out using mixture-based combinatorial libraries, the scaffold ranking approach, and the positional scanning strategy. A library with high inhibitory activity had pyrrolidine pentamine scaffold and was selected for further analysis. This library contained 738,192 compounds with functionalities derived from 26 different amino acids (R1, R2 and R3) and 42 different carboxylic acids (R4) in four R group functionalities. The most active compounds all contained S-phenyl (R1 and R3) and S-hydromethyl (R2) functionalities at three locations and differed at the R4 position. The compound containing 3-phenylbutyl at R4 (compound 206) was a robust enzymatic inhibitor in vitro, in combination with amikacin potentiated the inhibition of growth of three resistant bacteria in culture, and improved survival when used as treatment of Galleria mellonella infected with aac(6')-Ib-harboring Klebsiella pneumoniae and Acinetobacter baumannii strains. Copyright © 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  18. Specific binding of nisin to the peptidoglycan precursor lipid II combines pore formation and inhibition of cell wall biosynthesis for potent antibiotic activity

    NARCIS (Netherlands)

    Wiedemann, [No Value; Breukink, E; van Kraaij, C; Kuipers, O.P.; Bierbaum, G; de Kruijff, B; Sahl, HA

    2001-01-01

    Unlike numerous pore-forming amphiphilic peptide antibiotics, the lantibiotic nisin is active in nanomolar concentrations, which results from its ability to use the Lipid-bound cell wall precursor lipid II as a docking molecule for subsequent pore formation. Here we use genetically engineered nisin

  19. Predictive Value of Prior Colonization and Antibiotic Use for Third-Generation Cephalosporin-Resistant Enterobacteriaceae Bacteremia in Patients With Sepsis

    NARCIS (Netherlands)

    Rottier, Wouter C.; Bamberg, Yara R. P.; Dorigo-Zetsma, J. Wendelien; van der Linden, Paul D.; Ammerlaan, Heidi S. M.; Bonten, Marc J. M.

    2015-01-01

    Background. To prevent inappropriate empiric antibiotic treatment in patients with bacteremia caused by third-generation cephalosporin (3GC)-resistant Enterobacteriaceae (3GC-R EB), Dutch guidelines recommend beta-lactam and aminoglycoside combination therapy or carbapenem monotherapy in patients

  20. Evaluation of Antibacterial Activity of Aqueous Extracts of Onion and some Antibiotics on a Number of Important Bacteria in Terms of Food Hygiene

    Directory of Open Access Journals (Sweden)

    Anzabi Younes

    2014-10-01

    Full Text Available Objective: The purpose of this study was to evaluate the antibacterial effect of edible onion plant and a number of common antibiotics in the case of some important bacteria regarding food hygiene. Materials and Methods: The sensitivity or resistance of standard strains of 9 important species of transmissible pathogenic bacteria, through food in laboratory Mueller Hinton agar medium and using blank paper discs containing onion extract, 9 standard synthetic chemicals, and antibiotics by agar disk diffusion method (disk diffusion agar, were investigated. Results: The findings of this study showed that, of the 9 species of bacteria tested, the aqueous extract of onion only has relatively small antibacterial activity on the 2 species of Staphylococcus aureus and clostridium perfringens. Statistical analysis of the results also indicated that there was no significant relationship among the different antibiotics used and the edible onion aqueous extract, and the resistance or susceptibility of isolates. Moreover, there was a difference between different antibiotics tested in this study and aqueous extract of onion, regarding the number of resistant bacteria, and intermediate and moderate susceptibility, and susceptibility to the antibacterial compounds. Conclusion: It seems that the aqueous extract of onions cannot be used as an alternative to commonly used antibiotics to fight important bacteria in terms food hygiene.

  1. Antibiotic Safety

    Science.gov (United States)

    ... Antibiotics www.healthsci.tufts.edu Georgia-Pacific Health Smart Institute www.gphealthsmart.com Special thanks to Rhonda ... effectiveness of other medications such as birth control pills? 7. Are there any possible adverse reactions if ...

  2. Medical-grade honey enriched with antimicrobial peptides has enhanced activity against antibiotic-resistant pathogens

    NARCIS (Netherlands)

    Kwakman, P.H.S.; Boer, den L.; Ruyter-Spira, C.; Creemers-Molenaar, T.; Helsper, J.P.F.G.; Vandenbroucke-Grauls, C.M.J.E.; Zaat, S.A.J.; Velde, te A.A.

