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Sample records for aminoglycoside antibiotic activity

  1. [Determination of the biological activity of aminoglycoside antibiotics on a dry nutrient medium of Soviet manufacture].

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    Grigor'eva, V M; Andreeva, Z M; Astanina, L N; Shiriaeva, V L; Gridneva, N I

    1981-06-01

    Possible use of the dry nutrient medium manufactured in the USSR for the assay of aminoglycoside antibiotic activity with the agar diffusion method was studied. The optimal conditions for the antibiotic activity assay on this medium were developed. The dry nutrient medium may be used for the activity assay of the aminoglycoside antibiotics, i. e. streptomycin sulfate, dihydrostreptomycin sulfate, neomycin sulfate, monomycin and gentamicin sulfate.

  2. Antibiotic Binding Drives Catalytic Activation of Aminoglycoside Kinase APH(2″)-Ia.

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    Caldwell, Shane J; Huang, Yue; Berghuis, Albert M

    2016-06-01

    APH(2″)-Ia is a widely disseminated resistance factor frequently found in clinical isolates of Staphylococcus aureus and pathogenic enterococci, where it is constitutively expressed. APH(2″)-Ia confers high-level resistance to gentamicin and related aminoglycosides through phosphorylation of the antibiotic using guanosine triphosphate (GTP) as phosphate donor. We have determined crystal structures of the APH(2″)-Ia in complex with GTP analogs, guanosine diphosphate, and aminoglycosides. These structures collectively demonstrate that aminoglycoside binding to the GTP-bound kinase drives conformational changes that bring distant regions of the protein into contact. These changes in turn drive a switch of the triphosphate cofactor from an inactive, stabilized conformation to a catalytically competent active conformation. This switch has not been previously reported for antibiotic kinases or for the structurally related eukaryotic protein kinases. This catalytic triphosphate switch presents a means by which the enzyme can curtail wasteful hydrolysis of GTP in the absence of aminoglycosides, providing an evolutionary advantage to this enzyme.

  3. Termite usage associated with antibiotic therapy: enhancement of aminoglycoside antibiotic activity by natural products of Nasutitermes corniger (Motschulsky 1855

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    Almeida-Filho Geraldo G

    2009-09-01

    Full Text Available Abstract Background Several species from Insecta are used as remedies. Among these species, the termite Nasutitermes corniger is commonly used in traditional medicine in Northeast Brazil. The present work tests the modifying antibiotic activity of Nasutitermes corniger, a termite used in folk medicine in Northeastern region of Brazil. Methods Chlorpromazine and decocts of N. corniger were collected from two different plant species used in the traditional medicine were tested for their antimicrobial activity against strains of Escherichia coli resistant to aminoglycosides. The growth of two bacterial strains of E. coli was tested using decocts and chlorpromazine alone or associeted with aminogycosides. Results The MIC and MBC values were ≥1024 μg/ml for both strains of E. coli assayed. A significant synergism was observed between both decocts and chlorpromazine when assyed with neomycin. This synergism with neomycin indicates the involvement of an efflux system in the resistance to this aminoglycoside. Conclusion Therefore it is suggested that natural products from N. corniger could be used as a source of zoo-derived natural products with modifying antibiotic activity to aminoglycosides, being a new weapon against the bacterial resistance to antibiotics.

  4. Cationic Amphiphiles Increase Activity of Aminoglycoside Antibiotic Tobramycin in the Presence of Airway Polyelectrolytes

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    Purdy Drew, Kirstin R.; Sanders, Lori K.; Culumber, Zachary W.; Zribi, Olena; Wong, Gerard C.L.; (UIUC)

    2009-06-17

    It is empirically known that anionic polyelectrolytes present in cystic fibrosis (CF) airways due to bacterial infection significantly decrease the activity of cationic antimicrobials via electrostatic binding. In this work, we use synchrotron small-angle X-ray scattering to investigate the interaction between tobramycin, an aminoglycoside antibiotic commonly administered to CF patients via inhalation, with DNA, which is found in high concentrations in the CF airway. We find that interactions between DNA and tobramycin are significantly modified by the presence of mixtures of amphiphilic molecules. We measure a hierarchy of self-assembled structures formed between tobramycin, DNA, and the amphiphile mixtures and show how interactions between these components can be controlled. Results indicate that mixtures of cationic and negative curvature amphiphiles optimized for DNA binding via charge matching and curvature matching can competitively displace bound tobramycin from DNA and thereby drastically suppress tobramycin-DNA binding and resultant antimicrobial inactivation. Growth inhibition assays confirm the increased activity of tobramycin in the presence of DNA with the addition of the amphiphiles. These results suggest that optimized cationic amphiphile solutions have the potential to enhance antimicrobial function in highly infected environments that contain increased concentrations of anionic inflammatory polymers.

  5. Cationic Amphiphiles Increase Activity of Aminoglycoside Antibiotic Tobramycin in the Presence of Airway Polyelectrolytes

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    Drew, K.R.Purdy; Sanders, L.K.; Culumber, Z.W.; Zribi, O.; Wong, G.C.L.

    2009-05-21

    It is empirically known that anionic polyelectrolytes present in cystic fibrosis (CF) airways due to bacterial infection significantly decrease the activity of cationic antimicrobials via electrostatic binding. In this work, we use synchrotron small-angle X-ray scattering to investigate the interaction between tobramycin, an aminoglycoside antibiotic commonly administered to CF patients via inhalation, with DNA, which is found in high concentrations in the CF airway. We find that interactions between DNA and tobramycin are significantly modified by the presence of mixtures of amphiphilic molecules. We measure a hierarchy of self-assembled structures formed between tobramycin, DNA, and the amphiphile mixtures and show how interactions between these components can be controlled. Results indicate that mixtures of cationic and negative curvature amphiphiles optimized for DNA binding via charge matching and curvature matching can competitively displace bound tobramycin from DNA and thereby drastically suppress tobramycin-DNA binding and resultant antimicrobial inactivation. Growth inhibition assays confirm the increased activity of tobramycin in the presence of DNA with the addition of the amphiphiles. These results suggest that optimized cationic amphiphile solutions have the potential to enhance antimicrobial function in highly infected environments that contain increased concentrations of anionic inflammatory polymers.

  6. Prospects for circumventing aminoglycoside kinase mediated antibiotic resistance

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    Kun eShi

    2013-06-01

    Full Text Available Aminoglycosides are a class of antibiotics with a broad spectrum of antimicrobial activity. Unfortunately, resistance in clinical isolates is pervasive, rendering many aminoglycosides ineffective. The most widely disseminated means of resistance to this class of antibiotics is inactivation of the drug by aminoglycoside-modifying enzymes (AMEs. There are two principal strategies to overcoming the effects of AMEs. The first approach involves the design of novel aminoglycosides that can evade modification. Although this strategy has yielded a number of superior aminoglycoside variants, their efficacy cannot be sustained in the long term. The second approach entails the development of molecules that interfere with the mechanism of AMEs such that the activity of aminoglycosides is preserved. Although such a molecule has yet to enter clinical development, the search for AME inhibitors has been greatly facilitated by the wealth of structural information amassed in recent years. In particular, aminoglycoside phosphotransferases or kinases (APHs have been studied extensively and crystal structures of a number of APHs with diverse regiospecificity and substrate specificity have been elucidated. In this review, we present a comprehensive overview of the available APH structures and recent progress in APH inhibitor development, with a focus on the structure-guided strategies.

  7. DNA-Aptamers Binding Aminoglycoside Antibiotics

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    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.

  8. Aminoglycoside antibiotics and autism: a speculative hypothesis

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    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.

  9. Termite usage associated with antibiotic therapy: enhancement of aminoglycoside antibiotic activity by natural products of Nasutitermes corniger (Motschulsky 1855)

    OpenAIRE

    2009-01-01

    Abstract Background Several species from Insecta are used as remedies. Among these species, the termite Nasutitermes corniger is commonly used in traditional medicine in Northeast Brazil. The present work tests the modifying antibiotic activity of Nasutitermes corniger, a termite used in folk medicine in Northeastern region of Brazil. Methods Chlorpromazine and decocts of N. corniger were collected from two different plant species used in the traditional medicine were tested for their antimic...

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

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    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.

  11. Properties of Achromobacter xylosoxidans highly resistant to aminoglycoside antibiotics.

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    Nakamoto, Sachiko; Goda, Natsumi; Hayabuchi, Tatsuya; Tamaki, Hiroo; Ishida, Ayami; Suzuki, Ayaka; Nakano, Kaori; Yui, Shoko; Katsumata, Yuto; Yamagami, Yuki; Burioka, Naoto; Chikumi, Hiroki; Shimizu, Eiji

    2016-04-01

    We herein discovered a highly resistant clinical isolate of Pseudomonas aeruginosa with MICs to amikacin, gentamicin, and arbekacin of 128 μg/mL or higher in a drug sensitivity survey of 92 strains isolated from the specimens of Yoka hospital patients between January 2009 and October 2010, and Achromobacter xylosoxidans was separated from this P. aeruginosa isolate. The sensitivity of this bacterium to 29 antibiotics was investigated. The MICs of this A. xylosoxidans strain to 9 aminoglycoside antibiotics were: amikacin, gentamicin, arbekacin, streptomycin, kanamycin, neomycin, and spectinomycin, 1,024 μg/mL or ≥ 1,024 μg/mL; netilmicin, 512 μg/mL; and tobramycin, 256 μg/mL. This strain was also resistant to dibekacin. This aminoglycoside antibiotic resistant phenotype is very rare, and we are the first report the emergence of A. xylosoxidans with this characteristic.

  12. A teratological study of aminoglycoside antibiotic treatment during pregnancy.

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    Czeizel, A E; Rockenbauer, M; Olsen, J; Sørensen, H T

    2000-01-01

    The aim of this study was to investigate the teratogenicity of aminoglycoside antibiotics, such as parenteral gentamicin, streptomycin, tobramycin and oral neomycin, during pregnancy. Pair analysis of cases with congenital abnormalities and matched healthy controls was carried out. The setting was the population-based dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-96. In total, 38,151 pregnant women who had newborn infants without any defects (control group) and 22,865 pregnant women who had foetuses or newborns with congenital abnormalities were included in the study. 38 (0.16%) and 42 (0.11%) pregnant women in the case and control groups, respectively, were treated with the aminoglycosides studied. A teratogenic potential of gentamicin and neomycin was not indicated by a comparison of the occurrence of aminoglycoside antibiotic treatments in the total control group as referent with the figures of different congenital abnormality groups. In addition, the case-control pair analysis during the second-third months of pregnancy did not show a teratogenic risk of gentamicin and neomycin. The conclusion of this study is that treatment with parenteral gentamicin and oral neomycin during pregnancy presents no detectable teratogenic risk to the foetus, when restricted to structural developmental disturbances.

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

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    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.

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

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

    2015-01-01

    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. Phytochemical screening and synergistic interactions between aminoglycosides, selected antibiotics and extracts from the bryophyte Octoblepharum albidum Hedw (Calymperaceae

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    Vidal C.A.S.

    2012-01-01

    Full Text Available This work is the first to describe the modulation of antibiotic activity of the bryophyte Octoblepharum albidum Hedw extract. The antibacterial activity of ethanolic extract of O. albidum (EEOa, alone and in association with aminoglycosides, was determined against six bacterial strains by a microdilution test. The results showed a similar inhibitory activity of EEOa against Escherichia coli ATCC 25922 and Klebsiella pneumoniae ATCC 33018 (MICs 512 μg/mL. The synergistic effect of the extracts and aminoglycosides was also verified. The most pronounced effects were obtained with EEOa + gentamicin against E. coli and EEOa + kanamycin against K. pneumoniae with MICs reduction (128 to 32 μg/mL. The data from this study are indicative of the antibacterial activity of the bryophyte O. albidum extracts and its potential in modifying the resistance of aminoglycosides analyzed.

  16. Resistance mechanisms of kanamycin-, neomycin-, and streptomycin-producing streptomycetes to aminoglycoside antibiotics.

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    Hotta, K; Yamamoto, H; Okami, Y; Umezawa, H

    1981-09-01

    Streptomyces kanamyceticus ISP5500, S. fradiae ISP5063 and S. griseus ISP5236, which produce kanamycin, neomycin or streptomycin respectively, were highly resistant to the antibiotics they produced. Polyphenylalanine synthesis in cell free systems was also resistant to the action of the antibiotics. Reciprocal exchange between ribosomes and S150 fractions from the three strains revealed that the S150 fraction of each strain had an enzyme activity that inactivated the appropriate antibiotic whereas the ribosomes were susceptible to the antibiotics. It was concluded that the resistance of the in vitro polyphenylalanine synthesizing systems of these antibiotics was due to the presence of inactivating enzymes. Furthermore, S. fradiae and S. kanamyceticus were highly resistant to aminocyclitol-containing aminoglycoside antibiotics other than those produced by the two strains. In these cases, the inactivating enzymes were found to have a major role in the resistance mechanism. However, the resistance of S. kanamyceticus ISP5500 to streptomycin seems to be due to resistance at the ribosomal level.

  17. Environmental and genetic factors affecting mutability to aminoglycoside antibiotics among Escherichia coli K12 strains

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    Monteiro A.C.M.

    2003-01-01

    Full Text Available Environmental and genetic factors affecting the in vitro spontaneous mutation frequencies to aminoglycoside resistance in Escherichia coli K12 were investigated. Spontaneous mutation frequencies to kanamycin resistance were at least 100 fold higher on modified Luria agar (L2 plates, when compared to results obtained in experiments carried out with Nutrient agar (NA plates. In contrast to rifampincin, the increased mutability to kanamycin resistance could not be attributed to a mutator phenotype expressed by DNA repair defective strains. Kanamycin mutant selection windows and mutant preventive concentrations on L2 plates were at least fourfold higher than on NA plates, further demonstrating the role of growth medium composition on the mutability to aminoglycosides. Mutability to kanamycin resistance was increased following addition of sorbitol, suggesting that osmolarity is involved on the spontaneous mutability of E. coli K12 strains to aminoglycosides. The spontaneous mutation rates to kanamycin resistance on both L2 and NA plates were strictly associated with the selective antibiotic concentrations. Moreover, mutants selected at different antibiotic concentrations expressed heterogeneous resistance levels to kanamycin and most of them expressing multiple resistance to all tested aminoglycoside antibiotics (gentamicin, neomycin, amykacin and tobramycin. These results will contribute to a better understanding of the complex nature of aminoglycoside resistance and the emergence of spontaneous resistant mutants among E. coli K12 strains.

  18. Role of aromatic rings in the molecular recognition of aminoglycoside antibiotics: implications for drug design.

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    Vacas, Tatiana; Corzana, Francisco; Jiménez-Osés, Gonzalo; González, Carlos; Gómez, Ana M; Bastida, Agatha; Revuelta, Julia; Asensio, Juan Luis

    2010-09-01

    Aminoglycoside antibiotics participate in a large variety of binding processes involving both RNA and proteins. The description, in recent years, of several clinically relevant aminoglycoside/receptor complexes has greatly stimulated the structural-based design of new bioactive derivatives. Unfortunately, design efforts have frequently met with limited success, reflecting our incomplete understanding of the molecular determinants for the antibiotic recognition. Intriguingly, aromatic rings of the protein/RNA receptors seem to be key actors in this process. Indeed, close inspection of the structural information available reveals that they are frequently involved in CH/pi stacking interactions with sugar/aminocyclitol rings of the antibiotic. While the interaction between neutral carbohydrates and aromatic rings has been studied in detail during past decade, little is known about these contacts when they involve densely charged glycosides. Herein we report a detailed experimental and theoretical analysis of the role played by CH/pi stacking interactions in the molecular recognition of aminoglycosides. Our study aims to determine the influence that the antibiotic polycationic character has on the stability, preferred geometry, and dynamics of these particular contacts. With this purpose, different aminoglycoside/aromatic complexes have been selected as model systems. They varied from simple bimolecular interactions to the more stable intramolecular CH/pi contacts present in designed derivatives. The obtained results highlight the key role played by electrostatic forces and the desolvation of charged groups in the molecular recognition of polycationic glycosides and have clear implications for the design of improved antibiotics.

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

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    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

  20. Complexation of anionic copolymers of acrylamide and N-(2-hydroxypropyl)methacrylamide with aminoglycoside antibiotics

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    Solovskii, M. V.; Tarabukina, E. B.; Amirova, A. I.; Zakharova, N. V.; Smirnova, M. Yu.; Gavrilova, I. I.

    2014-03-01

    The complexation of aminoglycoside antibiotics neomycin, gentamicin, kanamycin, and amikacin in the form of free bases with carboxyl- and sulfo-containing copolymers of acrylamide and N-(2-hydroxypropyl)methacrylamide (HPMA) in water and water-salt solutions is studied by means of viscometry, equilibrium dialysis, potentiometric titration, and molecular hydrodynamics. Factors influencing the stability of formed copolymer-antibiotic complexes and determinations of their toxicity are established.

  1. [Zebrafish model for the study on drug ototoxicity of aminoglycoside antibiotics].

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    Zhao, Zhuang; Tong, Jun-Wei; Zhang, Jing-Pu; You, Xue-Fu; Jiang, Jian-Dong; Hu, Chang-Qin

    2011-08-01

    Aminoglycoside antibiotics, due to their strong antibacterial effects and broad antimicrobial spectra, have been very commonly used in clinical practice in the past half century. However, aminoglycoside antibiotics manifest severe ototoxicity and nephrotoxicity, and are one of top factors in hearing loss. In this study, three members of the aminoglycoside antibiotics family, gentamycin, neomycin and streptomycin, were chosen as the representatives to be investigated for their toxicity to the embryonic development and the larva hair cells in zebrafish, and also to their target genes associated with hearing-related genes. The results showed that: (1) the lethal effect of all three drugs demonstrated a significant dependence on concentration, and the severity order of the lethal effect was streptomycin > neomycin > gentamycin; (2) all the three drugs caused the larva trunk bending in resting state at 5 dpf (day past fertilization), probably due to their ototoxicity in the physical imbalance and postural abnormalities; (3) impairment and reducing of the hair cells were observed in all three cases of drug treatment; (4) four genes, eya1, val, otx2 and dlx6a, which play an important role in the development of hearing organs, showed differential and significant decrease of gene expression in a drug concentration-dependent manner. This study for the first time reports the relevance between the expression of hearing genes and the three ototoxic antibiotics and also proved the feasibility of establishing a simple, accurate, intuitive and fast model with zebrafish for the detection of drug ototoxicity.

  2. Crystal structures of antibiotic-bound complexes of aminoglycoside 2''-phosphotransferase IVa highlight the diversity in substrate binding modes among aminoglycoside kinases.

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    Shi, Kun; Houston, Douglas R; Berghuis, Albert M

    2011-07-19

    Aminoglycoside 2''-phosphotransferase IVa [APH(2'')-IVa] is a member of a family of bacterial enzymes responsible for medically relevant resistance to antibiotics. APH(2'')-IVa confers high-level resistance against several clinically used aminoglycoside antibiotics in various pathogenic Enterococcus species by phosphorylating the drug, thereby preventing it from binding to its ribosomal target and producing a bactericidal effect. We describe here three crystal structures of APH(2'')-IVa, one in its apo form and two in complex with a bound antibiotic, tobramycin and kanamycin A. The apo structure was refined to a resolution of 2.05 Å, and the APH(2'')-IVa structures with tobramycin and kanamycin A bound were refined to resolutions of 1.80 and 2.15 Å, respectively. Comparison among the structures provides insight concerning the substrate selectivity of this enzyme. In particular, conformational changes upon substrate binding, involving rotational shifts of two distinct segments of the enzyme, are observed. These substrate-induced shifts may also rationalize the altered substrate preference of APH(2'')-IVa in comparison to those of other members of the APH(2'') subfamily, which are structurally closely related. Finally, analysis of the interactions between the enzyme and aminoglycoside reveals a distinct binding mode as compared to the intended ribosomal target. The differences in the pattern of interactions can be utilized as a structural basis for the development of improved aminoglycosides that are not susceptible to these resistance factors.