    2011-01-01

    Honey has potent activity against both antibioticsensitive and -resistant bacteria, and is an interesting agent for topical antimicrobial application to wounds. As honey is diluted by wound exudate, rapid bactericidal activity up to high dilution is a prerequisite for its successful application. We

  3. Studying the Phenotypic and Genotypic Expression of Antibiotic Resistance in Campylobacter jejuni under Stress Conditions.

    Science.gov (United States)

    Efimochkina, N R; Stetsenko, V V; Bykova, I V; Markova, Yu M; Polyanina, A S; Aleshkina, A I; Sheveleva, S A

    2018-03-01

    Specific features for the development of resistance in Campylobacter jejuni strains were studied after treatment with antibiotics of 6 pharmacological groups. Populations of 18 native strains of C. jejuni (isolated from raw poultry products) and their subcultures (obtained after 2-3-fold stress exposures to antimicrobial agents in subinhibitory doses) were examined to evaluate the expression of phenotypic antibiotic resistance. Genotypic properties of strains were studied by the PCR with primers that detect the presence of genes for resistance to aminoglycosides (aphA-1, aphA-3, and aphA-7), tetracyclines (tetO), and quinolones (GZgyrA). The majority of test strains of C. jejuni exhibited a high resistance to nalidixic acid, ciprofloxacin, and tetracycline, which reached the maximum value after numerous passages. The expression of antibiotic resistance was greatest in the presence of nalidixic acid and tetracycline. Ciprofloxacin resistance of 33% strains, which were initially resistant to this antibiotic, was increased after 2-3-fold treatment. We revealed a high degree of correspondence between phenotypic and genotypic profiles of antibiotic resistance in food isolates of Campylobacter. One, two, or more genes of aphA were identified in 85% strains phenotypically resistant to aminoglycosides. The tetO gene was found nearly in all strains resistant to tetracycline. Studying the biofilm matrix in C. jejuni after culturing with antibiotics in subinhibitory doses showed that quinolones (particularly nalidixic acid) and tetracyclines potentiate the formation of biofilms and increase the tolerance of Campylobacter to stress exposures. The intensity of biofilm growth was shown to depend little on the effect of macrolides and aminoglycosides. Therefore, the presence of these agents in residual concentrations is associated with a lower risk for the development of antibiotic resistance in C. jejuni populations.

  4. The effect of systemic antibiotics administered during the active phase of non-surgical periodontal therapy or after the healing phase: a systematic review

    Science.gov (United States)

    FRITOLI, Aretuza; GONÇALVES, Cristiane; FAVERI, Marcelo; FIGUEIREDO, Luciene Cristina; PÉREZ-CHAPARRO, Paula Juliana; FERMIANO, Daiane; FERES, Magda

    2015-01-01

    Objective The aim of this systematic review was to compare the clinical effectiveness of systemic antibiotics administered in the active stage of periodontal treatment or after the healing phase. Material and Methods An electronic search was performed in the databases EMBASE, MEDLINE and Cochrane Central Register of Controlled Trials (CENTRAL), in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. A manual search of the reference list of selected studies and of review articles was also performed up to November 2013. Randomized Clinical Trials (RCT) that evaluated the systemic administration of antibiotics as adjuvants to scaling and root planning (SRP) at different phases of periodontal treatment were included. Systematic reviews and studies that evaluated subjects with systemic diseases and those that used subantimicrobial doses of antibiotics were excluded. Results The initial search identified 1,039 articles, of which seven were selected, and only one met the inclusion criteria. This study showed that subjects taking metronidazole and amoxicillin at the initial phase of treatment exhibited statistically significantly greater reduction in pocket depth and gain in clinical attachment level in initially deep sites (PD≥7 mm) than subjects taking antibiotics after healing (pantibiotic intake, at the healing phase. Conclusion To date, only one short-term RCT has directly compared different moments of systemic antibiotics administration, as adjuncts to SRP, in the treatment of periodontitis. Although the results of this study suggested some benefits for antibiotics intake during the active phase of therapy, these findings need to be confirmed by larger placebo-controlled randomized clinical trials with longer follow-up periods. PMID:26221918

  5. Antibacterial activity of epigallocatechin-3-gallate (EGCG) and its synergism with β-lactam antibiotics sensitizing carbapenem-associated multidrug resistant clinical isolates of Acinetobacter baumannii.

    Science.gov (United States)

    Lee, Spencer; Razqan, Ghaida Saleh Al; Kwon, Dong H

    2017-01-15

    Infections caused by Acinetobacter baumannii were responsive to conventional antibiotic therapy. However, recently, carbapenem-associated multidrug resistant isolates have been reported worldwide and present a major therapeutic challenge. Epigallocatechin-3-Gallate (EGCG) extracted from green tea exhibits antibacterial activity. We evaluated the antibacterial activity of EGCG and possible synergism with antibiotics in carbapenem-associated multidrug resistant A. baumannii. A potential mechanism for synergism was also explored. Seventy clinical isolates of A. baumannii collected from geographically different areas were analyzed by minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of EGCG. Checkerboard and time-killing assays were performed to exam the synergism between EGCG and antibiotics. The effects of EGCG on a multidrug efflux pump inhibitor (1-[1-naphthylmethyl] piperazine; NMP) and β-lactamase production were also examined in A. baumannii. Sixty-three of 70 clinical isolates of A. baumannii carried carbapenemase-encoding genes with carbapenem-associated multidrug resistance. Levels of MIC and MBC of EGCG ranged from 64 to 512µg/ml and from 128 to ≥1024µg/ml, respectively among the clinical isolates. MIC 90 and MBC 86 levels were 256µg/ml and 512µg/ml of EGCG, respectively. Subinhibitory concentration of EGCG in combination with all antibiotics tested, including carbapenem, sensitized (MICs fall≤1.0µg/ml) all carbapenem-associated multidrug resistant isolates. Checkerboard and time-killing assays showed synergism between EGCG and meropenem (or carbenicillin) counted as fractional inhibitory concentration of 2log10 within 12h, respectively. EGCG significantly increased the effect of NMP but was unrelated to β-lactamase production in A. baumannii, suggesting EGCG may be associated with inhibition of efflux pumps. Overall we suggest that EGCG-antibiotic combinations might provide an alternative approach to treat

  6. Andrographolide: A potent antituberculosis compound that targets Aminoglycoside 2'-N-acetyltransferase in Mycobacterium tuberculosis.

    Science.gov (United States)

    Prabu, Amudha; Hassan, Sameer; Prabuseenivasan; Shainaba, A S; Hanna, L E; Kumar, Vanaja

    2015-09-01

    Tuberculosis (TB) still remains a major challenging infectious disease. The increased rate of emergence of multi-drug resistant and extensively-drug resistant strains of the organism has further complicated the situation, resulting in an urgent need for new anti-TB drugs. Antimycobacterial activity of Andrographis paniculata was evaluated using a rapid LRP assay and the probable targets were identified by docking analysis. The methanolic extract of A. paniculata showed maximum antimycobacterial activity at 250μg/ml against all the tested strains of M. tuberculosis (H37Rv, MDR, and drug sensitive). Based on bioassay guided fractionation, andrographolide was identified as the potent molecule. With the docking analysis, both ICDH (Isocitrate Dehydrogenase) and AAC (Aminoglycoside 2'-N-acetyltransferase) were predicted as targets of andrographolide in M. tuberculosis. Molecular simulation revealed that, ICDH showed low binding affinity to andrographolide. However, for AAC, the andrographolide was observed to be well within the active site after 10ns of molecular simulation. This suggests that ACC (PDB ID 1M4I) could be the probable target for andrographolide. Copyright © 2015 Elsevier Inc. All rights reserved.

  7. Enhanced simultaneous PEC eradication of bacteria and antibiotics by facilely fabricated high-activity {001} facets TiO2 mounted onto TiO2 nanotubular photoanode.

    Science.gov (United States)

    Li, Guiying; Nie, Xin; Chen, Jiangyao; Wong, Po Keung; An, Taicheng; Yamashita, Hiromi; Zhao, Huijun

    2016-09-15

    Biohazards and coexisted antibiotics are two groups of emerging contaminants presented in various aquatic environments. They can pose serious threat to the ecosystem and human health. As a result, inactivation of biohazards, degradation of antibiotics, and simultaneous removal of them are highly desired. In this work, a novel photoanode with a hierarchical structured {001} facets exposed nano-size single crystals (NSC) TiO2 top layer and a perpendicularly aligned TiO2 nanotube array (NTA) bottom layer (NSC/NTA) was successfully fabricated. The morphology and facets of anatase TiO2 nanoparticles covered on the top of NTA layer could be controlled by adjusting precalcination temperature and heating rate as the pure NTA was clamped with glasses. Appropriate recalcination can timely remove surface F from {001} facets, and the photocatalytic activity of the resultant photoanode was subsequently activated. NSC/NTA photoanode fabricated under 500 °C precalcination with 20 °C min(-1) followed by 550 °C recalcination possessed highest photoelectrocatalytic efficiency to simultaneously remove bacteria and antibiotics. Results suggest that two-step calcination is necessary for fabrication of high photocatalytic activity NSC/NTA photoanode. The capability of simultaneous eradication of bacteria and antibiotics shows great potential for development of a versatile approach to effectively purify various wastewaters contaminated with complex pollutants. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Acetylcholinesterase activity as a biomarker of exposure to antibiotics and pesticides in the black tiger shrimp (Penaeus monodon).