  3. Investigation on the Mechanism of Exacerbation of Myasthenia Gravis by Aminoglycoside Antibiotics in Mouse Model

    Institute of Scientific and Technical Information of China (English)

    LIU Changqin; HU Fang

    2005-01-01

    Summary: To investigate the underlying mechanism of the exacerbation of myasthenia gravis by aminoglycoside antibiotics. C57/BL6 mice were immunized with acetylcholine receptor (AChR), extracted from electric organ of Narcine timilei according to Xu Haopeng's methods, in complete Fruend's adjuvant (CFA) to establish experimental autoimmune myasthenia gravis (EAMG). EAMG mice were divided randomly into 5 groups: MG group, NS group and three antibiotics groups. The clinical symptom scores of mice were evaluated on d7 after the last immunization and d14 of antibiotics treatment. Repetitive nerve stimulation (RNS) was performed and the levels of anti-AChR antibody (AChR-Ab) were tested at the same time. The mean clinical symptom grades of gentamycin group (1.312, 2.067), amikacin group (1.111, 1.889) and etimicin group (1.263, 1.632) were significantly higher than those of MG group (1.000, 1.200) (P<0.05). The positive rates of RNS of three antibiotics groups were 69.23 %, 58.82 % and 63.16 % respectively, which were significantly higher than those of MG group and NS group (40.00 %, 40.00 %, P<0.05). The AChR-Ab level in serum and the expression of AChR on neuromuscular junction (NMJ) of mice in three antibiotics groups were also higher than those of MG group. Our results indicated that aminoglycoside antibiotics could aggravate the symptom of myasthenia gravis. The exacerbation of myasthenia gravis by these antibiotics probably involves competitively restraining the release of acetylcholine from presynaptic membrane, impairing the depolarization of postsynaptic membrane, depressing the irritability of myocyte membrane around the end-plate membrane and consequently leading to the blockade of neuromuscular junction.

  4. Impairment of membrane phosphoinositide metabolism by aminoglycoside antibiotics: streptomycin, amikacin, kanamycin, dibekacin, gentamicin and neomycin.

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    Marche, P; Koutouzov, S; Girard, A

    1983-11-01

    Like many amphiphilic cationic drugs, aminoglycosides are able to produce phospholipidosis, mainly by inhibiting enzymes involved in phospholipid metabolism. Phosphoinositides have been suggested to function as receptors for aminoglycosides. Therefore, we investigated the influence of these drugs upon phosphoinositide metabolism by measuring the 32P-incorporation into the polyphosphoinositides, using the rat erythrocyte membrane as a model. Depending upon the experimental conditions, neomycin induced a decrease and/or an increase in the 32P-labeling of triphosphoinositides (TPI) and of diphosphoinositides (DPI), respectively. These variations were rapid and depended upon the drug concentration. At 0.3 mM, neomycin reversed the distribution of radioactivities associated with DPI and TPI without modifying the total radioactivity incorporated. This drug concentration altered neither the Mg++-activated TPI-specific phosphomonoesterase activity nor the Ca++-activated polyphosphoinositide phosphodiesterase activity. It appears likely that the drug inhibits the DPI-kinase activity, by interacting with DPI and thereby lowering the substrate availability. Over the range of concentrations studied (up to 1-2 mM), gentamicin, kanamycin and dibekacin behave as neomycin. However, their effects could be observed only at drug concentrations higher than those of neomycin. By contrast, streptomycin and amikacin did not alter the 32P-labeling of TPI and of DPI. The order of potency of aminoglycosides for the impairment of the phosphoinositide interconversion was neomycin, gentamicin, dibekacin, kanamycin. A possible relationship between the toxicity of aminoglycosides and their capacity to impair the phosphoinositide metabolism is discussed.

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

    Science.gov (United States)

    Cunningham-Oakes, Edward; Soren, Odel; Moussa, Caroline; Rathor, Getika; Liu, Yingjun; Coates, Anthony; Hu, Yanmin

    2015-01-01

    Infections caused by methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. 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.

  6. 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.

  7. Solvent reorganization plays a temperature-dependent role in antibiotic selection by a thermostable aminoglycoside nucleotidyltransferase-4'.

    Science.gov (United States)

    Jing, Xiaomin; Serpersu, Engin H

    2014-09-02

    The aminoglycoside nucleotidyltransferase-4' (ANT) is an enzyme that causes resistance to a large number of aminoglycoside antibiotics by nucleotidylation of the 4'-site on these antibiotics. The effect of solvent reorganization on enzyme-ligand interactions was investigated using a thermophilic variant of the enzyme resulting from a single-site mutation (T130K). Data showed that the binding of aminoglycosides to ANT causes exposure of polar groups to solvent. However, solvent reorganization becomes the major contributor to the enthalpy of the formation of enzyme-aminoglycoside complexes only above 20 °C. The change in heat capacity (ΔCp) shows an aminoglycoside-dependent pattern such that it correlates with the affinity of the ligand for the enzyme. Differences in ΔCp values determined in H2O and D2O also correlated with the ligand affinity. The temperature-dependent increase in the offset temperature (Toff), the temperature difference required to observe equal enthalpies in both solvents, is also dependent on the binding affinity of the ligand, and the steepest increase was observed with the tightest binding aminoglycoside, neomycin. Overall, these data, together with earlier observations with a different enzyme, the aminoglycoside N3-acetyltransferase-IIIb [Norris, A. L., and Serpersu, E. H. (2011) Biochemistry 50, 9309], show that solvent reorganization or changes in soft vibrational modes of the protein are interchangeable with respect to the role of being the major contributor to complex formation depending on temperature. These data suggest that such effects may more generally apply to enzyme-ligand interactions, and studies at a single temperature may provide only a part of the whole picture of thermodynamics of enzyme-ligand interactions.

  8. Effects of the aminoglycoside antibiotics, streptomycin and neomycin, on neuromuscular transmission. II. Postsynaptic considerations.

    Science.gov (United States)

    Fiekers, J F

    1983-06-01

    The postsynaptic effects of two aminoglycoside antibiotics, streptomycin and neomycin, were studied on miniature end-plate currents (mepcs) and acetylcholine-induced end-plate current fluctuations in voltage-clamped costocutaneous muscles of the garter snake (species Thamnophis). Neomycin decreased the amplitude of mepcs and accelerated the time constants of mepc decay in a concentration-dependent manner without altering the single exponential nature of mepc decay. Neomycin also produced a voltage- and concentration-dependent nonlinearity in the current/voltage relationship. The relationship between the time constants of mepc decay and membrane potential was progressively reduced with increasing concentrations of neomycin. A concentration-dependent reduction in single channel conductance and channel lifetime was also obtained with neomycin. In contrast, streptomycin, in concentrations up to 5 X 10(-5) M, did not significantly alter either mepc amplitude, the time constant of mepc decay, the relationship between the mepc decay time constant and membrane potential or the lifetime and conductance of single end-plate channels. In very high concentrations (greater than 1 mM) streptomycin decreased mepc amplitude and prolonged mepc decay at hyperpolarized membrane potentials. The results suggest that neomycin interacts with the ionic channels of the acetylcholine receptor in their open configuration, whereas streptomycin acts primarily by blocking the receptor. The significant differences in the molecular actions of these two antibiotics may provide an explanation for the observed differences in the character and reversal of the neuromuscular block produced by these antibiotics.

  9. 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.

  10. 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

  11. Combinations of β-lactam or aminoglycoside antibiotics with plectasin are synergistic against methicillin-sensitive and methicillin-resistant Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Yanmin Hu

    Full Text Available 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

  12. Synergistic interaction of PMAP-36 and PRW4 with aminoglycoside antibiotics and their antibacterial mechanism.

    Science.gov (United States)

    Wang, Zeyun; Zhang, Licong; Wang, Jue; Wei, Dandan; Shi, Baoming; Shan, Anshan

    2014-12-01

    The antimicrobial peptide PMAP-36 is a highly cationic and amphipathic α-helical peptide. PRW4 is a truncated analog that replaces paired lysine residues with tryptophan along the N-terminal and deletes the C-terminal hydrophobic tail of PMAP-36. Studies on the two peptides have already been performed. However, whether there is a synergistic effect with antibiotics has not been investigated, and the study of the antibacterial mechanism of the peptides is inadequate. In this study, antibiotic-peptide combinations were tested against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, and the confocal laser scanning microscopy (LSCM) and DNA gel retardation were measured. The results indicated synergy between the peptides and gentamicin when tested against E. coli [fractional lethal concentration (FLC) peptides and gentamicin against S. aureus (0.5 peptides against E. coli and S. aureus (1 DNA binding suggest that PMAP-36 was able to translocate across the bacterial membranes and interact with intracellular DNA, but PRW4 presented no DNA-binding ability. These results indicate that the combination of PMAP-36 and PRW4 with aminoglycosides may provide useful information for clinical application, and the antibacterial mechanism of peptides likely does not solely involve cytoplasmic-membrane permeabilization.

  13. Ribosomes of the extremely thermophilic eubacterium Thermotoga maritima are uniquely insensitive to the miscoding-inducing action of aminoglycoside antibiotics.

    OpenAIRE

    1988-01-01

    Poly(U)- and poly(UG)-programmed cell-free systems were developed from the extreme thermophilic, anaerobic eubacterium Thermotoga maritima, and their susceptibility to aminoglycoside and other antibiotics was assayed at a temperature (75 degrees C) close to the physiological optimum (80 degrees C) for cell growth and in vitro polypeptide synthesis, using a Bacillus stearothermophilus system as the reference. The synthetic capacity of the Thermotoga assay mixture was abolished by the eubacteri...

  14. Mutations in eukaryotic 18S ribosomal RNA affect translational fidelity and resistance to aminoglycoside antibiotics.

    Science.gov (United States)

    Chernoff, Y O; Vincent, A; Liebman, S W

    1994-02-15

    Mutations have been created in the Saccharomyces cerevisiae 18S rRNA gene that correspond to those known to be involved in the control of translational fidelity or antibiotic resistance in prokaryotes. Yeast strains, in which essentially all chromosomal rDNA repeats are deleted and all cellular rRNAs are encoded by plasmid, have been constructed that contain only mutant 18S rRNA. In Escherichia coli, a C-->U substitution at position 912 of the small subunit rRNA causes streptomycin resistance. Eukaryotes normally carry U at the corresponding position and are naturally resistant to streptomycin. We show that a U-->C transition (rdn-4) at this position of the yeast 18S rRNA gene decreases resistance to streptomycin. The rdn-4 mutation also increases resistance to paromomycin and G-418, and inhibits nonsense suppression induced by paromomycin. The same phenotypes, as well as a slow growth phenotype, are also associated with rdn-2, whose prokaryotic counterpart, 517 G-->A, manifests itself as a suppressor rather than an antisuppressor. Neither rdn-2- nor rdn-4-related phenotypes could be detected in the presence of the normal level of wild-type rDNA repeats. Our data demonstrate that eukaryotic rRNA is involved in the control of translational fidelity, and indicate that rRNA features important for interactions with aminoglycosides have been conserved throughout evolution.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    Paul Skorup

    Full Text Available 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 (p<0.001. Growth of bacteria in the spleen was reduced in the two antibiotic groups compared with the controls (p<0.01; no difference was noted between the two antibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (p<0.05. High blood bactericidal capacity at baseline was associated with decreased growth in the blood and spleen (p<0.05. The addition of tobramycin to cefuroxime results in increased antibiotic-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.

  17. Antinociceptive potency of aminoglycoside antibiotics and magnesium chloride: a comparative study on models of phasic and incisional pain in rats

    Directory of Open Access Journals (Sweden)

    W.A. Prado

    2002-03-01

    Full Text Available A close relationship exists between calcium concentration in the central nervous system and nociceptive processing. Aminoglycoside antibiotics and magnesium interact with N- and P/Q-type voltage-operated calcium channels. In the present study we compare the antinociceptive potency of intrathecal administration of aminoglycoside antibiotics and magnesium chloride in the tail-flick test and on incisional pain in rats, taken as models of phasic and persistent post-surgical pain, respectively. The order of potency in the tail-flick test was gentamicin (ED50 = 3.34 µg; confidence limits 2.65 and 4.2 > streptomycin (5.68 µg; 3.76 and 8.57 = neomycin (9.22 µg; 6.98 and 12.17 > magnesium (19.49 µg; 11.46 and 33.13. The order of potency to reduce incisional pain was gentamicin (ED50 = 2.06 µg; confidence limits 1.46 and 2.9 > streptomycin (47.86 µg; 26.3 and 87.1 = neomycin (83.17 µg; 51.6 and 133.9. The dose-response curves for each test did not deviate significantly from parallelism. We conclude that neomycin and streptomycin are more potent against phasic pain than against persistent pain, whereas gentamicin is equipotent against both types of pain. Magnesium was less potent than the antibiotics and effective in the tail-flick test only.

  18. Antinociceptive potency of aminoglycoside antibiotics and magnesium chloride: a comparative study on models of phasic and incisional pain in rats.

    Science.gov (United States)

    Prado, W A; Machado Filho, E B

    2002-03-01

    A close relationship exists between calcium concentration in the central nervous system and nociceptive processing. Aminoglycoside antibiotics and magnesium interact with N- and P/Q-type voltage-operated calcium channels. In the present study we compare the antinociceptive potency of intrathecal administration of aminoglycoside antibiotics and magnesium chloride in the tail-flick test and on incisional pain in rats, taken as models of phasic and persistent post-surgical pain, respectively. The order of potency in the tail-flick test was gentamicin (ED50 = 3.34 microg; confidence limits 2.65 and 4.2) > streptomycin (5.68 microg; 3.76 and 8.57) = neomycin (9.22 microg; 6.98 and 12.17) > magnesium (19.49 microg; 11.46 and 33.13). The order of potency to reduce incisional pain was gentamicin (ED50 = 2.06 microg; confidence limits 1.46 and 2.9) > streptomycin (47.86 microg; 26.3 and 87.1) = neomycin (83.17 microg; 51.6 and 133.9). The dose-response curves for each test did not deviate significantly from parallelism. We conclude that neomycin and streptomycin are more potent against phasic pain than against persistent pain, whereas gentamicin is equipotent against both types of pain. Magnesium was less potent than the antibiotics and effective in the tail-flick test only.

  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. 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.

  1. Crystallographic Studies of Two Bacterial AntibioticResistance Enzymes: Aminoglycoside Phosphotransferase (2')-Ic and GES-1\\beta-lactamase

    Energy Technology Data Exchange (ETDEWEB)

    Brynes, Laura; /Rensselaer Poly.

    2007-10-31

    Guiana Extended-Spectrum-1 (GES-1) and Aminoglycoside phosphotransferase (2')-Ic (APH(2')-Ic) are two bacteria-produced enzymes that essentially perform the same task: they provide resistance to an array of antibiotics. Both enzymes are part of a growing resistance problem in the medical world. In order to overcome the ever-growing arsenal of antibiotic-resistance enzymes, it is necessary to understand the molecular basis of their action. Accurate structures of these proteins have become an invaluable tool to do this. Using protein crystallography techniques and X-ray diffraction, the protein structure of GES-1 bound to imipenem (an inhibitor) has been solved. Also, APH(2')-Ic has been successfully crystallized, but its structure was unable to be solved using molecular replacement using APH(2')-Ib as a search model. The structure of GES-1, with bound imipenem was solved to a resolution of 1.89A, and though the inhibitor is bound with only moderate occupancy, the structure shows crucial interactions inside the active site that render the enzyme unable to complete the hydrolysis of the {beta}-lactam ring. The APH(2')-Ic dataset could not be matched to the model, APH(2')-Ib, with which it shares 25% sequence identity. The structural information gained from GES-1, and future studies using isomorphous replacement to solve the APH(2')-Ic structure can aid directly to the creation of novel drugs to combat both of these classes of resistance enzymes.

  2. Special characteristics of fluorescence and resonance Rayleigh scattering for cadmium telluride nanocrystal aqueous solution and its interactions with aminoglycoside antibiotics

    Institute of Scientific and Technical Information of China (English)

    LI TaiShan; LIU ShaoPu; LIU ZhongFang; HU XiaoLi; ZHANG LiPing

    2009-01-01

    CdTe nanocrystals (CdTe NCs) were achieved by reaction of CdCl2 with KHTe solution and were capped with sodium mercaptoacetate. The product was detected by transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), energy dispersive spectroscopy (EDS), fluorescence spectra, ultraviolet-visible spectra and X-ray diffraction (XRD). The CdTe NCs are of cubic structure and the average size is about 5 nm. The fluorescence quantum yield of CdTe NCs aqueous solution increased from 37% to 97% after 20 d under room light. The maximum λem of fluorescence changed from 543 nm to 510 nm and the blue shift was 33 nm. CdTe NCs aqueous solution can be steady for at least 10 months at 4℃ in a refrigerator. The resonance Rayleigh scattering (RRS) of CdTe NCs in the aqueous solution was investigated. The maximum scattering peak was located at about 554 nm. The interactions of CdTe NCs with amikacin sulfate (AS) and micronomicin sulfate (MS) were in-vestigated respectively. The effects of AS and MS on fluorescence and RRS of CdTe NCs were analyzed. It was found that AS and MS quenched the photoluminescence of CdTe NCs and enhanced RRS of CdTe NCs. Under optimum conditions, there are linear relationships between quenching intensity (F0-F), intensity of RRS (1-10) and concentration of AS and MS. The detection limits (3σ) of AS and MS are re-spectively 3.4 ng.mL-1 and 2.6 ng.mL-1 by the fluorescence quenching method, and 15.2 ng.mL-1 and 14.0 ng.mL-1 by the RRS method. The methods have high sensitivity, thus CdTe NCs may be used as fluorescence probes and RRS probes for the detection of aminoglycoside antibiotics.

  3. [PK/PD modeling of aminoglycoside nephrotoxicity].

    Science.gov (United States)

    Rougier, F; Corvaisier, S; Ducher, M; Claude, D; Jelliffe, R W; Maire, P

    2003-06-01

    Aminoglycosides are bactericidial antibiotics with a serum concentration-dependent activity. They are mainly eliminated by the kidneys and the main difficulty arising in clinical use is their uptake by the renal cortex which leads to nephrotoxicity. An ototoxicity is also reported. We propose a PK/PD modelling of aminoglycoside nephrotoxicity which unifies more fourty years of physiological knowledge. This deterministic model successively describes the pharmacokinetics of aminoglycosides, their storage into renal cortex, their effect on renal cells, their consequences on the renal function through tubuloglomerular feedback and the changes in the serum concentrations of creatinine that is considered as a toxicity marker. The simulation of the model displays the leading effect of the shape and daily-time of administration schedule on the search for minimizing toxicity.

  4. Mechanistic studies of copper(II)-aminoglycoside mediated DNA damage and magnesium catalyzed nuclease activity of hammerhead ribozyme

    Science.gov (United States)

    Patwardhan, Anjali A.

    The antibacterial activity of aminoglycosides stems from their high affinity binding to the 16S rRNA in bacteria resulting in inhibition of protein synthesis. Used to treat acute bacterial infections these antibiotics have limited applications due to their high dosage requirements and the emergence of resistant strains. We have synthesized and characterized Cu(II) derivatives of the aminoglycosides, kanamycin A, tobramycin, neamine, kanamycin B, neomycin B, and paromomycin. The first three exhibit preferential and tight binding to Cu(II) as against neomycin B and kanamycin B and paromomycin. EPR of frozen solutions and UV-visible spectroscopy suggest a change in geometry around the Cu(II) but the stabilities of the complexes in water differ. These copper derivatives efficiently cleave plasmid DNA at micromolar concentrations (hydrolytic) and at nanomolar concentrations in the presence co-reactants like hydrogen peroxide or ascorbic acid. Hydrolysis is multi turnover and exhibits Michelis-Menten kinetics with enzyme-like behavior whereas oxidative cleavage is highly specific with C-4' H abstraction resulting in characteristic base propenal and nucleotide base products. Hydroxyl radicals generated are copper based and are generated in close proximity of the substrate. Hammerhead ribozymes are selectively hydrolyzed in the presence of divalent ions with Mg2+ being the metal ion of choice in vivo . Our studies with complex ions like cobalt hexaammine and fac-triamminetriaquochromium(III) establish outer sphere interactions of Mg2+ with the hammerhead in the catalytic site. There are two sets of sites, one structural and one catalytic. Complex ions in the catalytic site and divalent ions in the structural site result in a slow but active hammerhead ribozyme suggesting that the complex ions are not inhibitory, contrary to what was suggested previously.

  5. Special characteristics of fluorescence and resonance Rayleigh scattering for cadmium telluride nanocrystal aqueous solution and its interactions with aminoglycoside antibiotics

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    CdTe nanocrystals(CdTe NCs) were achieved by reaction of CdCl2 with KHTe solution and were capped with sodium mercaptoacetate.The product was detected by transmission electron microscopy(TEM),high-resolution transmission electron microscopy(HRTEM),energy dispersive spectroscopy(EDS),fluorescence spectra,ultraviolet-visible spectra and X-ray diffraction(XRD).The CdTe NCs are of cubic structure and the average size is about 5 nm.The fluorescence quantum yield of CdTe NCs aqueous solution increased from 37% to 97% after 20 d under room light.The maximum λem of fluorescence changed from 543 nm to 510 nm and the blue shift was 33 nm.CdTe NCs aqueous solution can be steady for at least 10 months at 4℃ in a refrigerator.The resonance Rayleigh scattering(RRS) of CdTe NCs in the aqueous solution was investigated.The maximum scattering peak was located at about 554 nm.The interactions of CdTe NCs with amikacin sulfate(AS) and micronomicin sulfate(MS) were investigated respectively.The effects of AS and MS on fluorescence and RRS of CdTe NCs were analyzed.It was found that AS and MS quenched the photoluminescence of CdTe NCs and enhanced RRS of CdTe NCs.Under optimum conditions,there are linear relationships between quenching intensity(F0-F),intensity of RRS(I-I0) and concentration of AS and MS.The detection limits(3б) of AS and MS are respectively 3.4 ng·mL-1 and 2.6 ng·mL-1 by the fluorescence quenching method,and 15.2 ng·mL-1 and 14.0 ng·mL-1 by the RRS method.The methods have high sensitivity,thus CdTe NCs may be used as fluorescence probes and RRS probes for the detection of aminoglycoside antibiotics.

  6. Aminoglycoside antibiotics for NIH category II chronic bacterial prostatitis: A single-cohort study with one-year follow-up.

    Science.gov (United States)

    Magri, Vittorio; Montanari, Emanuele; Marras, Emanuela; Perletti, Gianpaolo

    2016-10-01

    Although fluoroquinolones are first-line agents for the treatment of National Institutes of Health (NIH) category II chronic bacterial prostatitis (CBP), therapy with these agents is not always feasible due to the increasing worldwide resistance of causative uropathogens. New therapeutic options are urgently required, as drugs such as β-lactam antibiotics distribute poorly to prostatic sites of infection and trimethoprim therapy is often unfeasible due to high resistance rates. The present study aimed to analyze the efficacy of aminoglycosides, administered to a cohort of 78 patients affected by fluoroquinolone-resistant CBP, or excluded from fluoroquinolone therapy due to various contraindications. Patients received netilmicin (4.5 mg/kg, once-daily, intramuscular), combined or not with a β-lactam antibiotic, for 4 weeks. Follow-up visits were scheduled 6 and 12 months after the end of treatment. Fifty-five out of 70 patients (78.6%) showed eradication of the causative pathogen, and a significant reduction of the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) total score from a baseline median value of 21 to 14 at the end of therapy, and to 9 and 8 at 6-month and 12-month follow-up assessments, respectively. The pain, voiding and quality of life subdomains of the NIH-CPSI decreased accordingly. In 15 patients showing persistence of infection, NIH-CPSI total and subdomain scores did not decrease at the end of therapy. Additional clinical parameters, such as the urinary peak flow rate, percentage voided bladder, serum prostate-specific antigen concentration, International Prostate Symptom Score and prostate volume improved significantly only in the group of patients in which the infection was eradicated. Therapy was well tolerated, and genetic testing for deafness-predisposing mitochondrial mutations allowed safer administration of aminoglycosides. These results suggest that aminoglycosides may become a therapeutic alternative for the treatment of CBP. These

  7. Validation of a quantitative and confirmatory method for residue analysis of aminoglycoside antibiotics in poultry, bovine, equine and swine kidney through liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Almeida, M P; Rezende, C P; Souza, L F; Brito, R B

    2012-01-01

    The use of aminoglycoside antibiotics in food animals is approved in Brazil. Accordingly, Brazilian food safety legislation sets maximum levels for these drugs in tissues from these animals in an effort to guarantee that food safety is not compromised. Aiming to monitor the levels of these drugs in tissues from food animals, the validation of a quantitative, confirmatory method for the detection of residues of 10 aminoglycosides antibiotics in poultry, swine, equine and bovine kidney, with extraction using a solid phase and detection and quantification by LC-MS/MS was performed. The procedure is an adaptation of the US Department of Agriculture, Food Safety and Inspection Service (USDA-FSIS) qualitative method, with the inclusion of additional clean-up and quantification at lower levels, which proved more efficient. Extraction was performed using a phosphate buffer containing trifluoroacetic acid followed by neutralization, purification on a cationic exchange SPE cartridge, with elution with methanol/acetic acid, evaporation, and dilution in ion-pair solvent. The method was validated according to the criteria and requirements of the European Commission Decision 2002/657/EC, showing selectivity with no matrix interference. Linearity was established for all analytes using the method of weighted minimum squares. CCα and CCβ varied between 1036 and 12,293 µg kg(-1), and between 1073 and 14,588 µg kg(-1), respectively. The limits of quantification varied between 27 and 688 µg kg(-1). The values of recovery for all analytes in poultry kidney, fortified in the range of 500-1500 µg kg(-1), were higher than 90%, and the relative standard deviations were lower than 15%, except spectinomycin (21.8%). Uncertainty was estimated using a simplified methodology of 'bottom-up' and 'top-down' strategies. The results showed that this method is effective for the quantification and confirmation of aminoglycoside residues and could be used by the Brazilian programme of residue

  8. Aminoglycoside antibiotics for NIH category II chronic bacterial prostatitis: A single-cohort study with one-year follow-up

    Science.gov (United States)

    Magri, Vittorio; Montanari, Emanuele; Marras, Emanuela; Perletti, Gianpaolo

    2016-01-01

    Although fluoroquinolones are first-line agents for the treatment of National Institutes of Health (NIH) category II chronic bacterial prostatitis (CBP), therapy with these agents is not always feasible due to the increasing worldwide resistance of causative uropathogens. New therapeutic options are urgently required, as drugs such as β-lactam antibiotics distribute poorly to prostatic sites of infection and trimethoprim therapy is often unfeasible due to high resistance rates. The present study aimed to analyze the efficacy of aminoglycosides, administered to a cohort of 78 patients affected by fluoroquinolone-resistant CBP, or excluded from fluoroquinolone therapy due to various contraindications. Patients received netilmicin (4.5 mg/kg, once-daily, intramuscular), combined or not with a β-lactam antibiotic, for 4 weeks. Follow-up visits were scheduled 6 and 12 months after the end of treatment. Fifty-five out of 70 patients (78.6%) showed eradication of the causative pathogen, and a significant reduction of the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI) total score from a baseline median value of 21 to 14 at the end of therapy, and to 9 and 8 at 6-month and 12-month follow-up assessments, respectively. The pain, voiding and quality of life subdomains of the NIH-CPSI decreased accordingly. In 15 patients showing persistence of infection, NIH-CPSI total and subdomain scores did not decrease at the end of therapy. Additional clinical parameters, such as the urinary peak flow rate, percentage voided bladder, serum prostate-specific antigen concentration, International Prostate Symptom Score and prostate volume improved significantly only in the group of patients in which the infection was eradicated. Therapy was well tolerated, and genetic testing for deafness-predisposing mitochondrial mutations allowed safer administration of aminoglycosides. These results suggest that aminoglycosides may become a therapeutic alternative for the treatment of CBP. These

  9. 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.

  10. 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 ...

  11. Defining RNA motif-aminoglycoside interactions via two-dimensional combinatorial screening and structure-activity relationships through sequencing.

    Science.gov (United States)

    Velagapudi, Sai Pradeep; Disney, Matthew D

    2013-10-15

    RNA is an extremely important target for the development of chemical probes of function or small molecule therapeutics. Aminoglycosides are the most well studied class of small molecules to target RNA. However, the RNA motifs outside of the bacterial rRNA A-site that are likely to be bound by these compounds in biological systems is largely unknown. If such information were known, it could allow for aminoglycosides to be exploited to target other RNAs and, in addition, could provide invaluable insights into potential bystander targets of these clinically used drugs. We utilized two-dimensional combinatorial screening (2DCS), a library-versus-library screening approach, to select the motifs displayed in a 3×3 nucleotide internal loop library and in a 6-nucleotide hairpin library that bind with high affinity and selectivity to six aminoglycoside derivatives. The selected RNA motifs were then analyzed using structure-activity relationships through sequencing (StARTS), a statistical approach that defines the privileged RNA motif space that binds a small molecule. StARTS allowed for the facile annotation of the selected RNA motif-aminoglycoside interactions in terms of affinity and selectivity. The interactions selected by 2DCS generally have nanomolar affinities, which is higher affinity than the binding of aminoglycosides to a mimic of their therapeutic target, the bacterial rRNA A-site.

  12. 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.

  13. 氨基糖苷类修饰酶引起的细菌耐药性机制的研究进展%Deciphering Mechanisms of Aminoglycoside Antibiotics with Enzymes That Cause Resistance to Their Action

    Institute of Scientific and Technical Information of China (English)

    武灵芝; 胡栋; 秦猛

    2013-01-01

    氨基糖苷类抗生素是高效、广谱的杀菌药物.随着在临床的广泛应用,抗生素的抗药性日趋严重,这在很大程度上降低了其临床应用的潜力.其中,最主要的原因就是细菌产生了一系列修饰酶修饰抗生素的特定基团,使其失去药效.细菌产生的修饰酶种类众多,主要包括磷酸化、乙酰化和腺苷化修饰酶.研究发现,一种酶可以修饰多种抗生素,同时,一种抗生素也可以被多种修饰酶修饰.由于修饰酶底物的广谱性,使得细菌的耐药性难以克服.因此,本文就氨基糖苷类修饰酶和抗生素相互作用的热力学和动力学性质进行了详细的论述,试图找出不同修饰酶失活抗生素药物的共同作用机制.这将为设计新的抗生素药物及修饰酶抑制剂、克服细菌的耐药性,提供理论指导和技术支持.%Aminoglycosides are valuable and broad spectrum of bactericidal antibiotics. However, their therapeutic effectiveness has been severely reduced in recent decades due to the emergence of bacterial strains that are insensitive to aminoglycoside action. The most common mode of bacterial resistance to aminoglycoside antibiotics is the enzyme-catalysed chemical modification on the special groups of the drug. Aminoglycoside-modifying enzymes are widely distributed among bacterial pathogens and include O-phosphoryltransferases (kinases), N-acetyltransferases, and O-adenyltransferases. These enzymes can use several aminoglycosides as substrates regardless of size and structural differences among them. Conversely, each aminoglycoside can be a substrate for many different AGMEs. In this review, the authors describe the thermodynamic characterization of aminoglycoside modified enzyme interacted with antibiotics in an effort to define shared aspects of enzyme-aminoglycoside complexes, which provides the necessary tools and understanding to design new drugs to combat antibiotic resistance.

  14. 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

    Decoding of genetic information occurs upon interaction of an mRNA codon-tRNA anticodon complex with the small subunit of the ribosome. The ribosomal decoding region is associated with highly conserved sequences near the 3' end of 16 S rRNA. The decoding process is perturbed by the aminoglycoside...... of universally conserved nucleotides at 1406 to 1408 and 1494 to 1495 in the decoding region of plasmid-encoded bacterial 16 S rRNA. Phenotypic changes range from the benign effect of U1406-->A or A1408-->G substitutions, to the highly deleterious 1406G and 1495 mutations that assemble into 30 S subunits...... but are defective in forming functional ribosomes. Changes in the local conformation of the decoding region caused by these mutations were identified by chemical probing of isolated 30 S subunits. Ribosomes containing 16 S rRNA with mutations at positions 1408, 1407+1494, or 1495 had reduced affinity...

  15. Evaluation of Antibacterial Activity of Aminoglycosides and Modulating the Essential Oil of Cymbopogon citratus (DC. Stapf

    Directory of Open Access Journals (Sweden)

    Saulo R. TINTINO

    2014-05-01

    Full Text Available  Several works demonstrated the importance of the study of natural products as an alternative source for new antimicrobial drugs or for modulators for these ones. In this point, the aim of this was to investigate the antibacterial activity and the possible interactions between the essential oil of Cymbopogon citratus alone and in association with aminoglycosides against standard and clinically isolated strains of multidrug-resistant bacteria such as S. aureus, E. coli and P. aeruginosa by microdilution method. The results indicated a synergism between the antibiotics and the essential oil with a subinhibitory concentration (MIC/8, reducing the minimal inhibitory concentration (MIC sixteen times against the multidrug-resistant strains of S. aureus 358, E. coli 27 and P. aeruginosa 143, but none modulatory activity was observed against P. aeruginosa 78 and P. aeruginosa 91 strains. By our results, can be concluded that the essential oil of Cymbopogon citratus can be an interesting source of natural products with antibacterial and/or modulatory antibiotic activitieAVALIAÇÃO DA ATIVIDADE ANTIBACTERIANA E MODULADORA DE AMINOGLICOSÍDEOS DO ÓLEO ESSENCIAL DE Cymbopogon citratus (DC. STAPFVários trabalhos vêm demonstrando a importância do estudo de produtos naturais como fonte alternativa para novos antimicrobianos ou que venham potencializar os já existentes. Neste contexto este trabalho teve como objetivo investigar a atividade antibacteriana e as possíveis interações entre o óleo essencial de Cymbopogon citratus combinados a aminoglicosídeos frente a linhagens padrões e multirresistentes de S. aureus, E. coli e de P. aeruginosa provenientes de isolados clínicos. Um ensaio de microdiluição foi realizado para verificar a atividade antibacteriana e as possíveis interacções entre o produto natural e os antibióticos, utilizando uma concentração sub-inibitória. Através dos resultados foi constatado a interferência sinérgica dos

  16. Electrospray Ion Trap Mass Spectrometry and Chromatographic Behavior of the FDNB-Derivatized Products of Eight Aminoglycoside Antibiotics%8种氨基糖苷类抗生素FDNB衍生化产物的电喷雾离子阱质谱及色谱行为研究

    Institute of Scientific and Technical Information of China (English)

    周茂金; 梅如冰; 苏美英

    2011-01-01

    antibiotics were investigated by LC-MS/MS and HPLC-UV. CONCLUSION The structural information of the FDNB- derivatized products of aminoglycoside antibiotics was obtained via collision-activated dissociation, which provided a sound basis for the structural elucidation of the FDNB-derivatized products of aminoglycoside antibiotics and development of analytical methods ( LC-MS/ MS and HPLC-UV) of aminoglycoside compounds.

  17. 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.

  18. Resonance Rayleigh scattering and resonance non-linear scattering method for the determination of aminoglycoside antibiotics with water solubility CdS quantum dots as probe

    Science.gov (United States)

    Liu, Zhengwen; Liu, Shaopu; Wang, Lei; Peng, Juanjuan; He, Youqiu

    2009-09-01

    In pH 6.6 Britton-Robinson buffer medium, the CdS quantum dots capped by thioglycolic acid could react with aminoglycoside (AGs) antibiotics such as neomycin sulfate (NEO) and streptomycin sulfate (STP) to form the large aggregates by virtue of electrostatic attraction and the hydrophobic force, which resulted in a great enhancement of resonance Rayleigh scattering (RRS) and resonance non-linear scattering such as second-order scattering (SOS) and frequency doubling scattering (FDS). The maximum scattering peak was located at 310 nm for RRS, 568 nm for SOS and 390 nm for FDS, respectively. The enhancements of scattering intensity (Δ I) were directly proportional to the concentration of AGs in a certain ranges. A new method for the determination of trace NEO and STP using CdS quantum dots probe was developed. The detection limits (3 σ) were 1.7 ng mL -1 (NEO) and 4.4 ng mL -1 (STP) by RRS method, were 5.2 ng mL -1 (NEO) and 20.9 ng mL -1 (STP) by SOS method and were 4.4 ng mL -1 (NEO) and 25.7 ng mL -1 (STP) by FDS method, respectively. The sensitivity of RRS method was the highest. The optimum conditions and influence factors were investigated. In addition, the reaction mechanism was discussed.

  19. Activation of PI3K signaling prevents aminoglycoside-induced hair cell death in the murine cochlea

    Directory of Open Access Journals (Sweden)

    Azadeh Jadali

    2016-06-01

    Full Text Available Loss of sensory hair cells of the inner ear due to aminoglycoside exposure is a major cause of hearing loss. Using an immortalized multipotent otic progenitor (iMOP cell line, specific signaling pathways that promote otic cell survival were identified. Of the signaling pathways identified, the PI3K pathway emerged as a strong candidate for promoting hair cell survival. In aging animals, components for active PI3K signaling are present but decrease in hair cells. In this study, we determined whether activated PI3K signaling in hair cells promotes survival. To activate PI3K signaling in hair cells, we used a small molecule inhibitor of PTEN or genetically ablated PTEN using a conditional knockout animal. Hair cell survival was challenged by addition of gentamicin to cochlear cultures. Hair cells with activated PI3K signaling were more resistant to aminoglycoside-induced hair cell death. These results indicate that increased PI3K signaling in hair cells promote survival and the PI3K signaling pathway is a target for preventing aminoglycoside-induced hearing loss.

  20. Liposome-encapsulated aminoglycosides in pre-clinical and clinical studies

    NARCIS (Netherlands)

    R.M. Schiffelers (Raymond); G. Storm (Gert); I.A.J.M. Bakker-Woudenberg (Irma)

    2001-01-01

    textabstractLiposome-encapsulated amikacin has recently entered clinical trials. The rationale for liposome encapsulation of aminoglycosides is the possibility to increase the therapeutic index of this class of antibiotics by increasing aminoglycoside concentrations at the site of

  1. Prevalence of Aminoglycoside Resistance Genes in Acinetobacter baumannii Isolates

    OpenAIRE

    Aliakbarzade, Katayun; Farajnia, Safar; Karimi Nik, Ashraf; Zarei, Farzaneh; Tanomand, Asghar

    2014-01-01

    Background: Acinetobacter baumannii is one of the major causes of nosocomial infections and is resistant to most available antibiotics. Aminoglycosides remain as drugs of choice for treatment of Acinetobacter infections yet resistance to aminoglycosides has increased in the recent years. Objectives: The present study investigated the prevalence of genes encoding aminoglycoside-modifying enzymes in A. baumannii strains isolated from patients of Tabriz city, northwest of Iran. Materials and Met...

  2. Study of Pseudomonas Aeroginosa resistance to Penicillines, Cephalosporins and Aminoglycosides

    Directory of Open Access Journals (Sweden)

    Maleknezhad P

    1998-07-01

    Full Text Available Drug therapy and prophylaxy in infectious diseases, from hygienic and economical point of view, are very important. Infections caused by pseudomonas aeroginosa were particularly severe, with high mortality rates. In the recent years pseudomonas aeroginosa continued to cause the most severe, life-thereating infections in burned patients, in spite of the introduction of a wide variety of antibiotics advised specifically for their anti pseudomonal activity. The aim of this study, in which many cases of ps.aeroginosa infections are assessed is to identify the drug resistance of this bacteria to penicillines, cephalosporins and aminoglycosides by antibiotic sensitivity test (disk ager diffusion. Results as percent of resistance to each antibiotic were 89% to carbenicillin, 55% to piperacillin, 89% to mezlocillin, 89.5% to ticarcillin+clavulonic acid, 85% to ceftriaxone, 95% to tobramycin, 5% of all isolates were not sensitive to any antibiotics.