    Science.gov (United States)

    Tu, Huynh Thi; Silvestre, Frederic; Scippo, Marie-Louise; Thome, Jean-Pierre; Phuong, Nguyen Thanh; Kestemont, Patrick

    2009-07-01

    This study aimed to assess the potentiality to use cholinesterase activity (ChE) in black tiger shrimp (Penaeus monodon) as a biomarker of exposure to 2 antibiotics (enrofloxacin, furazolidone) and 2 pesticides (endosulfan, deltamethrin), commonly used in Vietnamese farms. ChE from muscle and gills was first characterised using three different substrates and specific inhibitors. Results showed that both tissues possess only one ChE which displays the typical properties of an acetylcholinesterase (AChE). In a second part, shrimp (average weight of 8.8-10 g) were fed with medicated-feed containing 4g enrofloxacin (quinolone) or furazolidone (nitrofuran)/kg for 7 days, or exposed to 3 actual concentrations of endosulfan (0, 0.009, 0.09, 0.9 microg/L) or deltamethrin (0, 0.0007, 0.007, 0.07 microg/L) for 4 days. After treatment, animals were decontaminated during 7 days. We observed that AChE activity in muscle was not significantly affected in shrimp fed with enrofloxacin or furazolidone, while it significantly decreased (up to 28%) in gills of shrimp fed with furazolidone. Following endosulfan and deltamethrin exposure, no significant changes in AChE activity were observed in gills. However, a significant decrease occurred in muscle after 4 days exposure (inhibition of 30% and 49% at 0.9 microg/L endosulfan and 0.07 microg/L deltamethrin, respectively). While muscle AChE activity should be assessed to point out endosulfan or deltamethrin exposure, gill AChE activity impairment could indicate an exposure to furazolidone. The present study underlines the benefits to use AChE as a biomarker of chemotherapeutics as part of an integrated aquaculture management to reach industry sustainability.

  9. Design at the atomic level: design of biaryloxazolidinones as potent orally active antibiotics.

    Science.gov (United States)

    Zhou, Jiacheng; Bhattacharjee, Ashoke; Chen, Shili; Chen, Yi; Duffy, Erin; Farmer, Jay; Goldberg, Joel; Hanselmann, Roger; Ippolito, Joseph A; Lou, Rongliang; Orbin, Alia; Oyelere, Ayomi; Salvino, Joe; Springer, Dane; Tran, Jennifer; Wang, Deping; Wu, Yusheng; Johnson, Graham

    2008-12-01

    We have developed a first generation of hybrid sparsomycin-linezolid compounds into a new family of orally bioavailable biaryloxazolidinones that have activity against both linezolid-susceptible and -resistant gram-positive bacteria as well as the fastidious gram-negative bacteria Haemophilus influenzae and Moraxella catarrahalis. The convergent synthesis of these new compounds is detailed.

  10. Environmental cycle of antibiotic resistance encoded genes: A systematic review

    Directory of Open Access Journals (Sweden)

    R. ghanbari

    2017-12-01

    Full Text Available Antibiotic-resistant bacteria and genes enter the environment in different ways. The release of these factors into the environment has increased concerns related to public health. The aim of the study was to evaluate the antibiotic resistance genes (ARGs in the environmental resources. In this systematic review, the data were extracted from valid sources of information including ScienceDirect, PubMed, Google Scholar and SID. Evaluation and selection of articles were conducted on the basis of the PRISMA checklist. A total of 39 articles were included in the study, which were chosen from a total of 1249 papers. The inclusion criterion was the identification of genes encoding antibiotic resistance against the eight important groups of antibiotics determined by using the PCR technique in the environmental sources including municipal and hospital wastewater treatment plants, animal and agricultural wastes, effluents from treatment plants, natural waters, sediments, and drinking waters. In this study, 113 genes encoding antibiotic resistance to eight groups of antibiotics (beta-lactams, aminoglycosides, tetracyclines, macrolides, sulfonamides, chloramphenicol, glycopeptides and quinolones were identified in various environments. Antibiotic resistance genes were found in all the investigated environments. The investigation of microorganisms carrying these genes shows that most of the bacteria especially gram-negative bacteria are effective in the acquisition and the dissemination of these pollutants in the environment. Discharging the raw wastewaters and effluents from wastewater treatments acts as major routes in the dissemination of ARGs into environment sources and can pose hazards to public health.