  3. Riboswitch control of induction of aminoglycoside resistance acetyl and adenyl-transferases.

    Science.gov (United States)

    He, Weizhi; Zhang, Xuhui; Zhang, Jun; Jia, Xu; Zhang, Jing; Sun, Wenxia; Jiang, Hengyi; Chen, Dongrong; Murchie, Alastair I H

    2013-08-01

    The acquisition of antibiotic resistance by human pathogens poses a significant threat to public health. The mechanisms that control the proliferation and expression of antibiotic resistance genes are not yet completely understood. The aminoglycosides are a historically important class of antibiotics that were introduced in the 1940s. Aminoglycoside resistance is conferred most commonly through enzymatic modification of the drug or enzymatic modification of the target rRNA through methylation or through the overexpression of efflux pumps. In our recent paper, we reported that expression of the aminoglycoside resistance genes encoding the aminoglycoside acetyl transferase (AAC) and aminoglycoside adenyl transferase (AAD) enzymes was controlled by an aminoglycoside-sensing riboswitch RNA. This riboswitch is embedded in the leader RNA of the aac/aad genes and is associated with the integron cassette system. The leader RNA can sense and bind specific aminoglycosides such that the binding causes a structural transition in the leader RNA, which leads to the induction of aminoglycoside antibiotic resistance. Specific aminoglycosides induce reporter gene expression mediated by the leader RNA. Aminoglycoside RNA binding was measured directly and, aminoglycoside-induced changes in RNA structure monitored by chemical probing. UV cross-linking and mutational analysis identified potential aminoglycoside binding sites on the RNA.

  4. Electrostatic interactions in aminoglycoside-RNA complexes.

    Science.gov (United States)

    Kulik, Marta; Goral, Anna M; Jasiński, Maciej; Dominiak, Paulina M; Trylska, Joanna

    2015-02-03

    Electrostatic interactions often play key roles in the recognition of small molecules by nucleic acids. An example is aminoglycoside antibiotics, which by binding to ribosomal RNA (rRNA) affect bacterial protein synthesis. These antibiotics remain one of the few valid treatments against hospital-acquired infections by Gram-negative bacteria. It is necessary to understand the amplitude of electrostatic interactions between aminoglycosides and their rRNA targets to introduce aminoglycoside modifications that would enhance their binding or to design new scaffolds. Here, we calculated the electrostatic energy of interactions and its per-ring contributions between aminoglycosides and their primary rRNA binding site. We applied either the methodology based on the exact potential multipole moment (EPMM) or classical molecular mechanics force field single-point partial charges with Coulomb formula. For EPMM, we first reconstructed the aspherical electron density of 12 aminoglycoside-RNA complexes from the atomic parameters deposited in the University at Buffalo Databank. The University at Buffalo Databank concept assumes transferability of electron density between atoms in chemically equivalent vicinities and allows reconstruction of the electron densities from experimental structural data. From the electron density, we then calculated the electrostatic energy of interaction using EPMM. Finally, we compared the two approaches. The calculated electrostatic interaction energies between various aminoglycosides and their binding sites correlate with experimentally obtained binding free energies. Based on the calculated energetic contributions of water molecules mediating the interactions between the antibiotic and rRNA, we suggest possible modifications that could enhance aminoglycoside binding affinity.

  5. Engineering persister-specific antibiotics with synergistic antimicrobial functions.

    Science.gov (United States)

    Schmidt, Nathan W; Deshayes, Stephanie; Hawker, Sinead; Blacker, Alyssa; Kasko, Andrea M; Wong, Gerard C L

    2014-09-23

    Most antibiotics target growth processes and are ineffective against persister bacterial cells, which tolerate antibiotics due to their reduced metabolic activity. These persisters act as a genetic reservoir for resistant mutants and constitute a root cause of antibiotic resistance, a worldwide problem in human health. We re-engineer antibiotics specifically for persisters using tobramycin, an aminoglycoside antibiotic that targets bacterial ribosomes but is ineffective against persisters with low metabolic and cellular transport activity. By giving tobramycin the ability to induce nanoscopic negative Gaussian membrane curvature via addition of 12 amino acids, we transform tobramycin itself into a transporter sequence. The resulting molecule spontaneously permeates membranes, retains the high antibiotic activity of aminoglycosides, kills E. coli and S. aureus persisters 4-6 logs better than tobramycin, but remains noncytotoxic to eukaryotes. These results suggest a promising paradigm to renovate traditional antibiotics.

  6. 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....

  7. CHEMICALLY FABRICATED SILVER NANOPARTICLES ENHANCES THE ACTIVITY OF ANTIBIOTICS AGAINST SELECTED HUMAN BACTERIAL PATHOGENS

    Directory of Open Access Journals (Sweden)

    S. Thangapandiyan and P. Prema*

    2012-05-01

    Full Text Available Due to the outbreak of infectious diseases caused by different pathogenic bacteria and the development of antibiotic resistance, the pharmaceutical companies and the researchers are now searching for new unconventional antibacterial agents. Nanotechnology represents a modern and innovative approach to develop new formulations based on metallic nanoparticles with antimicrobial properties. The potential bioactivity of chemically fabricated silver nanoparticles has been extensively studied. However, the antibacterial activity of silver nanoparticles individually or in combination with different antibiotics has not been demonstrated. In the present investigations, the effect of silver nanoparticles on the antibacterial activity of different antibiotics was evaluated against selected human bacterial pathogens such as Staphylococcus aureus, Streptococcus epidermis, Escherichia coli, Pseudomonas aeruginosa, and Bacillus cereus by disc diffusion method. In the presence of sub - inhibitory concentration of silver nanoparticles (100µL/disc, the antibacterial activities of all antibiotics are increased from 1 mm to 10 mm. The maximum fold increase was noticed for vancomycin against Pseudomonas aeruginosa (66.67%, Escherichia coli (62.50%, and Staphylococcus aureus (46% followed by rifampicin against Bacillus cereus (66.67% and kanamycin against Streptococcus epidermis (25%. These results signify that the silver nanoparticles showed potential antibacterial action of ß-lactams, glycopeptides, aminoglycosides, sulphonamides suggesting a possible utilization of silver nanocompounds in combination therapy against selected pathogens used in the experiment.

  8. Active controlled studies in antibiotic drug development.

    Science.gov (United States)

    Dane, Aaron

    2011-01-01

    The increasing concern of antibacterial resistance has been well documented, as has the relative lack of antibiotic development. This paradox is in part due to challenges with clinical development of antibiotics. Because of their rapid progression, untreated bacterial infections are associated with significant morbidity and mortality. As a consequence, placebo-controlled studies of new agents are unethical. Rather, pivotal development studies are mostly conducted using non-inferiority designs versus an active comparator. Further, infections because of comparator-resistant isolates must usually be excluded from the trial programme. Unfortunately, the placebo-controlled data classically used in support of non-inferiority designs are largely unavailable for antibiotics. The only available data are from the 1930s and 1940s and their use is associated with significant concerns regarding constancy and assay sensitivity. Extended public debate on this challenge has led to proposed solutions by some in which these concerns are addressed by using very conservative approaches to trial design, endpoints and non-inferiority margins, in some cases leading to potentially impractical studies. To compound this challenge, different Regulatory Authorities seem to be taking different approaches to these key issues. If harmonisation does not occur, antibiotic development will become increasingly challenging, with the risk of further decreases in the amount of antibiotic drug development. However with clarity on Regulatory requirements and an ability to feasibly conduct global development programmes, it should be possible to bring much needed additional antibiotics to patients.

  9. A non-sequence-specific requirement for SMN protein activity: the role of aminoglycosides in inducing elevated SMN protein levels.

    Science.gov (United States)

    Wolstencroft, Elizabeth C; Mattis, Virginia; Bajer, Anna A; Young, Philip J; Lorson, Christian L

    2005-05-01

    Spinal muscular atrophy (SMA) is caused by homozygous loss of the survival motor neuron (SMN1) gene. In virtually all SMA patients, a nearly identical copy gene is present, SMN2. SMN2 cannot fully compensate for the loss of SMN1 because the majority of transcripts derived from SMN2 lack a critical exon (exon 7), resulting in a dysfunctional SMN protein. Therefore, the critical distinction between a functional and a dysfunctional SMN protein is the inclusion or the exclusion of the exon 7 encoded peptide. To determine the role of the 16 amino acids encoded by SMN exon 7, a panel of synthetic mutations were transiently expressed in SMA patient fibroblasts and HeLa cells. Consistent with previous reports, the protein encoded by SMN exons 1-6 was primarily restricted to the nucleus. However, a variety of heterologous sequences fused to the C-terminus of SMN exons 1-6 allowed mutant SMN proteins to properly distribute to the cytoplasm and to the nuclear gems. These data demonstrate that the SMN exon 7 sequence is not specifically required, rather this region functions as a non-specific 'tail' that facilitates proper localization. Therefore, a possible means to restore additional activity to the SMNDelta7 protein could be to induce a longer C-terminus by suppressing recognition of the native stop codon. To address this possibility, aminoglycosides were examined for their ability to restore detectable levels of SMN protein in SMA patient fibroblasts. Aminoglycosides can suppress the accurate identification of translation termination codons in eukaryotic cells. Consistent with this, treatment of SMA patient fibroblasts with tobramycin and amikacin resulted in a quantitative increase in SMN-positive gems and an overall increase in detectable SMN protein. Taken together, this work describes the role of the critical exon 7 region and identifies a possible alternative approach for therapeutic intervention.

  10. Aminoglycoside-Resistant Bacteria and Rational Selection for Antibiotic-Producing Strain%细菌对氨基糖苷类抗生素的耐药性与抗生素产生菌的推理选育

    Institute of Scientific and Technical Information of China (English)

    陈代杰; 李燕

    2001-01-01

    The mechanisms of aminoglycoside-resistant bacteria including inactive enzymes and ribosome or ribosomal protein modification are briefly reviewed. The rational selection for antibiotic-produ-cing strain according to its resistant mechanisms is also discussed.%简要阐述氨基糖苷类抗生素耐药菌通过产生各种钝化酶来修饰活性分子的耐药机制,以及由抗生素作用靶位核糖体或核蛋白发生改变产生的耐药机制。同时,对抗生素产生菌的耐药机制以及利用这些机制进行抗生素产生菌推理选育也作了介绍。

  11. Antibiotic therapy for inducible AmpC β-lactamase-producing Gram-negative bacilli: what are the alternatives to carbapenems, quinolones and aminoglycosides?

    Science.gov (United States)

    Harris, P N A; Ferguson, J K

    2012-10-01

    Some bacteria that possess chromosomally determined AmpC β-lactamases may express these enzymes at a high level following exposure to β-lactams, either by induction or selection for derepressed mutants. This may lead to clinical failure even if an isolate initially tests susceptible in vitro, a phenomenon best characterised by third-generation cephalosporin therapy for Enterobacter bacteraemia or meningitis. Several other Enterobacteriaceae, such as Serratia marcescens, Citrobacter freundii, Providencia spp. and Morganella morganii (often termed the 'ESCPM' group), may also express high levels of AmpC. However, the risk of clinical failure with β-lactams that test susceptible in vitro is less clear in these species than for Enterobacter. Laboratories frequently do not report β-lactam or β-lactamase inhibitor combination drug susceptibilities for ESCPM organisms, encouraging alternative therapy with quinolones, aminoglycosides or carbapenems. However, quinolones and carbapenems present problems with selective pressure for multiresistant organisms, and aminoglycosides with potential toxicity. The risk of emergent AmpC-mediated resistance for non-Enterobacter spp. appears rare in clinical studies. Piperacillin/tazobactam may remain effective and may be less selective for AmpC derepressed mutants than cephalosporins. The potential roles for agents such as cefepime or trimethoprim/sulfamethoxazole are also discussed. Clinical studies that better define optimal treatment for this group of bacteria are required.

  12. Multiple strategies to activate gold nanoparticles as antibiotics

    Science.gov (United States)

    Zhao, Yuyun; Jiang, Xingyu

    2013-08-01

    Widespread antibiotic resistance calls for new strategies. Nanotechnology provides a chance to overcome antibiotic resistance by multiple antibiotic mechanisms. This paper reviews the progress in activating gold nanoparticles with nonantibiotic or antibiotic molecules to combat bacterial resistance, analyzes the gap between experimental achievements and real clinical application, and suggests some potential directions in developing antibacterial nanodrugs.

  13. Pharmacokinetics of Aminoglycosides

    Institute of Scientific and Technical Information of China (English)

    Lokangu Lombo(Congo); HE Hua

    2004-01-01

    The Pharmacokinetics informations of aminoglycosides, their monograph and clinical Pharmacokinetics parameters are reported in this review. The Aminoglycosides are highly polarity and in reserve for serious infections caused by aerobic gram-negative bacteria and some gram-positive bacteria but their toxicity are major limitations in clinical use.

  14. Rapid analysis of aminoglycoside antibiotics in bovine tissues using disposable pipette extraction and ultrahigh performance liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Lehotay, Steven J; Mastovska, Katerina; Lightfield, Alan R; Nuñez, Alberto; Dutko, Terry; Ng, Chilton; Bluhm, Louis

    2013-10-25

    A high-throughput qualitative screening and identification method for 9 aminoglycosides of regulatory interest has been developed, validated, and implemented for bovine kidney, liver, and muscle tissues. The method involves extraction at previously validated conditions, cleanup using disposable pipette extraction, and analysis by a 3 min ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. The drug analytes include neomycin, streptomycin, dihydrosptreptomycin, and spectinomycin, which have residue tolerances in bovine in the US, and kanamicin, gentamicin, apramycin, amikacin, and hygromycin, which do not have US tolerances established in bovine tissues. Tobramycin was used as an internal standard. An additional drug, paromomycin also was validated in the method, but it was dropped during implementation due to conversion of neomycin into paromomycin. Proposed fragmentation patterns for the monitored ions of each analyte were elucidated with the aid of high resolution MS using a quadrupole-time-of-flight instrument. Recoveries from spiking experiments at regulatory levels of concern showed that all analytes averaged 70-120% recoveries in all tissues, except hygromycin averaged 61% recovery. Lowest calibrated levels were as low as 0.005 μg/g in matrix extracts, which approximately corresponded to the limit of detection for screening purposes. Drug identifications at levels <0.05 μg/g were made in spiked and/or real samples for all analytes and tissues tested. Analyses of 60 samples from 20 slaughtered cattle previously screened positive for aminoglycosides showed that this method worked well in practice. The UHPLC-MS/MS method has several advantages compared to the previous microbial inhibition screening assay, especially for distinguishing individual drugs from a mixture and improving identification of gentamicin in tissue samples.

  15. Mitochondrial DNA Mutations Associated with Aminoglycoside Ototoxicity

    Institute of Scientific and Technical Information of China (English)

    GUAN Min-Xin

    2006-01-01

    The mitochondrial 12S rRNA has been shown to be the hot spot for mutations associated with both aminoglycoside-induced and non-syndromic hearing loss. Of all the mutations, the homoplasmic A1555G and C1494T mutations at a highly conserved decoding region in the 12S rRNA have been associated with aminoglycoside-induced and non-syndromic hearing loss in many families worldwide. The A1555G or C1494T mutation is expected to form novel 1494C-G1555 or 1494U-A1555 base-pair at the highly conserved A-site of 12S rRNA. These transitions make the secondary structure of this RNA more closely resemble the corresponding region of bacterial 16S rRNA. Thus, the new U - A or G-C pair in 12S rRNA created by the C1494T or A1555G transition facilitates the binding of aminoglycosides, thereby accounting for the fact that the exposure to aminoglycosides can induce or worsen hearing loss in individuals carrying these mutations. Furthermore, the growth defect and impairment of mitochondrial translation were observed in cell lines carrying the A1555G or C1494T mutation in the presence of high concentration of aminoglycosides. In addition, nuclear modifier genes and mitochondrial haplotypes modulate the phenotypic manifestation of the A1555G and C1494T mutations. These observations provide the direct genetic and biochemical evidences that the A1555G or C1494T mutation is a pathogenic mtDNA mutation associated with aminoglycoside-induced and nonsyndromic hearing loss. Therefore, these data have been providing valuable information and technology to predict which individuals are at risk for ototoxicity, to improve the safety of aminoglycoside antibiotic therapy, and eventually to decrease the incidence of deafness.

  16. Extracellular DNA Shields against Aminoglycosides in Pseudomonas aeruginosa Biofilms

    DEFF Research Database (Denmark)

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

    2013-01-01

    , which are thought to be a source of extracellular DNA at sites of infections, increases the tolerance of P. aeruginosa biofilms toward aminoglycosides. Although biofilm-associated aminoglycoside tolerance recently has been linked to extracellular DNA-mediated activation of the pmr genes, we demonstrate...... that the aminoglycoside tolerance mediated by the presence of extracellular DNA is not caused by activation of the pmr genes in our P. aeruginosa biofilms but rather by a protective shield effect of the extracellular DNA....

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

    Science.gov (United States)

    TEIXEIRA, Bertinellys; RODULFO, Hectorina; CARREÑO, Numirin; GUZMÁN, Militza; SALAZAR, Elsa; DONATO, Marcos DE

    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. PMID:27007556

  18. 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.

  19. Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo

    Science.gov (United States)

    Matsui, Jonathan I.; Haque, Asim; Huss, David; Messana, Elizabeth P.; Alosi, Julie A.; Roberson, David W.; Cotanche, Douglas A.; Dickman, J. David; Warchol, Mark E.

    2003-01-01

    The sensory hair cells of the inner ear undergo apoptosis after acoustic trauma or aminoglycoside antibiotic treatment, causing permanent auditory and vestibular deficits in humans. Previous studies have demonstrated a role for caspase activation in hair cell death and ototoxic injury that can be reduced by concurrent treatment with caspase inhibitors in vitro. In this study, we examined the protective effects of caspase inhibition on hair cell death in vivo after systemic injections of aminoglycosides. In one series of experiments, chickens were implanted with osmotic pumps that administrated the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (zVAD) into inner ear fluids. One day after the surgery, the animals received a 5 d course of treatment with streptomycin, a vestibulotoxic aminoglycoside. Direct infusion of zVAD into the vestibule significantly increased hair cell survival after streptomycin treatment. A second series of experiments determined whether rescued hair cells could function as sensory receptors. Animals treated with streptomycin displayed vestibular system impairment as measured by a greatly reduced vestibulo-ocular response (VOR). In contrast, animals that received concurrent systemic administration of zVAD with streptomycin had both significantly greater hair cell survival and significantly increased VOR responses, as compared with animals treated with streptomycin alone. These findings suggest that inhibiting the activation of caspases promotes the survival of hair cells and protects against vestibular function deficits after aminoglycoside treatment.

  20. 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 ...

  1. 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.

  2. Versatility of Aminoglycosides and Prospects for Their Future

    OpenAIRE

    2003-01-01

    Aminoglycoside antibiotics have had a major impact on our ability to treat bacterial infections for the past half century. Whereas the interest in these versatile antibiotics continues to be high, their clinical utility has been compromised by widespread instances of resistance. The multitude of mechanisms of resistance is disconcerting but also illuminates how nature can manifest resistance when bacteria are confronted by antibiotics. This article reviews the most recent knowledge about the ...

  3. Endotoxemia-mediated inflammation potentiates aminoglycoside-induced ototoxicity

    Science.gov (United States)

    Koo, J.-W.; Quintanilla-Dieck, L.; Jiang, M.; Liu, J.; Urdang, Z. D.; Allensworth, J. J.; Cross, C. P.; Li, H.; Steyger, P. S.