  11. Antimicrobial activity of biopolymer–antibiotic thin films fabricated by advanced pulsed laser methods

    International Nuclear Information System (INIS)

    Cristescu, R.; Popescu, C.; Dorcioman, G.; Miroiu, F.M.; Socol, G.; Mihailescu, I.N.; Gittard, S.D.; Miller, P.R.; Narayan, R.J.; Enculescu, M.; Chrisey, D.B.

    2013-01-01

    We report on thin film deposition by matrix assisted pulsed laser evaporation (MAPLE) of two polymer–drug composite thin film systems. A pulsed KrF* excimer laser source (λ = 248 nm, τ = 25 ns, ν = 10 Hz) was used to deposit composite thin films of poly(D,L-lactide) (PDLLA) containing several gentamicin concentrations. FTIR spectroscopy was used to demonstrate that MAPLE-transferred materials exhibited chemical structures similar to those of drop cast materials. Scanning electron microscopy data indicated that MAPLE may be used to fabricate thin films of good morphological quality. The activity of PDLLA–gentamicin composite thin films against Staphylococcus aureus bacteria was demonstrated using drop testing. The influence of drug concentration on microbial viability was also assessed. Our studies indicate that polymer–drug composite thin films prepared by MAPLE may be used to impart antimicrobial activity to implants, medical devices, and other contact surfaces.

  12. Antimicrobial activity, antibiotic susceptibility and virulence factors of Lactic Acid Bacteria of aquatic origin intended for use as probiotics in aquaculture

    Science.gov (United States)

    2013-01-01

    Background The microorganisms intended for use as probiotics in aquaculture should exert antimicrobial activity and be regarded as safe not only for the aquatic hosts but also for their surrounding environments and humans. The objective of this work was to investigate the antimicrobial/bacteriocin activity against fish pathogens, the antibiotic susceptibility, and the prevalence of virulence factors and detrimental enzymatic activities in 99 Lactic Acid Bacteria (LAB) (59 enterococci and 40 non-enterococci) isolated from aquatic animals regarded as human food. Results These LAB displayed a broad antimicrobial/bacteriocin activity against the main Gram-positive and Gram-negative fish pathogens. However, particular safety concerns based on antibiotic resistance and virulence factors were identified in the genus Enterococcus (86%) (Enterococcus faecalis, 100%; E. faecium, 79%). Antibiotic resistance was also found in the genera Weissella (60%), Pediococcus (44%), Lactobacillus (33%), but not in leuconostocs and lactococci. Antibiotic resistance genes were found in 7.5% of the non-enterococci, including the genera Pediococcus (12.5%) and Weissella (6.7%). One strain of both Pediococcus pentosaceus and Weissella cibaria carried the erythromycin resistance gene mef(A/E), and another two P. pentosaceus strains harboured lnu(A) conferring resistance to lincosamides. Gelatinase activity was found in E. faecalis and E. faecium (71 and 11%, respectively), while a low number of E. faecalis (5%) and none E. faecium exerted hemolytic activity. None enterococci and non-enterococci showed bile deconjugation and mucin degradation abilities, or other detrimental enzymatic activities. Conclusions To our knowledge, this is the first description of mef(A/E) in the genera Pediococcus and Weissella, and lnu(A) in the genus Pediococcus. The in vitro subtractive screening presented in this work constitutes a valuable strategy for the large-scale preliminary selection of putatively safe LAB

  13. Practices and Factors Influencing the Use of Antibiotics in Selected Poultry Farms in Ghana

    DEFF Research Database (Denmark)

    Boamah, VE; Odoi, H; Dalsgaard, Anders

    2016-01-01

    and to assess factors influencing farmers’ choice of antibiotics for use on their farms. A cross-sectional survey using questionnaires and semistructured interviews was conducted among 400 poultry farms in the Ashanti, Brong-Ahafo and Greater Accra regions of Ghana. Data was analysed using IBM SPSS...... and Microsoft Excel. Multivariate analyses were used to evaluate correlations between farm variables and the dependency of antibiotic use on internal and external farm characteristics. Farmers reported the use of 35 different antimicrobial agents for management of conditions such as Newcastle, fowl pox......, coccidiosis, and coryza. From these agents, 20 essential antibiotics belonging to 10 antibiotic classes were extracted. Frequently employed antibiotics were tetracyclines (24.17%), aminoglycosides (17.87%), penicillins (16.51%) and fluoroquinolones (10.55%). Only 63% of the farms completed recommended...

  14. Antibiotics in late clinical development.

    Science.gov (United States)

    Fernandes, Prabhavathi; Martens, Evan

    2017-06-01

    Most pharmaceutical companies have stopped or have severely limited investments to discover and develop new antibiotics to treat the increasing prevalence of infections caused by multi-drug resistant bacteria, because the return on investment has been mostly negative for antibiotics that received marketing approved in the last few decades. In contrast, a few small companies have taken on this challenge and are developing new antibiotics. This review describes those antibiotics in late-stage clinical development. Most of them belong to existing antibiotic classes and a few with a narrow spectrum of activity are novel compounds directed against novel targets. The reasons for some of the past failures to find new molecules and a path forward to help attract investments to fund discovery of new antibiotics are described. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Tetracycline Antibiotics and Resistance.

    Science.gov (United States)

    Grossman, Trudy H

    2016-04-01

    Tetracyclines possess many properties considered ideal for antibiotic drugs, including activity against Gram-positive and -negative pathogens, proven clinical safety, acceptable tolerability, and the availability of intravenous (IV) and oral formulations for most members of the class. As with all antibiotic classes, the antimicrobial activities of tetracyclines are subject to both class-specific and intrinsic antibiotic-resistance mechanisms. Since the discovery of the first tetracyclines more than 60 years ago, ongoing optimization of the core scaffold has produced tetracyclines in clinical use and development that are capable of thwarting many of these resistance mechanisms. New chemistry approaches have enabled the creation of synthetic derivatives with improved in vitro potency and in vivo efficacy, ensuring that the full potential of the class can be explored for use against current and emerging multidrug-resistant (MDR) pathogens, including carbapenem-resistant Enterobacteriaceae, MDR Acinetobacter species, and Pseudomonas aeruginosa. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  16. Antibiotic allergy.

    Science.gov (United States)

    Caimmi, S; Caimmi, D; Lombardi, E; Crisafulli, G; Franceschini, F; Ricci, G; Marseglia, G L

    2011-01-01

    Antibiotics are commonly injected during the perioperative period and are responsible of 15 percent of the anaphylactic reactions. Anaphylaxis triggered by antibiotics primarily involves penicillin and cephalosporin. The management of patients with histories of allergic reactions to antibiotics is a common situation in clinical practice. The confirmation or invalidation of the allergic nature of the reported reaction is not based on in vitro tests, but on a rigorous allergological work-up based on detailed analysis of clinical history, skin tests and drug provocation test. Considering a possible cross-reactivity between penicillins, once an immediate penicillin allergy has been diagnosed, skin testing with the alternative molecule (cephalosporin, carbapenem, aztreonam) is mandatory and, if negative, the relevant drug should be given in an appropriate setting at increasing doses.

  17. Inhibition of Lipid A Biosynthesis as the Primary Mechanism of CHIR-090 Antibiotic Activity in Escherichia coli

    Science.gov (United States)

    Barb, Adam W.; McClerren, Amanda L.; Snehelatha, Karnem; Reynolds, C. Michael; Zhou, Pei; Raetz, Christian R.H.

    2009-01-01

    The deacetylation of UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine (UDP-3-O-acyl-GlcNAc) by LpxC is the committed reaction of lipid A biosynthesis. CHIR-090, a novel N-aroyl-l-threonine hydroxamic acid, is a potent, slow, tight-binding inhibitor of the LpxC deacetylase from the hyperthermophile Aquifex aeolicus, and it has excellent antibiotic activity against P. aeruginosa and E. coli, as judged by disk diffusion assays. We now report that CHIR-090 is also a two-step slow, tight-binding inhibitor of Escherichia coli LpxC with Ki = 4.0 nM, Ki* = 0.5 nM, k5 = 1.9 min-1 and k6 = 0.18 min-1. CHIR-090 at low nM levels inhibits LpxC orthologues from diverse Gram-negative pathogens, including Pseudomonas aeruginosa, Neisseria meningitidis, and Helicobacter pylori. In contrast, CHIR-090 is a relatively weak competitive and conventional inhibitor (lacking slow, tight-binding kinetics) of LpxC from Rhizobium leguminosarum (Ki = 340 nM), a Gram-negative plant endosymbiont that is resistant to this compound. The KM (4.8 μM) and the kcat (1.7 s-1) of R. leguminosarum LpxC with UDP-3-O-(R-3-hydroxymyristoyl)-N-acetylglucosamine as the substrate are similar to values reported for E. coli LpxC. R. leguminosarum LpxC therefore provides a useful control for validating LpxC as the primary target of CHIR-090 in vivo. An E. coli construct in which the chromosomal lpxC gene is replaced by R. leguminosarum lpxC is resistant to CHIR-090 up to 100 μg/mL, or 400 times above the minimal inhibitory concentration for wild-type E. coli. Given its relatively broad spectrum and potency against diverse Gram-negative pathogens, CHIR-090 is an excellent lead for the further development of new antibiotics targeting the lipid A pathway. PMID:17335290