    2015-01-01

    The ototoxic aminoglycoside antibiotics are essential to treat severe bacterial infections, particularly in neonatal intensive care units. Using a bacterial lipopolysaccharide (LPS) experimental model of sepsis, we tested whether LPS-mediated inflammation potentiates cochlear uptake of aminoglycosides and permanent hearing loss in mice. Using confocal microscopy and enzyme-linked immunosorbent assays, we found that low-dose LPS (endotoxemia) greatly increased cochlear concentrations of aminoglycosides and resulted in vasodilation of cochlear capillaries without inducing paracellular flux across the blood-labyrinth barrier (BLB), or elevating serum concentrations of the drug. Additionally, endotoxemia increased expression of both serum and cochlear inflammatory markers. These LPS-induced changes, classically mediated by Toll-like Receptor 4 (TLR4), were attenuated in TLR4-hyporesponsive mice. Multiday dosing with aminoglycosides during chronic endotoxemia induced greater hearing threshold shifts and sensory cell loss compared to mice without endotoxemia. Thus, endotoxemia-mediated inflammation enhanced aminoglycoside trafficking across the BLB, and potentiated aminoglycoside-induced ototoxicity. These data indicate that patients with severe infections are at greater risk of aminoglycoside-induced hearing loss than previously recognized. PMID:26223301

  4. Proteasome inhibitory activity of thiazole antibiotics

    OpenAIRE

    Pandit, Bulbul; Bhat, Uppoor; Andrei L Gartel

    2011-01-01

    Thiopeptides are sulfur containing highly modified macrocyclic antibiotics with a central pyridine/tetrapyridine/dehydropiperidine ring with up to three thiazole substituents on positions 2, 3 and 6. Thiazole antibiotics with central pyridine nucleus have a macrocyclic loop connecting thiazole rings at position 2 and 3 described as ring A. In addition antibiotics with central tetrahydropyridine nucleus have a quinaldic acid macrocycle also connected to thiazole on position 2 described as ring...

  5. Zebrafish model for the study on drug ototoxicity of aminoglycoside antibiotics%氨基糖苷类药物耳毒性的斑马鱼模型的研究

    Institute of Scientific and Technical Information of China (English)

    赵壮; 佟军威; 张靖溥; 游学甫; 蒋建东; 胡昌勤

    2011-01-01

    Aminoglycoside antibiotics, due to their strong antibacterial effects and broad antimicrobial spectra, have been very commonly used in clinical practice in the past half century. However, aminoglycoside antibiotics manifest severe ototoxicity and nephrotoxicity, and are one of top factors in hearing loss. In this study, three members of the aminoglycoside antibiotics family, gentamycin, neomycin and streptomycin, were chosen as the representatives to be investigated for their toxicity to the embryonic development and the larva hair cells in zebrafish, and also to their target genes associated with hearing-related genes. The results showed that: ① the lethal effect of all three drugs demonstrated a significant dependence on concentration, and the severity order of the lethal effect was streptomycin > neomycin > gentamycin; ② all the three drugs caused the larva trunk bending in resting state at 5 dpf (day past fertilization), probably due to their ototoxicity in the physical imbalance and postural abnormalities; ③ impairment and reducing of the hair cells were observed in all three cases of drug treatment; ④ four genes, eyal, val, otx2 and dlx6a, which play an important role in the development of hearingorgans, showed differential and significant decrease of gene expression in a drug concentration-dependent manner. This study for the first time reports the relevance between the expression of hearing genes and the three ototoxic antibiotics and also proved the feasibility of establishing a simple, accurate, intuitive and fast model with zebrafish for the detection of drug ototoxicity.%氨基糖苷类抗生素因其抗菌谱广、抗菌能力强,半个多世纪以来一直是临床上常用的抗菌素之一.但氨基糖苷类抗生素具有很强的耳毒和肾毒作用,在药物致聋因素中排在首位.本研究以庆大霉素(gentamycin)、新霉素(neomycin)、链霉素(streptomycin)等3种氨基糖苷类抗生素为代表性药物,研究其对斑马

  6. 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

    . 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...

  7. Aminoglycoside inhibition of Staphylococcus aureus biofilm formation is nutrient dependent.

    Science.gov (United States)

    Henry-Stanley, Michelle J; Hess, Donavon J; Wells, Carol L

    2014-06-01

    Biofilms represent microbial communities, encased in a self-produced matrix or extracellular polymeric substance. Microbial biofilms are likely responsible for a large proportion of clinically significant infections and the multicellular nature of biofilm existence has been repeatedly associated with antibiotic resistance. Classical in vitro antibiotic-susceptibility testing utilizes artificial growth media and planktonic microbes, but this method may not account for the variability inherent in environments subject to biofilm growth in vivo. Experiments were designed to test the hypothesis that nutrient concentration can modulate the antibiotic susceptibility of Staphylococcus aureus biofilms. Developing S. aureus biofilms initiated on surgical sutures, and in selected experiments planktonic cultures, were incubated for 16 h in 66 % tryptic soy broth, 0.2 % glucose (1× TSBg), supplemented with bactericidal concentrations of gentamicin, streptomycin, ampicillin or vancomycin. In parallel experiments, antibiotics were added to growth medium diluted one-third (1/3× TSBg) or concentrated threefold (3× TSBg). Following incubation, viable bacteria were enumerated from planktonic cultures or suture sonicates, and biofilm biomass was assayed using spectrophotometry. Interestingly, bactericidal concentrations of gentamicin (5 µg gentamicin ml(-1)) and streptomycin (32 µg streptomycin ml(-1)) inhibited biofilm formation in samples incubated in 1/3× or 1× TSBg, but not in samples incubated in 3× TSBg. The nutrient dependence of aminoglycoside susceptibility is not only associated with biofilm formation, as planktonic cultures incubated in 3× TSBg in the presence of gentamicin also showed antibiotic resistance. These findings appeared specific for aminoglycosides because biofilm formation was inhibited in all three growth media supplemented with bactericidal concentrations of the cell wall-active antibiotics, ampicillin and vancomycin. Additional experiments

  8. A preliminary report on the susceptibility to aminoglycosides of Escherichia coli isolated from the community-acquired urinary tract infections in adults in south-east Poland

    Directory of Open Access Journals (Sweden)

    Fidecka-Skwarzynska Magdalena

    2015-03-01

    Full Text Available World-wide, urinary tract infections (UTIs are an important clinical problem. In such, the most frequently isolated uropathogen is Escherichia coli. In the treatment of uncomplicated UTIs, e.g. cystitis, the widely used antibiotics are nitrofurantoin, trimethoprim/sulfamethoxazole, fosfomycin trometamol or ciprofloxacin, while the treatment of pyelonephritis requires the usage of antibiotics with a broader spectrum of activity, such as cephalosporins of the 3rd and 4th generation, aminoglycosides or even carbapenems. The aim of this study was to assess the susceptibility to aminoglycosides (such as amikacin, gentamicin, netilmicin and tobramycin of E. coli isolated from UTIs in adult community patients living in Lubelszczyzna. We found that all of the 86 strains of E. coli encountered were susceptible to amikacin. Moreover, the prevalence of susceptibility to tobramycin, gentamicin or netilmicin among the tested strains was found to be 89,5%, 90,7% or 94,2%, respectively. The data obtained in the present study shows the high susceptibility to aminoglycosides of E. coli isolated from the community-acquired UTIS in adults. These data, together with that derived from current literature, indicate that aminoglycosides, when employed in combination therapy with other antibiotics, may still be very useful group of antibacterial agents in the treatment of UTI’s in Poland.

  9. Design, synthesis, and antibacterial activities of neomycin-lipid conjugates: polycationic lipids with potent gram-positive activity.

    Science.gov (United States)

    Bera, Smritilekha; Zhanel, George G; Schweizer, Frank

    2008-10-01

    Aminoglycoside antibiotics and cationic detergents constitute two classes of clinically important drugs and antiseptics. Their bacteriological and clinical efficacy, however, has decreased recently due to antibiotic resistance. We have synthesized aminoglycoside-lipid conjugates in which the aminoglycoside neomycin forms the cationic headgroup of a polycationic detergent. Our results show that neomycin-C16 and neomycin-C20 conjugates exhibit strong Gram-positive activity but reduced Gram-negative activity. The MIC of neomycin-C16 (C20) conjugates against methicillin-resistant Staphylococcus aureus (MRSA) is comparable to clinically used antiseptics.

  10. Synergistic antibacterial activity of Curcumin with antibiotics against Staphylococcus aureus.

    Science.gov (United States)

    Teow, Sin-Yeang; Ali, Syed Atif

    2015-11-01

    This study evaluated the synergistic antibacterial activity of Curcumin with 8 different antibiotic groups. Two reference, one clinical and ten environmental strains of Staphylococcus aureus (S. aureus) were tested. Disc diffusion assay with 25 μg/mL Curcumin demonstrated synergism in combination with a majority of tested antibiotics against S. aureus. However, checkerboard micro dilution assay only showed synergism, fractional inhibitory concentration index (FICI) indifferent interactions but no antagonism was observed. In time-kill curve, appreciable reduction of bacterial cells was also observed in combination therapy (Curcumin + antibiotics) compared to monotherapy (Curcumin or antibiotic(s) alone). The antibiotics with higher synergistic interaction with Curcumin are arranged in a decreasing order: Amikacin > Gentamicin > Ciprofloxacin.

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

    OpenAIRE

    Edward eCunningham-Oakes; Odel eSoren; Caroline eMoussa; Getika eRathor; Yingjun eLiu; Anthony eCoates; Yanmin eHu

    2015-01-01

    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. ...

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

    OpenAIRE

    Cunningham-Oakes, Edward; Soren, Odel; Moussa, Caroline; Rathor, Getika; Liu, Yingjun; Coates, Anthony; Hu, Yanmin

    2015-01-01

    Infections caused by methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. 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 Trid...

  13. Burkholderia cepacia complex Phage-Antibiotic Synergy (PAS): antibiotics stimulate lytic phage activity.

    Science.gov (United States)

    Kamal, Fatima; Dennis, Jonathan J

    2015-02-01

    The Burkholderia cepacia complex (Bcc) is a group of at least 18 species of Gram-negative opportunistic pathogens that can cause chronic lung infection in cystic fibrosis (CF) patients. Bcc organisms possess high levels of innate antimicrobial resistance, and alternative therapeutic strategies are urgently needed. One proposed alternative treatment is phage therapy, the therapeutic application of bacterial viruses (or bacteriophages). Recently, some phages have been observed to form larger plaques in the presence of sublethal concentrations of certain antibiotics; this effect has been termed phage-antibiotic synergy (PAS). Those reports suggest that some antibiotics stimulate increased production of phages under certain conditions. The aim of this study is to examine PAS in phages that infect Burkholderia cenocepacia strains C6433 and K56-2. Bcc phages KS12 and KS14 were tested for PAS, using 6 antibiotics representing 4 different drug classes. Of the antibiotics tested, the most pronounced effects were observed for meropenem, ciprofloxacin, and tetracycline. When grown with subinhibitory concentrations of these three antibiotics, cells developed a chain-like arrangement, an elongated morphology, and a clustered arrangement, respectively. When treated with progressively higher antibiotic concentrations, both the sizes of plaques and phage titers increased, up to a maximum. B. cenocepacia K56-2-infected Galleria mellonella larvae treated with phage KS12 and low-dose meropenem demonstrated increased survival over controls treated with KS12 or antibiotic alone. These results suggest that antibiotics can be combined with phages to stimulate increased phage production and/or activity and thus improve the efficacy of bacterial killing.

  14. 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.

  15. DETERMINATION OF AMINOGLYCOSIDES IN FOOD BY FLUORESCENCE POLARIZATION IMMUNOASSAY

    Directory of Open Access Journals (Sweden)

    FARAFONOVA O.V.

    2015-01-01

    Full Text Available The methodic for quantitative determination of aminoglycoside antibiotics (gentamicin, kanamycin, streptomycin, amikacin, neomycin in food by polarization fluorescent immunoassay (FPIA is developed. The size and structure influence of a fluorescent molecule on a fluorescence polarization degree is analyzed. Affinity constants of antibodies to compounds and tracers were estimated, optimized working concentration of tracers and antibodies that provide the maximum value of analytical signal. Methods were tested in the antibiotics identification in milk, eggs and chicken.

  16. 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.

  17. 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.

  18. Influence of antibiotic adsorption on biocidal activities of silver nanoparticles.

    Science.gov (United States)

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

    2016-04-01

    Excessive use of antibiotics has posed two major challenges in public healthcare. One of them is associated with the development of multi-drug resistance while the other one is linked to side effects. In the present investigation, the authors report an innovative approach to tackle the challenges of multi-drug resistance and acute toxicity of antibiotics by using antibiotics adsorbed metal nanoparticles. Monodisperse silver nanoparticles (SNPs) have been synthesised by two-step process. In the first step, SNPs were prepared by chemical reduction of AgNO3 with oleylamine and in the second step, oleylamine capped SNPs were phase-transferred into an aqueous medium by ligand exchange. Antibiotics - tetracycline and kanamycin were further adsorbed on the surface of SNPs. Antibacterial activities of SNPs and antibiotic adsorbed SNPs have been investigated on gram-positive (Staphylococcus aureus, Bacillus megaterium, Bacillus subtilis), and gram-negative (Proteus vulgaris, Shigella sonnei, Pseudomonas fluorescens) bacterial strains. Synergistic effect of SNPs on antibacterial activities of tetracycline and kanamycin has been observed. Biocidal activity of tetracycline is improved by 0-346% when adsorbed on SNPs; while for kanamycin, the improvement is 110-289%. This synergistic effect of SNPs on biocidal activities of antibiotics may be helpful in reducing their effective dosages.

  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. 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.

  1. 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-ter...... mechanism for emergence of antibiotic resistance.......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......-term tolerance, respectively, to this drug class. Here, we show that chaperonin GroEL/GroES over-expression accelerates acquisition of streptomycin resistance and reduces susceptibility to several other antibiotics following sub-lethal streptomycin antibiotic exposure. Chaperonin buffering could provide a novel...

  2. Ablation of mixed lineage kinase 3 (Mlk3) does not inhibit ototoxicity induced by acoustic trauma or aminoglycoside exposure.

    Science.gov (United States)

    Polesskaya, Oksana; Cunningham, Lisa L; Francis, Shimon P; Luebke, Anne E; Zhu, Xiaoxia; Collins, David; Vasilyeva, Olga N; Sahler, Julie; Desmet, Emily A; Gelbard, Harris A; Maggirwar, Sanjay B; Walton, Joseph P; Frisina, Robert D; Dewhurst, Stephen

    2010-12-01

    Jun N-terminal kinase (JNK) is activated in cochlear hair cells following acoustic trauma or exposure to aminoglycoside antibiotics. Blockade of JNK activation using mixed lineage kinase (MLK) inhibitors prevents hearing loss and hair cell death following these stresses. Since current pharmacologic inhibitors of MLKs block multiple members of this kinase family, we examined the contribution of the major neuronal family member (MLK3) to stress-induced ototoxicity, usingMlk3(-/-) mice. Immunohistochemical staining revealed that MLK3 is expressed in cochlear hair cells of C57/BL6 mice (but not in Mlk3(-/-) animals). After exposure to acoustic trauma there was no significant difference in DPOAE and ABR values betweenMlk3(-/-) and wild-type mice at 48 h following exposure or 2 weeks later. Susceptibility of hair cells to aminoglycoside toxicity was tested by exposing explanted utricles to gentamicin. Gentamicin-induced hair cell death was equivalent in utricles from wild-type and Mlk3(-/-) mice. Blockade of JNK activation with the pharmacologic inhibitor SP600125 attenuated cell death in utricles from both wild-type and Mlk3(-/-) mice. These data show that MLK3 ablation does not protect against hair cell death following acoustic trauma or exposure to aminoglycoside antibiotics, suggesting that MLK3 is not the major upstream regulator of JNK-mediated hair cell death following these stresses. Rather, other MLK family members such as MLK1, which is also expressed in cochlea, may have a previously unappreciated role in noise- and aminoglycoside-induced ototoxicity.

  3. Contemporary antimicrobial activity of triple antibiotic ointment: a multiphased study of recent clinical isolates in the United States and Australia.

    Science.gov (United States)

    Jones, Ronald N; Li, Qing; Kohut, Bruce; Biedenbach, Douglas J; Bell, Jan; Turnidge, John D

    2006-01-01

    Triple antibiotic ointment (TAO) containing neomycin, polymyxin B, and bacitracin was launched in the 1950s in the United States (USA) as a prescription product and then was used over the counter (OTC) since the 1970s (USA) to prevent superficial wound infections. In Australia, TAO has been restricted to prescription use. This study 1) determined cross-resistance patterns of neomycin compared with other aminoglycosides; 2) determined the level and trend of resistance to TAO and individual components especially versus mupirocin-resistant strains (USA); and 3) established the baseline TAO activity level against pathogens from Australia. A total of 200 strains (> or =50% gentamicin-resistant) from the United States were used for the cross-resistance study including Staphylococcus aureus (110), coagulase-negative staphylococci (CoNS; 50), Pseudomonas aeruginosa (10), Escherichia coli (20), and other Enterobacteriaceae (10) tested against TAO, bacitracin, polymyxin B, neomycin, amikacin, gentamicin, streptomycin, tobramycin, and mupirocin. Fifty gentamicin-resistant isolates from each year (1997-2002) were used to determine the activity of TAO over time. Baseline resistance rates of TAO among 300 Australian isolates (AGARS Program, 2002-2003) were also studied. Reference broth microdilution methods were used in all phases of this study. At a 1:100 dilution of the ointment concentration, TAO inhibited all CoNS, Pseudomonas aeruginosa, and Enterobacteriaceae isolates, and resistance to TAO among Staphylococcus aureus at this concentration was only 5% in the cross-resistance study. Patterns of susceptibility in the United States did not significantly vary from 1997 to 2002. Australian pathogens showed that TAO was 98% active against methicillin-resistant Staphylococcus aureus and 100% for Enterobacteriaceae, methicillin-susceptible S. aureus, CoNS, and P. aeruginosa, the rates equivalent to those observed in the United States. Mupirocin-resistant S. aureus (5%) and Co

  4. A random sequential mechanism of aminoglycoside acetylation by Mycobacterium tuberculosis Eis protein.

    Directory of Open Access Journals (Sweden)

    Oleg V Tsodikov

    Full Text Available An important cause of bacterial resistance to aminoglycoside antibiotics is the enzymatic acetylation of their amino groups by acetyltransferases, which abolishes their binding to and inhibition of the bacterial ribosome. Enhanced intracellular survival (Eis protein from Mycobacterium tuberculosis (Mt is one of such acetyltransferases, whose upregulation was recently established as a cause of resistance to aminoglycosides in clinical cases of drug-resistant tuberculosis. The mechanism of aminoglycoside acetylation by MtEis is not completely understood. A systematic analysis of steady-state kinetics of acetylation of kanamycin A and neomycin B by Eis as a function of concentrations of these aminoglycosides and the acetyl donor, acetyl coenzyme A, reveals that MtEis employs a random-sequential bisubstrate mechanism of acetylation and yields the values of the kinetic parameters of this mechanism. The implications of these mechanistic properties for the design of inhibitors of Eis and other aminoglycoside acetyltransferases are discussed.

  5. Enzymology of aminoglycoside biosynthesis-deduction from gene clusters.

    Science.gov (United States)

    Wehmeier, Udo F; Piepersberg, Wolfgang

    2009-01-01

    The classical aminoglycosides are, with very few exceptions, typically actinobacterial secondary metabolites with antimicrobial activities all mediated by inhibiting translation on the 30S subunit of the bacterial ribosome. Some chemically related natural products inhibit glucosidases by mimicking oligo-alpha-1,4-glucosides. The biochemistry of the aminoglycoside biosynthetic pathways is still a developing field since none of the pathways has been analyzed to completeness as yet. In this chapter we treat the enzymology of aminoglycoside biosyntheses as far as it becomes apparent from recent investigations based on the availability of DNA sequence data of biosynthetic gene clusters for all major structural classes of these bacterial metabolites. We give a more general overview of the field, including descriptions of some key enzymes in various aminoglycoside pathways, whereas in Chapter 20 provides a detailed account of the better-studied enzymology thus far known for the neomycin and butirosin pathways.

  6. Metabolic Activity Interferometer: A Powerful Tool for Testing Antibiotics

    Directory of Open Access Journals (Sweden)

    Rachel R. P. Machado

    2012-01-01

    Full Text Available It is demonstrated that the efficiency of antibiotics can be tested using an interferometric method. Two antibiotics were used as models to show that an interferometric method to monitor the metabolic activity of slowly growing bacteria can be a safer method to judge antimicrobial properties of substances than conventional methods. The susceptibility of Mycobacterium bovis to hexane extract of Pterodon emarginatus and to the well-known antibiotic rifampicin was tested with the interferometric method and with the conventional microplate method. The microplate method revealed a potential activity of hexane extract against M. bovis. However, the interferometric method showed that the action of this substance is rather limited. Also in the case of rifampicin, the interferometric method was able to detect resistant bacteria.

  7. Indigenous and acquired modifications in the aminoglycoside binding sites of Pseudomonas aeruginosa rRNAs

    DEFF Research Database (Denmark)

    Gutierrez, Belen; Douthwaite, Stephen Roger; Gonzalez-Zorn, Bruno

    2013-01-01

    Aminoglycoside antibiotics remain the drugs of choice for treatment of Pseudomonas aeruginosa infections, particularly for respiratory complications in cystic-fibrosis patients. Previous studies on other bacteria have shown that aminoglycosides have their primary target within the decoding region......RNA molecules were methylated. The modification status of a virulent clinical strain expressing the acquired methyltransferase RmtD was altered in two important respects: RmtD stoichiometrically modified m (7)G1405 conferring high resistance to the aminoglycoside tobramycin and, in doing so, impeded one...

  8. [Antibiotic activity of P. aeruginosa against MRSA and Candida albicans].

    Science.gov (United States)

    Kondo, Shigemi; Sato, Naotake; Yamada, Toshihiko; Miyazaki, Sakiko; Oguri, Toyoko; Igari, Jun

    2002-04-01

    The antibiotic activity demonstrated by P. aeruginosa (Bacillus pyocyaneus) has been reported more than one hundred years ago by Emmerich et al (1899). Studies on such bacterial interference between P. aeruginosa and other pathogenic bacteria or fungi have not been extensively reported in recent years. In this paper, we report on the anti MRSA activity and anti Candida activity demonstrated by clinical isolates of P. aeruginosa (34 strains). The antibiotic activity was tested by reversed agar plate method, as previously reported, and the degree of the activity was expressed as the diameter of the zone of growth inhibition. The stability of both anti MRSA activity and anti Candida activity was evaluated at the time after 24 and 48-hr incubation. Also the effect of agar plate with or without 5% sheep blood on antibiotic activity was evaluated. Strong anti MRSA activity and anti Candida activity was shown at the time after 24-hr incubation. At the time after 48-hr incubation, anti MRSA activities were significantly suppressed but anti Candida activities were persisted. The inhibitory activity was correlated with dye production of P. aeruginosa. Some strains having non or weak dye production, showed the inhibitory activity by 48-hr incubation. Result from these strains without suppression of anti Candida activity by additional blood may suggest that the existence of a new factor produced by P. aeruginosa. Because of frequent isolation of MRSA or Candida from clinical materials, we must consider bacterial flora and bacterial interference against pathogenic bacteria at the time of the antibiotic choice for the patients infected or colonized with P. aeruginosa.

  9. 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.

  10. Aminoglycoside-Resistant Mutation of Pseudomonas aeruginosa Defective in Cytochrome c552 and Nitrate Reductase

    OpenAIRE

    Bryan, L E; Nicas, Thalia; Holloway, B W; Crowther, Carol

    1980-01-01

    A gentamicin-resistant mutant of Pseudomonas aeruginosa PAO503 was selected after ethyl methane sulfonate mutagenesis. The strain, P. aeruginosa PAO2401 had increased resistance to all aminoglycosides tested but exhibited no change for other antibiotics. The mutation designated aglA (aminoglycoside resistance) was 50% cotransducible with the 8-min ilvB,C marker on the P. aeruginosa chromosome. It showed a marked reduction in cytochrome c552 and nitrate reductase (Nar) and a change in terminal...

  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. Distribution, diversity, and activity of antibiotic-producing Pseudomonas spp.

    NARCIS (Netherlands)

    Souza, de J.T.

    2002-01-01

    Bacteria of the genus Pseudomonas are potential biocontrol agents of plant diseases caused by various fungi and oomycetes. Antibiotic production is an important trait responsible for the activity of several Pseudomonas strains against plant pathogens. Despite the amount of informati

  13. Inhibition of Aminoglycoside Acetyltransferase Resistance Enzymes by Metal Salts

    OpenAIRE

    2015-01-01

    Aminoglycosides (AGs) are clinically relevant antibiotics used to treat infections caused by both Gram-negative and Gram-positive bacteria, as well as Mycobacteria. As with all current antibacterial agents, resistance to AGs is an increasing problem. The most common mechanism of resistance to AGs is the presence of AG-modifying enzymes (AMEs) in bacterial cells, with AG acetyltransferases (AACs) being the most prevalent. Recently, it was discovered that Zn2+ metal ions displayed an inhibitory...

  14. Antibiotic inhibition of group I ribozyme function.

    Science.gov (United States)

    von Ahsen, U; Davies, J; Schroeder, R

    1991-09-26

    The discovery of catalytically active RNA has provided the basis for the evolutionary concept of an RNA world. It has been proposed that during evolution the functions of ancient catalytic RNA were modulated by low molecular weight effectors, related to antibiotics, present in the primordial soup. Antibiotics and RNA may have coevolved in the formation of the modern ribosome. Here we report that a set of aminoglycoside antibiotics, which are known to interact with the decoding region of the 16S ribosomal RNA of Escherichia coli, inhibit the second step of splicing of the T4 phage-derived td intron. Thus catalytic RNA seems to interact not only with a mononucleotide and an amino acid, but also with another class of biomolecules, the sugars. Splicing of other group I introns but not group II introns was inhibited. The similarity in affinity and specificity of these antibiotics for group I introns and rRNAs may result from recognition of evolutionarily conserved structures.

  15. 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.

  16. Anticancer, antioxidant and antibiotic activities of mushroom Ramaria flava.

    Science.gov (United States)

    Liu, Kun; Wang, Junli; Zhao, Le; Wang, Qian

    2013-08-01

    Ramaria flava is a species of edible mushroom with some bioactivity. The anticancer, antioxidant and antibiotic activities and chemical composition of R. flava ethanol extract (EE) were evaluated. The present study exhibited that the EE displayed the strongest inhibitory activity against tumor cell MDA-MB-231 with an IC50 value of 66.54 μg/mL in three tested tumor cell lines, and the inhibition percent was 71.66% at the concentration of 200 μg/mL (MTT assay). The total phenolic compounds varied among four fractions of the EE from 6.66 to 61.01 mg gallic acid equivalent (GAE) per g dry weight. Water fraction exhibited high DPPH and OH radical-scavenging activities with low IC50 values of 5.86 and 18.08 μg/mL, respectively. Meanwhile, three phenolic compounds from water fraction were also identified by HPLC. The antibiotic activities of the EE were evaluated against three microorganisms and three fungi strains by means of the agar well diffusion method and the poisoned medium technique, respectively. The EE also showed moderate antibiotic activities. These results suggest that R. flava could hold a good potential source for human health.

  17. 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...

  18. 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.

  19. Hepatocyte growth factor mimetic protects lateral line hair cells from aminoglycoside exposure

    Directory of Open Access Journals (Sweden)

    Phillip eUribe

    2015-01-01

    Full Text Available Loss of sensory hair cells from exposure to certain licit drugs (e.g., aminoglycoside antibiotics, platinum-based chemotherapy agents can result in permanent hearing loss. Here we ask if allosteric activation of the hepatocyte growth factor (HGF cascade via Dihexa, a small molecule drug candidate, can protect hair cells from aminoglycoside toxicity. Unlike native HGF, Dihexa is chemically stable and blood-brain barrier permeable. As a synthetic HGF mimetic, it forms a functional ligand by dimerizing with endogenous HGF to activate the HGF receptor and downstream signaling cascades. To evaluate Dihexa as a potential hair cell protectant, we used the larval zebrafish lateral line, which possesses hair cells that are homologous to mammalian inner ear hair cells and show similar responses to toxins. A dose-response relationship for Dihexa protection was established using two ototoxins, neomycin and gentamicin. We found that a Dihexa concentration of 1 µM confers optimal protection from acute treatment with either ototoxin. Pretreatment with Dihexa does not affect the amount of fluorescently tagged gentamicin that enters hair cells, indicating that Dihexa’s protection is likely mediated by intracellular events and not by inhibiting aminoglycoside entry. Dihexa-mediated protection is attenuated by co-treatment with the HGF antagonist 6-AH, further evidence that HGF activation is a component of the observed protection. Additionally, Dihexa’s robust protection is partially attenuated by co-treatment with inhibitors of the downstream HGF targets Akt, TOR and MEK. Addition of an amino group to the N-terminal of Dihexa also attenuates the protective response, suggesting that even small substitutions greatly alter the specificity of Dihexa for its target. Our data suggest that Dihexa confers protection of hair cells through an HGF-mediated mechanism and that Dihexa holds clinical potential for mitigating chemical ototoxicity.

  20. 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.

  1. High level aminoglycoside resistance and distribution of aminoglycoside resistant genes among clinical isolates of Enterococcus species in Chennai, India.

    Science.gov (United States)

    Padmasini, Elango; Padmaraj, R; Ramesh, S Srivani

    2014-01-01

    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.

  2. 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.

  3. Structural Analysis of a Putative Aminoglycoside N-Acetyltransferase from Bacillus anthracis

    Energy Technology Data Exchange (ETDEWEB)

    Klimecka, Maria M.; Chruszcz, Maksymilian; Font, Jose; Skarina, Tatiana; Shumilin, Igor; Onopryienko, Olena; Porebski, Przemyslaw J.; Cymborowski, Marcin; Zimmerman, Matthew D.; Hasseman, Jeremy; Glomski, Ian J.; Lebioda, Lukasz; Savchenko, Alexei; Edwards, Aled; Minor, Wladek (SC); (Toronto); (UV)

    2012-02-15

    For the last decade, worldwide efforts for the treatment of anthrax infection have focused on developing effective vaccines. Patients that are already infected are still treated traditionally using different types of standard antimicrobial agents. The most popular are antibiotics such as tetracyclines and fluoroquinolones. While aminoglycosides appear to be less effective antimicrobial agents than other antibiotics, synthetic aminoglycosides have been shown to act as potent inhibitors of anthrax lethal factor and may have potential application as antitoxins. Here, we present a structural analysis of the BA2930 protein, a putative aminoglycoside acetyltransferase, which may be a component of the bacterium's aminoglycoside resistance mechanism. The determined structures revealed details of a fold characteristic only for one other protein structure in the Protein Data Bank, namely, YokD from Bacillus subtilis. Both BA2930 and YokD are members of the Antibiotic-NAT superfamily (PF02522). Sequential and structural analyses showed that residues conserved throughout the Antibiotic-NAT superfamily are responsible for the binding of the cofactor acetyl coenzyme A. The interaction of BA2930 with cofactors was characterized by both crystallographic and binding studies.

  4. Microcalorimetric Study on the Antibiotic Activity of Clarithromycin and Erythromycin

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    By using LKB-2277 Bioactivity Monitoring System, the heat effect changes in the process of inhibitory action of clarithromycin and erythromycin on Escherichia coli at 37℃ were determined. Quantitative analysis showed that relationship between antibiotic concentration c and rate constant k of Escherichia coli growth, and half inhibitory ratio concentration ICs0: clarithromyein: k= 0. 030 03- 1. 1736 × 10-3c, 8. 45 mg ?L-1 ;erythromycin:k=0. 031 08-8. 4657?10-4c, 14. 45 mg ?L-1. As a result of the microcalorimetry experiments, it not only indicated that antibacterial activity of clarithromycin was stronger than that of ery0thromycin, but also reported the changeable features of thermodynamics of the bacterial cell in biological,biochemical and metabolic process under different drug action.

  5. 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.

  6. Aminoglycoside resistance in Haemophilus influenzae.

    Science.gov (United States)

    Gomez-Lus, R; Vergara, Y

    1995-04-01

    From September 1, 1990 to December 31, 1993 a total of 425 Haemophilus influenzae strains from clinical specimens were isolated in the Microbiology Laboratory of the Zaragoza University Hospital. Of these strains, 16 (33.33%) were resistant to kanamycin, neomycin, paromomycin, lividomycin and streptomycin. Demonstration of APH (3')-I activity by the phosphocellulose paper binding assay, based on the incorporation of radiolabel into lividomycin was sixfold greater than into butirosin. Two DNA probes were prepared to screen for the genes encoding APH(3') activity in kanamycin-resistant H. influenzae. Homology was observed between the aphA1 DNA probe and total cellular DNA from all 16 APH(3')-I producers. On the other hand, streptomycin-resistance was not through metabolic modification of the antibiotic.

  7. 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.

  8. A microcomputer spreadsheet for aminoglycoside kinetics.

    Science.gov (United States)

    Kiacz, B J

    1990-05-01

    Development of an aminoglycoside monitoring program need not entail large capital expenditures for pharmacokinetic software. Microsoft's Excel spreadsheet was used to develop a single compartment, first-order kinetics template for individualized aminoglycoside dosing. The formulas employed may be adapted to virtually any other microcomputer spreadsheet package to provide accurate professional results.

  9. Therapeutic drug monitoring of aminoglycosides in neonates

    NARCIS (Netherlands)

    Touw, Daniël J; Westerman, Elsbeth M; Sprij, Arwen J

    2009-01-01

    The efficacy and toxicity of aminoglycosides show a strong direct positive relationship with blood drug concentrations, therefore, therapy with aminoglycosides in adults is usually guided by therapeutic drug monitoring. Dosing regimens in adults have evolved from multiple daily dosing to extended-in

  10. 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...... alternative for combating pathogenic bacteria....

  11. Isolated deafness following recovery from neurologic injury and adult respiratory distress syndrome. A sequela of intercurrent aminoglycoside and diuretic use.

    Science.gov (United States)

    Lynn, A M; Redding, G J; Morray, J P; Tyler, D C

    1985-05-01

    We report two children who survived neurologic injury (near-drowning and Reye's syndrome) and adult respiratory distress syndrome and who required prolonged ventilatory support. Follow-up examination in both children showed steady neurologic recovery, but five months following discharge from their acute illness, profound hearing loss was diagnosed in both children. A review of the literature is reported and the hypothesis that combined aminoglycoside antibiotic and loop diuretic therapy caused the hearing loss is presented. Recommendation is made for audiologic assessment within six months of recovery from critical illness of pediatric patients in whom therapy has included loop diuretic and aminoglycoside antibiotic therapy.

  12. 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.

  13. 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.

  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.

  15. Identification of aminoglycoside resistance genes by Triplex PCR in Enterococcus spp. isolated from ICUs.

    Science.gov (United States)

    Mirnejad, Reza; Sajjadi, Nikta; Masoumi Zavaryani, Sara; Piranfar, Vahhab; Hajihosseini, Maryam; Roshanfekr, Maliheh

    2016-09-01

    Early detection of antibiotic-resistant enterococci is an important part of patient treatment. Therefore, the aim of the present study was to evaluate the resistance patterns and simultaneously identify and characterise the resistance genes in Enterococcus spp. using a triplex polymerase chain reaction (PCR) method. In all, 150 consecutive Enterococcus spp were collected from several hospitals in Tehran (Iran) from January to December 2015. The Enterococcus species were identified by standard phenotypic/biochemical tests and PCR. The antimicrobial resistance patterns were determined using a disk diffusion method. The triplex PCR method was designed to identify gentamicin and other aminoglycoside resistance genes. Among the 150 Enterococcus specimens, 87 cases (58%) were Enterococcus faecalis, and 63 cases (42%) were Enterococcus faecium. The highest frequency of resistance was observed for tetracycline while the lowest was found for vancomycin. Among the identified samples, 56.9% contained the aac(6')-Ie-aph(2'')-Ia gene, 22.2% contained the aph(3')-IIIa gene, and 38.8% contained the ant(4')-?a gene. Eight percent of the isolates contained the three aminoglycoside resistance genes. Data analysis showed that there was a significant correlation between the phenotypic gentamicin resistance and the presence of the aminoglycoside resistance genes (18.9%, p Enterococcus strains had increased aminoglycoside resistance. The direct correlation between resistance genes, such as the aminoglycoside resistance factor, and phenotypic resistance was not significant (p > 0.05).

  16. Research activities to improve the utilization of antibiotics in Africa.

    Science.gov (United States)

    Massele, Amos; Tiroyakgosi, Celda; Matome, Matshediso; Desta, Abayneh; Muller, Arno; Paramadhas, Bene D Anand; Malone, Brighid; Kurusa, Gobuiwang; Didimalang, Thatayaone; Moyo, Mosana; Godman, Brian

    2017-02-01

    There is a need to improve the rational use of antibiotics across continents including Africa. This has resulted in initiatives in Botswana including treatment guidelines and the instigation of Antibiotic Stewardship Programs (ASPs). The next steps involve a greater understanding of current antibiotic utilization and resistance patterns (AMR). This resulted in a 2-day meeting involving key stakeholders principally from Botswana to discuss key issues including AMR rates as well as ASPs in both the public and private sectors. Following this, the findings will be used to plan future studies across Africa including point prevalence studies. The findings will be presented in July 2016 at the next Medicines Utilization Research in Africa meeting will ideally serve as a basis for planning future pertinent interventional studies to enhance the rational use of antibiotics in Botswana and wider.

  17. The importance of active learning and practice on the students' mastery of pharmacokinetic calculations for the intermittent intravenous infusion dosing of antibiotics

    Directory of Open Access Journals (Sweden)

    Mehvar Reza

    2012-11-01

    Full Text Available Abstract Background Estimation of pharmacokinetic parameters after intermittent intravenous infusion (III of antibiotics, such as aminoglycosides or vancomycin, has traditionally been a difficult subject for students in clinical pharmacology or pharmacokinetic courses. Additionally, samples taken at different intervals during repeated dose therapy require manipulation of sampling times before accurate calculation of the patient-specific pharmacokinetic parameters. The main goal of this study was to evaluate the effectiveness of active learning tools and practice opportunities on the ability of students to estimate pharmacokinetic parameters from the plasma samples obtained at different intervals following intermittent intravenous infusion. Methods An extensive reading note, with examples, and a problem case, based on a patient’s chart data, were created and made available to students before the class session. Students were required to work through the case before attending the class. The class session was devoted to the discussion of the case requiring active participation of the students using a random participation program. After the class, students were given additional opportunities to practice the calculations, using online modules developed by the instructor, before submitting an online assignment. Results The performance of students significantly (P P  Conclusions Despite being a difficult subject, students achieve mastery of pharmacokinetic calculations for the topic of intermittent intravenous infusion when appropriate active learning strategies and practice opportunities are employed.

  18. Antibacterial activity of plant extracts and phytochemicals on antibiotic-resistant bacteria

    OpenAIRE

    Nascimento,Gislene G. F.; Locatelli,Juliana; Freitas,Paulo C.; Silva,Giuliana L.

    2000-01-01

    The antimicrobial activity of plant extracts and phytochemicals was evaluated with antibiotic susceptible and resistant microorganisms. In addition, the possible synergistic effects when associated with antibiotics were studied. Extracts from the following plants were utilized: Achillea millifolium (yarrow), Caryophyllus aromaticus (clove), Melissa offficinalis (lemon-balm), Ocimun basilucum (basil), Psidium guajava (guava), Punica granatum (pomegranate), Rosmarinus officinalis (rosemary), Sa...