  18. Prevalence, species differentiation, haemolytic activity, and antibiotic susceptibility of aeromonads in untreated well water

    Directory of Open Access Journals (Sweden)

    Khalifa Sifaw Ghenghesh

    2001-02-01

    Full Text Available The use of untreated water for drinking and other activities have been associated with intestinal and extraintestinal infections in humans due to Aeromonas species. In the present study aeromonads were isolated from 48.7% of 1,000 water samples obtained from wells and other miscellaneous sources. Aeromonas species were detected in 45% of samples tested in spring, 34.5% in summer, 48% in autumn and 60% of samples tested in winter. Speciation of 382 strains resulted in 225 (59% being A. hydrophila, 103 (27% A. caviae, 42 (11% A. sobria and 11 (3% atypical aeromonads. Of 171 Aeromonas strains tested for their haemolytic activity, 53%, 49%, 40% and 37% were positive in this assay using human, horse, sheep and camel erythrocytes respectively. The results obtained indicate that potentially enteropathogenic Aeromonas species are commonly present in untreated drinking water obtained from wells in Libya (this may also apply to other neighbouring countries which may pose a health problem to users of such water supplies. In addition, ceftriaxone and ciprofloxacin are suitable drugs that can be used in the treatment of Aeromonas-associated infections, particularly in the immunocompromised, resulting from contact with untreated sources of water.

  19. Spectroscopic, semiempirical studies and antibacterial activity of new urethane derivatives of natural polyether antibiotic - Monensin A

    Science.gov (United States)

    Huczyński, Adam; Stefańska, Joanna; Piśmienny, Mieszko; Brzezinski, Bogumil

    2013-02-01

    A series of new Monensin A dimers linked by diurethane moiety were synthesised and their molecular structures were studied using ESI-MS, FT-IR, 1H and 13C NMR and PM5 methods. The results showed that the compounds form a pseudo-cyclic structure stabilized by three intramolecular hydrogen bonds and the sodium cation was coordinated by five oxygen atoms of polyether skeleton of Monensin moiety. The NMR and FT-IR data of complexes of Monensin urethane sodium salts demonstrated that within the pseudo-cyclic structure the carbonyl oxygen atom of the urethane group did not coordinate the sodium cation. Monensin urethanes were tested in vitro for the activity against Gram-positive and Gram-negative bacteria and fungi as well as against a series of clinical isolates of Staphylococcus: methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-sensitive S. aureus (MSSA). The most active compound against MRSA and MSSA was 1,4-phenylene diurethane of Monensin with MIC 10.4-41.4 μmol/L).

  20. Antimicrobial Activities of a Plethora of Medicinal Plant Extracts and Hydrolates against Human Pathogens and Their Potential to Reverse Antibiotic Resistance

    Directory of Open Access Journals (Sweden)

    Dieudonné Lemuh Njimoh

    2015-01-01

    Full Text Available Microbial infections till date remain a scourge of humanity due to lack of vaccine against some infections, emergence of drug resistant phenotypes, and the resurgence of infections amongst others. Continuous quest for novel therapeutic approaches remains imperative. Here we (i assessed the effects of extracts/hydrolates of some medicinal plants on pathogenic microorganisms and (ii evaluated the inhibitory potential of the most active ones in combination with antibiotics. Extract E03 had the highest DZI (25 mm. Extracts E05 and E06 were active against all microorganisms tested. The MICs and MBCs of the methanol extracts ranged from 16.667 × 103 μg/mL to 2 μg/mL and hydrolates from 0.028 to 333333 ppm. Extract E30 had the highest activity especially against S. saprophyticus (MIC of 6 ppm and E. coli (MIC of 17 ppm. Combination with conventional antibiotics was shown to overcome resistance especially with E30. Analyses of the extracts revealed the presence of alkaloids, flavonoids, triterpenes, steroids, phenols, and saponins. These results justify the use of these plants in traditional medicine and the practice of supplementing decoctions/concoctions with conventional antibiotics. Nauclea pobeguinii (E30, the most active and synergistic of all these extracts, and some hydrolates with antimicrobial activity need further exploration for the development of novel antimicrobials.