  19. Mildiomycin: a nucleoside antibiotic that inhibits protein synthesis.

    Science.gov (United States)

    Feduchi, E; Cosín, M; Carrasco, L

    1985-03-01

    Mildiomycin, a new nucleoside antibiotic, selectively inhibits protein synthesis in HeLa cells, and is less active in the inhibition of RNA or DNA synthesis. An increased inhibition of translation by mildiomycin is observed in cultured HeLa cells when they are permeabilized by encephalomyocarditis virus. This observation suggests that this antibiotic does not easily pass through the cell membrane, as occurs with other nucleoside and aminoglycoside antibiotics. The inhibition of translation is also observed in cell-free systems, such as endogenous protein synthesis in a rabbit reticulocyte lysate or the synthesis of polyphenylalanine directed by poly (U). Finally the mode of action of mildiomycin was investigated and the results suggest that the compound blocks the peptidyl-transferase center.

  20. Silver nanoparticles strongly enhance and restore bactericidal activity of inactive antibiotics against multiresistant Enterobacteriaceae.

    Science.gov (United States)

    Panáček, Aleš; Smékalová, Monika; Večeřová, Renata; Bogdanová, Kateřina; Röderová, Magdaléna; Kolář, Milan; Kilianová, Martina; Hradilová, Šárka; Froning, Jens P; Havrdová, Markéta; Prucek, Robert; Zbořil, Radek; Kvítek, Libor

    2016-06-01

    Bacterial resistance to conventional antibiotics is currently one of the most important healthcare issues, and has serious negative impacts on medical practice. This study presents a potential solution to this problem, using the strong synergistic effects of antibiotics combined with silver nanoparticles (NPs). Silver NPs inhibit bacterial growth via a multilevel mode of antibacterial action at concentrations ranging from a few ppm to tens of ppm. Silver NPs strongly enhanced antibacterial activity against multiresistant, β-lactamase and carbapenemase-producing Enterobacteriaceae when combined with the following antibiotics: cefotaxime, ceftazidime, meropenem, ciprofloxacin and gentamicin. All the antibiotics, when combined with silver NPs, showed enhanced antibacterial activity at concentrations far below the minimum inhibitory concentrations (tenths to hundredths of one ppm) of individual antibiotics and silver NPs. The enhanced activity of antibiotics combined with silver NPs, especially meropenem, was weaker against non-resistant bacteria than against resistant bacteria. The double disk synergy test showed that bacteria produced no β-lactamase when treated with antibiotics combined with silver NPs. Low silver concentrations were required for effective enhancement of antibacterial activity against multiresistant bacteria. These low silver concentrations showed no cytotoxic effect towards mammalian cells, an important feature for potential medical applications.

  1. Performance evaluation of powdered activated carbon for removing 28 types of antibiotics from water.

    Science.gov (United States)

    Zhang, Xinbo; Guo, Wenshan; Ngo, Huu Hao; Wen, Haitao; Li, Nan; Wu, Wei

    2016-05-01

    Currently, the occurrence and fate of antibiotics in the aquatic environment has become a very serious problem in that they can potentially and irreversibly damage the ecosystem and human health. For this reason, interest has increased in developing strategies to remove antibiotics from water. This study evaluated the performance of powdered activated carbon (PAC) in removing from water 6 representative groups of 28 antibiotics, namely Tetracyclines (TCs), Macrolides (MCs), Chloramphenicols (CPs), Penicillins (PNs), Sulfonamides (SAs) and Quinolones (QNs). Results indicate that PAC demonstrated superior adsorption capacity for all selected antibiotics. The removal efficiency was up to 99.9% in deionized water and 99.6% in surface water at the optimum conditions with PAC dosage of 20 mg/L and contact time of 120 min. According to the Freundlich model's adsorption isotherm, the values of n varied among these antibiotics and most were less than 1, suggesting that the adsorption of antibiotics onto PAC was nonlinear. Adsorption of antibiotics followed well the pseudo-second-order kinetic model (R(2) = 0.99). Analysis using the Weber-Morris model revealed that the intra-particle diffusion was not the only rate-controlling step. Overall, the findings in this study confirm that PAC is a feasible and viable option for removing antibiotics from water in terms of water quality improvement and urgent antibiotics pollution control. Further research is essential on the following subjects: (i) removing more types of antibiotics by PAC; (ii) the adsorption process; and (iii) the mechanism of the competitive adsorption existing between natural organic matters (NOMs) and antibiotics.

  2. 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

  3. Study of the aminoglycoside subsistence phenotype of bacteria residing in the gut of humans and zoo animals

    Directory of Open Access Journals (Sweden)

    Teresita De Jesus eBello Gonzalez

    2016-01-01

    Full Text Available Recent studies indicate that next to antibiotic resistance, bacteria are able to subsist on antibiotics as a carbon source. Here we evaluated the potential of gut bacteria from healthy human volunteers and zoo animals to subsist on antibiotics. Nine gut isolates of Escherichia coli and Cellulosimicrobium spp. displayed increases in colony forming units during incubations in minimal medium with only antibiotics added, i.e. the antibiotic subsistence phenotype. Furthermore, laboratory strains of E. coli and Pseudomonas putida equipped with the aminoglycoside 3’phosphotransferase II gene also displayed the subsistence phenotype on aminoglycosides. In order to address which endogenous genes could be involved in these subsistence phenotypes, the broad-range glycosyl-hydrolase inhibiting iminosugar deoxynojirimycin (DNJ was used. Addition of DNJ to minimal medium containing glucose showed initial growth retardation of resistant E. coli, which was rapidly recovered to normal growth. In contrast, addition of DNJ to minimal medium containing kanamycin arrested resistant E. coli growth, suggesting that glycosyl-hydrolases were involved in the subsistence phenotype. However, antibiotic degradation experiments showed no reduction in kanamycin, even though the number of colony forming units increased. Although antibiotic subsistence phenotypes are readily observed in bacterial species, and are even found in susceptible laboratory strains carrying standard resistance genes, we conclude there is a discrepancy between the observed antibiotic subsistence phenotype and actual antibiotic degradation. Based on these results we can hypothesise that aminoglycoside modifying enzymes might first inactivate the antibiotic (i.e. by acetylation of amino groups, modification of hydroxyl groups by adenylation and phosphorylation respectively, before the subsequent action of catabolic enzymes. Even though we do not dispute that antibiotics could be used as a single carbon

  4. Molecular Epidemiology of Aminoglycosides Resistance in Acinetobacter Spp. with Emergence of Multidrug-Resistant Strains

    OpenAIRE

    MH Nazem Shirazi; Gh Shajari; R Kheltabadi Farahani; R Moniri; A Ghasemi

    2010-01-01

    Background: Acinetobacter spp. is characterized as an important nosocomial pathogen and increasing antimicrobial resistance. Our aim was to evaluate antimicrobial susceptibility and aminoglycosides resistance genes of Acinetobacter spp. isolated from hospitalized patients. Methods: Sixty isolates were identified as Acinetobacter species. The isolates were tested for antibiotic resistance by disc diffusion method for 12 antimicrobials. The presence of aphA6, aacC1 aadA1, and aadB genes were de...

  5. 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

    2015-03-11

    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.

  6. Antifungal activity and gene expression of lipopeptide antibiotics in strains of genus Bacillus

    OpenAIRE

    Grabova A. Yu.; Dragovoz I. V.; Zelena L. B.; Tkachuk D. M.; Avdeeva L. V.

    2016-01-01

    Aim. To research the antifungal activity and gene expression of lipopeptide antibiotics in strains of genus Bacillus. Methods. Deferred antagonism method, PCR, qRT-PCR, MALDI-TOF mass spectrometry. Results. It was revealed that Bacillus sp. strains C6 and Lg37s out of five tested strains had the highest antifungal activity. Based on the molecular genetic methods, it was shown that the expression of genes of lipopeptide antibiotics, related to the fengycin family, occurred in all these strains...

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

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    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.

  8. 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.

  9. Aminoglycoside resistance rates, phenotypes, and mechanisms of Gram-negative bacteria from infected patients in upper Egypt.

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    Gamal F Gad

    Full Text Available With the re-emergence of older antibiotics as valuable choices for treatment of serious infections, we studied the aminoglycoside resistance of Gram-negative bacteria isolated from patients with ear, urinary tract, skin, and gastrointestinal tract infections at Minia university hospital in Egypt. Escherichia coli (mainly from urinary tract and gastrointestinal tract infections was the most prevalent isolate (28.57%, followed by Pseudomonas aeruginosa (25.7% (mainly from ear discharge and skin infections. Isolates exhibited maximal resistance against streptomycin (83.4%, and minimal resistance against amikacin (17.7% and intermediate degrees of resistance against neomycin, kanamycin, gentamicin, and tobramycin. Resistance to older aminoglycosides was higher than newer aminoglycosides. The most common aminoglycoside resistance phenotype was that of streptomycin resistance, present as a single phenotype or in combination, followed by kanamycin-neomycin as determined by interpretative reading. The resistant Pseudomonas aeruginosa strains were capable of producing aminoglycoside-modifying enzymes and using efflux as mechanisms of resistance. Using checkerboard titration method, the most frequently-observed outcome in combinations of aminoglycosides with β-lactams or quinolones was synergism. The most effective combination was amikacin with ciprofloxacin (100% Synergism, whereas the least effective combination was gentamicin with amoxicillin (53.3% Synergistic, 26.7% additive, and 20% indifferent FIC indices. Whereas the studied combinations were additive and indifferent against few of the tested strains, antagonism was never observed. The high resistance rates to aminoglycosides exhibited by Gram-negative bacteria in this study could be attributed to the selective pressure of aminoglycoside usage which could be controlled by successful implementation of infection control measures.

  10. Aminoglycoside resistance rates, phenotypes, and mechanisms of Gram-negative bacteria from infected patients in upper Egypt.

    Science.gov (United States)

    Gad, Gamal F; Mohamed, Heba A; Ashour, Hossam M

    2011-02-17

    With the re-emergence of older antibiotics as valuable choices for treatment of serious infections, we studied the aminoglycoside resistance of Gram-negative bacteria isolated from patients with ear, urinary tract, skin, and gastrointestinal tract infections at Minia university hospital in Egypt. Escherichia coli (mainly from urinary tract and gastrointestinal tract infections) was the most prevalent isolate (28.57%), followed by Pseudomonas aeruginosa (25.7%) (mainly from ear discharge and skin infections). Isolates exhibited maximal resistance against streptomycin (83.4%), and minimal resistance against amikacin (17.7%) and intermediate degrees of resistance against neomycin, kanamycin, gentamicin, and tobramycin. Resistance to older aminoglycosides was higher than newer aminoglycosides. The most common aminoglycoside resistance phenotype was that of streptomycin resistance, present as a single phenotype or in combination, followed by kanamycin-neomycin as determined by interpretative reading. The resistant Pseudomonas aeruginosa strains were capable of producing aminoglycoside-modifying enzymes and using efflux as mechanisms of resistance. Using checkerboard titration method, the most frequently-observed outcome in combinations of aminoglycosides with β-lactams or quinolones was synergism. The most effective combination was amikacin with ciprofloxacin (100% Synergism), whereas the least effective combination was gentamicin with amoxicillin (53.3% Synergistic, 26.7% additive, and 20% indifferent FIC indices). Whereas the studied combinations were additive and indifferent against few of the tested strains, antagonism was never observed. The high resistance rates to aminoglycosides exhibited by Gram-negative bacteria in this study could be attributed to the selective pressure of aminoglycoside usage which could be controlled by successful implementation of infection control measures.

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

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    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.

  12. Molecular determinants of affinity for aminoglycoside binding to the aminoglycoside nucleotidyltransferase(2'')-Ia.

    Science.gov (United States)

    Wright, Edward; Serpersu, Engin H

    2006-08-29

    One of the most commonly occurring aminoglycoside resistance enzymes is aminoglycoside 2''-O-nucleotidyltransferase [ANT(2'')]. In the present study molecular determinants of affinity and specificity for aminoglycoside binding to this enzyme are investigated using isothermal titration calorimetry (ITC). Binding of aminoglycosides is enthalpically driven accompanied by negative entropy changes. The presence of metal-nucleotide increases the affinity for all but one of the aminoglycosides studied but has no effect on specificity. The substituents at positions 1, 2', and 6' are important determinants of substrate specificity. An amino group at these positions leads to greater affinity. No correlation is observed between the change in affinity and enthalpy. At the 2' position greater affinity results from a more negative enthalpy for an aminoglycoside containing an amino rather than a hydroxyl at that position. At the 6' position the greater affinity for an aminoglycoside containing an amino substituent results from a less disfavorable entropic contribution. The thermodynamic basis for the change in affinity at position 1 could not be determined because of the weak binding of one of the aminoglycoside substrates, amikacin. The effect of increasing osmotic stress on affinity was used to determine that a net release of approximately four water molecules occurs when tobramycin binds to ANT(2''). No measurable net change in the number of bound water molecules is observed when neomycin binds the enzyme. Data acquired in this work provide the rationale for the ability of ANT(2'') to confer resistance against kanamycins but not neomycins.

  13. Nosocomial infection and its molecular mechanisms of antibiotic resistance.

    Science.gov (United States)

    Xia, Jufeng; Gao, Jianjun; Tang, Wei

    2016-02-01

    Nosocomial infection is a kind of infection, which is spread in various hospital environments, and leads to many serious diseases (e.g. pneumonia, urinary tract infection, gastroenteritis, and puerperal fever), and causes higher mortality than community-acquired infection. Bacteria are predominant among all the nosocomial infection-associated pathogens, thus a large number of antibiotics, such as aminoglycosides, penicillins, cephalosporins, and carbapenems, are adopted in clinical treatment. However, in recent years antibiotic resistance quickly spreads worldwide and causes a critical threat to public health. The predominant bacteria include Methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii. In these bacteria, resistance emerged from antibiotic resistant genes and many of those can be exchanged between bacteria. With technical advances, molecular mechanisms of resistance have been gradually unveiled. In this review, recent advances in knowledge about mechanisms by which (i) bacteria hydrolyze antibiotics (e.g. extended spectrum β-lactamases, (ii) AmpC β-lactamases, carbapenemases), (iii) avoid antibiotic targeting (e.g. mutated vanA and mecA genes), (iv) prevent antibiotic permeation (e.g. porin deficiency), or (v) excrete intracellular antibiotics (e.g. active efflux pump) are summarized.

  14. 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.

  15. Aminoglycoside nephrotoxicity: modeling, simulation, and control.

    Science.gov (United States)

    Rougier, Florent; Claude, Daniel; Maurin, Michel; Sedoglavic, Alexandre; Ducher, Michel; Corvaisier, Stéphane; Jelliffe, Roger; Maire, Pascal

    2003-03-01

    The main constraints on the administration of aminoglycosides are the risks of nephrotoxicity and ototoxicity, which can lead to acute, renal, vestibular, and auditory toxicities. In the present study we focused on nephrotoxicity. No reliable predictor of nephrotoxicity has been found to date. We have developed a deterministic model which describes the pharmacokinetic behavior of aminoglycosides (with a two-compartment model), the kinetics of aminoglycoside accumulation in the renal cortex, the effects of aminoglycosides on renal cells, the resulting effects on renal function by tubuloglomerular feedback, and the resulting effects on serum creatinine concentrations. The pharmacokinetic parameter values were estimated by use of the NPEM program. The estimated pharmacodynamic parameter values were obtained after minimization of the least-squares objective function between the measured and the calculated serum creatinine concentrations. A simulation program assessed the influences of the dosage regimens on the occurrence of nephrotoxicity. We have also demonstrated the relevancy of modeling of the circadian rhythm of the renal function. We have shown the ability of the model to fit with 49 observed serum creatinine concentrations for a group of eight patients treated for endocarditis by comparison with 49 calculated serum creatinine concentrations (r(2) = 0.988; P < 0.001). We have found that for the same daily dose, the nephrotoxicity observed with a thrice-daily administration schedule appears more rapidly, induces a greater decrease in renal function, and is more prolonged than those that occur with less frequent administration schedules (for example, once-daily administration). Moreover, for once-daily administration, we have demonstrated that the time of day of administration can influence the incidence of aminoglycoside nephrotoxicity. The lowest level of nephrotoxicity was observed when aminoglycosides were administered at 1:30 p.m. Clinical application of this

  16. Bactericidal Antibiotics Induce Toxic Metabolic Perturbations that Lead to Cellular Damage.

    Science.gov (United States)

    Belenky, Peter; Ye, Jonathan D; Porter, Caroline B M; Cohen, Nadia R; Lobritz, Michael A; Ferrante, Thomas; Jain, Saloni; Korry, Benjamin J; Schwarz, Eric G; Walker, Graham C; Collins, James J

    2015-11-03

    Understanding how antibiotics impact bacterial metabolism may provide insight into their mechanisms of action and could lead to enhanced therapeutic methodologies. Here, we profiled the metabolome of Escherichia coli after treatment with three different classes of bactericidal antibiotics (?-lactams, aminoglycosides, quinolones). These treatments induced a similar set of metabolic changes after 30 min that then diverged into more distinct profiles at later time points. The most striking changes corresponded to elevated concentrations of central carbon metabolites, active breakdown of the nucleotide pool, reduced lipid levels, and evidence of an elevated redox state. We examined potential end-target consequences of these metabolic perturbations and found that antibiotic-treated cells exhibited cytotoxic changes indicative of oxidative stress, including higher levels of protein carbonylation, malondialdehyde adducts, nucleotide oxidation, and double-strand DNA breaks. This work shows that bactericidal antibiotics induce a complex set of metabolic changes that are correlated with the buildup of toxic metabolic by-products.

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

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    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.

  18. Extracellular DNA Acidifies Biofilms and Induces Aminoglycoside Resistance in Pseudomonas aeruginosa.

    Science.gov (United States)

    Wilton, Mike; Charron-Mazenod, Laetitia; Moore, Richard; Lewenza, Shawn

    2015-11-09

    Biofilms consist of surface-adhered bacterial communities encased in an extracellular matrix composed of DNA, exopolysaccharides, and proteins. Extracellular DNA (eDNA) has a structural role in the formation of biofilms, can bind and shield biofilms from aminoglycosides, and induces antimicrobial peptide resistance mechanisms. Here, we provide evidence that eDNA is responsible for the acidification of Pseudomonas aeruginosa planktonic cultures and biofilms. Further, we show that acidic pH and acidification via eDNA constitute a signal that is perceived by P. aeruginosa to induce the expression of genes regulated by the PhoPQ and PmrAB two-component regulatory systems. Planktonic P. aeruginosa cultured in exogenous 0.2% DNA or under acidic conditions demonstrates a 2- to 8-fold increase in aminoglycoside resistance. This resistance phenotype requires the aminoarabinose modification of lipid A and the production of spermidine on the bacterial outer membrane, which likely reduce the entry of aminoglycosides. Interestingly, the additions of the basic amino acid L-arginine and sodium bicarbonate neutralize the pH and restore P. aeruginosa susceptibility to aminoglycosides, even in the presence of eDNA. These data illustrate that the accumulation of eDNA in biofilms and infection sites can acidify the local environment and that acidic pH promotes the P. aeruginosa antibiotic resistance phenotype.

  19. In vitro activity of certain antibiotics against dermatophytes.

    Science.gov (United States)

    Dixit, A K; Kushwaha, R K

    1990-01-01

    The in vitro effect of antibiotics i.e. Hamycin, Griseofulvin and Mycostatin against Microsporum gypseum and M. fulvum showed that hamycin was comparatively less inhibitory to M. fulvum. Complete inhibition in mycelial growth and sporulation of these two dermatophytes was observed by Mycostatin at its 1000 micrograms/ml conc. after 8 days. M. fulvum did not sporulate at higher concentration of griseofulvin. However, griseofulvin completely inhibited the sporulation in M. gypseum at all the concentration of this drug, but mycelial growth of M. fulvum and M. gypseum were significantly inhibited. Mycostatin was found more inhibitory to these dermatophytes in comparison to hamycin and griseofulvin.

  20. 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.