  1. The Antibiotic Resistance Problem Revisited

    Science.gov (United States)

    Lawson, Michael A.

    2008-01-01

    The term "antibiotic" was first proposed by Vuillemin in 1889 but was first used in the current sense by Walksman in 1941. An antibiotic is defined as a "derivative produced by the metabolism of microorganisms that possess antibacterial activity at low concentrations and is not toxic to the host." In this article, the author describes how…

  2. Factors associated with the determination of antibiotic activity in bovine semen.

    Science.gov (United States)

    Truscott, R B

    1983-10-01

    Rosaramicin, an agent shown to be effective in vitro against ureaplasma of bovine origin was tested as an additive to bovine semen extender. Although some reduction in semen quality occurred it was still deemed satisfactory for use. In a test involving 41 cows inseminated once at estrus with rosaramicin-treated semen (162 mcg/mL) the nonreturn rate was 24% compared to a calculated average for this semen of 63% (n = 3310). The effect of centrifugation, time and temperature was examined in vitro using a combination of 150 mcg of lincomycin, 300 mcg of spectinomycin and 450 mcg of tylosin against ten strains of bovine ureaplasma. This combination has ureaplasmacidal activity and is suggested as an additive to semen extenders for the control of ureaplasma.

  3. Synergistic activity of coriander oil and conventional antibiotics against Acinetobacter baumannii.

    Science.gov (United States)

    Duarte, A; Ferreira, S; Silva, F; Domingues, F C

    2012-02-15

    In this study we investigated the existence of synergistic antibacterial effect between coriander (Coriandrum sativum L.) essential oil and six different antibacterial drugs (cefoperazone, chloramphenicol, ciprofloxacin, gentamicin, tetracycline and piperacillin). The antibacterial activity of coriander oil was assessed using microdilution susceptibility testing and synergistic interaction by checkerboard assays. The association of coriander essential oil with chloramphenicol, ciprofloxacin, gentamicin and tetracycline against Acinetobacter baumannii showed in vitro effectiveness, which is an indicator of a possible synergistic interaction against two reference strains of A. baumannii (LMG 1025 and LMG 1041) (FIC index from 0.047 to 0.375). However, when tested the involvement between coriander essential oil and piperacillin or cefoperazone, the isobolograms and FIC index showed an additive interaction. The in vitro interaction could improve the antimicrobial effectiveness of ciprofloxacin, gentamicin and tetracycline and may contribute to resensitize A. baumannii to the action of chloramphenicol. Copyright © 2011 Elsevier GmbH. All rights reserved.

  4. The Antibacterial Activity of Metal Complexes Containing 1,10- phenanthroline: Potential as Alternative Therapeutics in the Era of Antibiotic Resistance.

    Science.gov (United States)

    Viganor, Livia; Howe, Orla; McCarron, Pauraic; McCann, Malachy; Devereux, Michael

    2017-01-01

    The "antibiotic era", characterized by the overuse and misuse of antibiotics, over the last half-century has culminated in the present critical "era of resistance". The treatment of bacterial infections is challenging because of a decline in the current arsenal of useful antibiotics and the slow rate of new drug development. The discovery of a new gene (mcr-1) in 2015, which enables bacteria to be highly resistant to polymyxins (such as colistin), the last line of antibiotic defence left, heralds a new level of concern as this gene is susceptible to horizontal gene transfer, with alarming potential to be spread between different bacterial populations, suggesting that the progression from "extensive drug resistance" to "pan-drug resistance" may be inevitable. Clearly there is a need for the development of novel classes of anti-bacterial agents capable of killing bacteria through mechanisms that are different to those of the known classes of antibiotics. 1,10-phenanthroline (phen) is a heterocyclic organic compound which exerts in vitro antimicrobial activity against a broad-spectrum of bacteria. The antimicrobial activity of phen can be significantly modulated by modifying its structure. The development of metal-phen complexes offers the medicinal chemist an opportunity to expand such structural diversity by controlling the geometry and varying the oxidation states of the metal