    . Numerous reports of emerging Vancomycin resistance in some of the MRSA isolates have also been recorded (2,3). The prospect for a major antibiotic emergency is well recapitulated by the Infectious Diseases Society of America (IDSA) (4,5) which reports...-resistant Staphylococcus aureus isolate from a patient in Pennsylvania. Antimicrob. Agents Chemother. 48:275–280. 4. Infectious Diseases Society of America. 2010. The 10 X ’20 initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020...

  1. 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.

  2. 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.

  3. [Study on composition, antibiotic activity and antioxidant activity of volatile oils from uyghur medicine Althaea rosea].

    Science.gov (United States)

    Munira, Abudukeremu; Muheta'er, Tu'erhong; Resalat, Yimin; Xia, Na

    2015-04-01

    Althaea rosea is a type of mallow plant. Its dry flowers are one of common herb in Uyghur medicines and recorded to have several efficacies such as external application for detumescence, moistening lung and arresting cough, sweating and relieving asthma, diminishing swelling and promoting eruption, soothing the nerves and strengthening heart. However, there are only fewer studies on effective components of A. rosea and no literature about its volatile oil and pharmacological activity. In this paper, the volatile oil of A. rosea was obtained by using the chemical distillation and extraction method. The individual chemical components were separated from the volatile oil and identified by the Gas Chromatograph-Mass Spectrometer technique (GC-MS). The antioxidant activity against free radicals was detected by the'ultraviolet and visible spectrophotometer method. The antibiotic activity was detected by the filter paper diffusion method. The experimental results showed nearly 70 compounds in the volatile oil, with complex chemical components. With a low content, most of the compounds were aromatic and aliphatic compounds and their derivatives. A. rosea had a better antibiotic activity for common microorganisms, with a wide antibacterial spectrum. According to the results, the volatile oil of A. rosea will have a good application value in medicine, food and cosmetic industries, which provided a scientific basis for the development of natural A. rosea resources.

  4. Chronopharmacokinetics of once daily dosed aminoglycosides in hospitalized infectious patients

    NARCIS (Netherlands)

    van Maarseveen, Erik; Man, Wai Hong; Proost, Johannes; Neef, Cees; Touw, Daniël

    2015-01-01

    BACKGROUND: hospitalized patients with serious infections treated with aminoglycosides are at risk of developing nephrotoxicity. Previous clinical studies have shown that the pharmacokinetics of aminoglycosides in humans follow a circadian rhythm. Therefore, the time of administration could have imp

  5. Chronopharmacokinetics of once daily dosed aminoglycosides in hospitalized infectious patients

    NARCIS (Netherlands)

    van Maarseveen, Erik; Man, Wai Hong; Proost, Johannes; Neef, Cees; Touw, Daniel

    2015-01-01

    Background hospitalized patients with serious infections treated with aminoglycosides are at risk of developing nephrotoxicity. Previous clinical studies have shown that the pharmacokinetics of aminoglycosides in humans follow a circadian rhythm. Therefore, the time of administration could have impo

  6. Antibiotic resistance in Escherichia coli strains isolated from Antarctic bird feces, water from inside a wastewater treatment plant, and seawater samples collected in the Antarctic Treaty area

    Science.gov (United States)

    Rabbia, Virginia; Bello-Toledo, Helia; Jiménez, Sebastián; Quezada, Mario; Domínguez, Mariana; Vergara, Luis; Gómez-Fuentes, Claudio; Calisto-Ulloa, Nancy; González-Acuña, Daniel; López, Juana; González-Rocha, Gerardo

    2016-06-01

    Antibiotic resistance is a problem of global concern and is frequently associated with human activity. Studying antibiotic resistance in bacteria isolated from pristine environments, such as Antarctica, extends our understanding of these fragile ecosystems. Escherichia coli strains, important fecal indicator bacteria, were isolated on the Fildes Peninsula (which has the strongest human influence in Antarctica), from seawater, bird droppings, and water samples from inside a local wastewater treatment plant. The strains were subjected to molecular typing with pulsed-field gel electrophoresis to determine their genetic relationships, and tested for antibiotic susceptibility with disk diffusion tests for several antibiotic families: β-lactams, quinolones, aminoglycosides, tetracyclines, phenicols, and trimethoprim-sulfonamide. The highest E. coli count in seawater samples was 2400 cfu/100 mL. Only strains isolated from seawater and the wastewater treatment plant showed any genetic relatedness between groups. Strains of both these groups were resistant to β-lactams, aminoglycosides, tetracycline, and trimethoprim-sulfonamide.In contrast, strains from bird feces were susceptible to all the antibiotics tested. We conclude that naturally occurring antibiotic resistance in E. coli strains isolated from Antarctic bird feces is rare and the bacterial antibiotic resistance found in seawater is probably associated with discharged treated wastewater originating from Fildes Peninsula treatment plants.

  7. Synergistic antibacterial activity of Salvia officinalis and Cichorium intybus extracts and antibiotics.

    Science.gov (United States)

    Stefanović, Olgica D; Stanojević, Dragana D; Comić, Ljiljana R

    2012-01-01

    Synergistic activity of Salvia officinalis and Cichorium intybus extracts and commonly used antibiotics, amoxicillin and chloramphenicol, were evaluated. Interactions between plant extracts and antibiotics were tested by checkerboard method and interpreted as FIC index. Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853 and clinical isolates Staphylococcus aureus, Bacillus subtilis, Enterobacter cloacae, Klebsiella pneumoniae, Escherichia coli and Proteus mirabilis were used. Salvia officinalis showed better synergistic capacity than Cichorium intybus. Synergistic interactions were observed between amoxicillin and acetone or ethyl acetate extract of Salvia officinalis and between chloramphenicol and ethyl acetate extract of Salvia officinalis. In the presence of sub-inhibitory concentration (1/4 MIC to 1/32 MIC) of sage extracts, the MIC values of antibiotics were decreased by 2- to 10-fold. Synergism was observed against all test bacteria, except Escherichia coli. The combinations of acetone and ethyl acetate extract from Cichorium intybus and antibiotics resulted in additive and indifferent effects against tested bacteria.

  8. Pyrrolnitrin from Burkholderia cepacia: antibiotic activity against fungi and novel activities against streptomycetes.

    Science.gov (United States)

    el-Banna, N; Winkelmann, G

    1998-07-01

    A bacterial strain identified as Burkholderia cepacia NB-1 was isolated from water ponds in the botanical garden in Tübingen, Germany, and was found to produce a broad spectrum phenylpyrrole antimicrobial substance active against filamentous fungi, yeasts and Gram-positive bacteria. In batch culture containing glycerol and L-glutamic acid, the isolate NB-1 produced the antibiotic optimally late in the growth phase and accumulated a main portion in their cells. Isolation and purification of the antibiotic from Burkholderia (Pseudomonas) cepacia NB-1 by acetone extraction, gel filtration on Sephadex LH-20 and preparative HPLC yielded 0.54 mg l-1 of a pure substance. Spectroscopic data (HPLC, MS and NMR) confirmed that the compound was pyrrolnitrin [3-chloro-4-(2'-nitro-3'-chloro-phenyl) pyrrole]. Pyrrolnitrin has an inhibitory effect on the electron transport system, as demonstrated by isolated mitochondria from Neurospora crassa 74 A. This inhibition was relieved by N,N,N',N'-tetramethyl-p-phenylenediamine dihydrochloride (TMPD), indicating that pyrrolnitrin blocked the electron transfer between the dehydrogenases and the cytochrome components of the respiratory chain. Among Gram-positive bacteria, pyrrolnitrin was most active against certain Streptomyces species, especially S. antibioticus, which has not previously been described in the literature. In the presence of pyrrolnitrin, aerial mycelium and spore formation of Strep. antibioticus was suppressed, although growth continued via substrate mycelium. The new findings of inhibition of streptomycetes and their secondary metabolism by pyrrolnitrin may contribute to the fact that Pseudomonas species predominate in soil and compete even with antibiotic-producing Streptomyces.

  9. The aminoglycoside resistance methyltransferases from the ArmA/Rmt family operate late in the 30S ribosomal biogenesis pathway.

    Science.gov (United States)

    Zarubica, Tamara; Baker, Matthew R; Wright, H Tonie; Rife, Jason P

    2011-02-01

    Bacterial resistance to 4,6-type aminoglycoside antibiotics, which target the ribosome, has been traced to the ArmA/RmtA family of rRNA methyltransferases. These plasmid-encoded enzymes transfer a methyl group from S-adenosyl-L-methionine to N7 of the buried G1405 in the aminoglycoside binding site of 16S rRNA of the 30S ribosomal subunit. ArmA methylates mature 30S subunits but not 16S rRNA, 50S, or 70S ribosomal subunits or isolated Helix 44 of the 30S subunit. To more fully characterize this family of enzymes, we have investigated the substrate requirements of ArmA and to a lesser extent its ortholog RmtA. We determined the Mg+² dependence of ArmA activity toward the 30S ribosomal subunits and found that the enzyme recognizes both low Mg+² (translationally inactive) and high Mg+² (translationally active) forms of this substrate. We tested the effects of LiCl pretreatment of the 30S subunits, initiation factor 3 (IF3), and gentamicin/kasugamycin resistance methyltransferase (KsgA) on ArmA activity and determined whether in vivo derived pre-30S ribosomal subunits are ArmA methylation substrates. ArmA failed to methylate the 30S subunits generated from LiCl washes above 0.75 M, despite the apparent retention of ribosomal proteins and a fully mature 16S rRNA. From our experiments, we conclude that ArmA is most active toward the 30S ribosomal subunits that are at or very near full maturity, but that it can also recognize more than one form of the 30S subunit.

  10. Presence and biological activity of antibiotics used in fuel ethanol and corn co-product production.

    Science.gov (United States)

    Compart, D M Paulus; Carlson, A M; Crawford, G I; Fink, R C; Diez-Gonzalez, F; Dicostanzo, A; Shurson, G C

    2013-05-01

    Antibiotics are used in ethanol production to control bacteria from competing with yeast for nutrients during starch fermentation. However, there is no published scientific information on whether antibiotic residues are present in distillers grains (DG), co-products from ethanol production, or whether they retain their biological activity. Therefore, the objectives of this study were to quantify concentrations of various antibiotic residues in DG and determine whether residues were biologically active. Twenty distillers wet grains and 20 distillers dried grains samples were collected quarterly from 9 states and 43 ethanol plants in the United States. Samples were analyzed for DM, CP, NDF, crude fat, S, P, and pH to describe the nutritional characteristics of the samples evaluated. Samples were also analyzed for the presence of erythromycin, penicillin G, tetracycline, tylosin, and virginiamycin M1, using liquid chromatography and mass spectrometry. Additionally, virginiamycin residues were determined, using a U.S. Food and Drug Administration-approved bioassay method. Samples were extracted and further analyzed for biological activity by exposing the sample extracts to 10(4) to 10(7) CFU/mL concentrations of sentinel bacterial strains Escherichia coli ATCC 8739 and Listeria monocytogenes ATCC 19115. Extracts that inhibited bacterial growth were considered to have biological activity. Physiochemical characteristics varied among samples but were consistent with previous findings. Thirteen percent of all samples contained low (≤1.12 mg/kg) antibiotic concentrations. Only 1 sample extract inhibited growth of Escherichia coli at 10(4) CFU/mL, but this sample contained no detectable concentrations of antibiotic residues. No extracts inhibited Listeria monocytogenes growth. These data indicate that the likelihood of detectable concentrations of antibiotic residues in DG is low; and if detected, they are found in very low concentrations. The inhibition in only 1 DG

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

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    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.

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

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    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.

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

    Science.gov (United States)

    DiSpirito, Alan A.; Zahn, James A.; Graham, David W.; Kim, Hyung J.; Alterman, Michail; Larive, Cynthia

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

    NARCIS (Netherlands)

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

    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

  15. Systematically Altering Bacterial SOS Activity under Stress Reveals Therapeutic Strategies for Potentiating Antibiotics.

    Science.gov (United States)

    Mo, Charlie Y; Manning, Sara A; Roggiani, Manuela; Culyba, Matthew J; Samuels, Amanda N; Sniegowski, Paul D; Goulian, Mark; Kohli, Rahul M

    2016-01-01

    The bacterial SOS response is a DNA damage repair network that is strongly implicated in both survival and acquired drug resistance under antimicrobial stress. The two SOS regulators, LexA and RecA, have therefore emerged as potential targets for adjuvant therapies aimed at combating resistance, although many open questions remain. For example, it is not well understood whether SOS hyperactivation is a viable therapeutic approach or whether LexA or RecA is a better target. Furthermore, it is important to determine which antimicrobials could serve as the best treatment partners with SOS-targeting adjuvants. Here we derived Escherichia coli strains that have mutations in either lexA or recA genes in order to cover the full spectrum of possible SOS activity levels. We then systematically analyzed a wide range of antimicrobials by comparing the mean inhibitory concentrations (MICs) and induced mutation rates for each drug-strain combination. We first show that significant changes in MICs are largely confined to DNA-damaging antibiotics, with strains containing a constitutively repressed SOS response impacted to a greater extent than hyperactivated strains. Second, antibiotic-induced mutation rates were suppressed when SOS activity was reduced, and this trend was observed across a wider spectrum of antibiotics. Finally, perturbing either LexA or RecA proved to be equally viable strategies for targeting the SOS response. Our work provides support for multiple adjuvant strategies, while also suggesting that the combination of an SOS inhibitor with a DNA-damaging antibiotic could offer the best potential for lowering MICs and decreasing acquired drug resistance. IMPORTANCE Our antibiotic arsenal is becoming depleted, in part, because bacteria have the ability to rapidly adapt and acquire resistance to our best agents. The SOS pathway, a widely conserved DNA damage stress response in bacteria, is activated by many antibiotics and has been shown to play central role in

  16. Genome-scale identification method applied to find cryptic aminoglycoside resistance genes in Pseudomonas aeruginosa.

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    Julie M Struble

    Full Text Available BACKGROUND: The ability of bacteria to rapidly evolve resistance to antibiotics is a critical public health problem. Resistance leads to increased disease severity and death rates, as well as imposes pressure towards the discovery and development of new antibiotic therapies. Improving understanding of the evolution and genetic basis of resistance is a fundamental goal in the field of microbiology. RESULTS: We have applied a new genomic method, Scalar Analysis of Library Enrichments (SCALEs, to identify genomic regions that, given increased copy number, may lead to aminoglycoside resistance in Pseudomonas aeruginosa at the genome scale. We report the result of selections on highly representative genomic libraries for three different aminoglycoside antibiotics (amikacin, gentamicin, and tobramycin. At the genome-scale, we show significant (p<0.05 overlap in genes identified for each aminoglycoside evaluated. Among the genomic segments identified, we confirmed increased resistance associated with an increased copy number of several genomic regions, including the ORF of PA5471, recently implicated in MexXY efflux pump related aminoglycoside resistance, PA4943-PA4946 (encoding a probable GTP-binding protein, a predicted host factor I protein, a delta 2-isopentenylpyrophosphate transferase, and DNA mismatch repair protein mutL, PA0960-PA0963 (encoding hypothetical proteins, a probable cold shock protein, a probable DNA-binding stress protein, and aspartyl-tRNA synthetase, a segment of PA4967 (encoding a topoisomerase IV subunit B, as well as a chimeric clone containing two inserts including the ORFs PA0547 and PA2326 (encoding a probable transcriptional regulator and a probable hypothetical protein, respectively. CONCLUSIONS: The studies reported here demonstrate the application of new a genomic method, SCALEs, which can be used to improve understanding of the evolution of antibiotic resistance in P. aeruginosa. In our demonstration studies, we

  17. Antibiotic-functionalized graphite nanofibers and applications of cyanoglycosides in graphite nanofiber functionalization

    Science.gov (United States)

    Rotella, Madeline

    The synthesis of functionalized graphite nanofibers (GNFs) with antibiotics and cyclic boronate esters is described. By first oxidizing the GNFs, surface oxides are introduced to the fiber that serve as sites for the attachment of larger molecules such as aminoglycoside antibiotics and carbohydrates. On the one hand, the aminoglycoside antibiotic tobramycin can be attached to the surface of a GNF via the carboxyl groups. This tobramycin-labeled GNF was prepared, characterized for its antibiotic content by X-ray photoelectron spectroscopy (XPS), and studied for its retention of antibacterial activity against the common bacterium Pseudomonas aeruginosa. On the other hand, Boc-protected amine precursors which may serve as key intermediates in the preparation of a reversible GNF label were prepared starting from two similar carbohydrate substrates, tri-O-acetyl-D-galactal and tri-O-acetyl-D-glucal. A nitrile group was added to the C1 of the substrate via Ferrier addition with trimethylsilyl cyanide followed by reduction of the C2-C3 double bond and finally a deacylation to yield stereoisomeric diol nitriles. The diol nitriles in both series were converted to analogous protected Boc amines. Products were characterized by 1H and 13C NMR spectroscopy, mass spectrometry and X-ray crystallography.

  18. 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.

  19. 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.

  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, Laura J. [Stanford Synchrotron Radiation Laboratory, Stanford University, Menlo Park, CA 94025 (United States); Badarau, Adriana; Vakulenko, Sergei B. [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)

    2008-02-01

    APH(2′′)-Ic is an enzyme that is responsible for high-level gentamicin resistance in E. gallinarum isolates. Crystals of the wild-type enzyme and three mutants have been prepared and a complete X-ray diffraction data set was collected to 2.15 Å resolution from an F108L crystal. 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′′-phosphotransferase-Ic [APH(2′′)-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′′)-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 Å, β = 108.8°. X-ray diffraction data were collected to approximately 2.15 Å resolution from an F108L crystal at beamline BL9-2 at SSRL, Stanford, California, USA.

  1. Synergistic effect and antibiofilm activity between the antimicrobial peptide coprisin and conventional antibiotics against opportunistic bacteria.

    Science.gov (United States)

    Hwang, In-sok; Hwang, Jae-Sam; Hwang, Ji Hong; Choi, Hyemin; Lee, Eunjung; Kim, Yangmee; Lee, Dong Gun

    2013-01-01

    Coprisin is a 43-mer defensin-like peptide from the dung beetle, Copris tripartitus. In this study, we tested its minimum inhibitory concentration and performed combination assays to confirm the antibacterial susceptibility of coprisin and synergistic effects with antibiotics. The synergistic effects were evaluated by testing the effects of coprisin in combination with ampicillin, vancomycin, and chloramphenicol. The results showed that coprisin possessed antibacterial properties and had synergistic activities with the antibiotics. To understand the synergistic mechanism(s), we conducted hydroxyl radical assays. Coprisin alone and in combination with antibiotics generated hydroxyl radicals, which are highly reactive oxygen forms and the major property of bactericidal agents. Furthermore, the antibiofilm effect of coprisin alone and in combination with antibiotics was investigated. Biofilm formation is the source of many relentless and chronic bacterial infections. The results indicated that coprisin alone and in combination with antibiotics also had antibiofilm activity. Therefore, we conclude that coprisin has the potential to be used as a combinatorial therapeutic agent for the treatment of infectious diseases caused by bacteria.

  2. Structural basis for dual nucleotide selectivity of aminoglycoside 2''-phosphotransferase IVa provides insight on determinants of nucleotide specificity of aminoglycoside kinases.

    Science.gov (United States)

    Shi, Kun; Berghuis, Albert M

    2012-04-13

    Enzymatic phosphorylation through a family of enzymes called aminoglycoside O-phosphotransferases (APHs) is a major mechanism by which bacteria confer resistance to aminoglycoside antibiotics. Members of the APH(2″) subfamily are of particular clinical interest because of their prevalence in pathogenic strains and their broad substrate spectra. APH(2″) enzymes display differential preferences between ATP or GTP as the phosphate donor, with aminoglycoside 2″-phosphotransferase IVa (APH(2″)-IVa) being a member that utilizes both nucleotides at comparable efficiencies. We report here four crystal structures of APH(2″)-IVa, two of the wild type enzyme and two of single amino acid mutants, each in complex with either adenosine or guanosine. Together, these structures afford a detailed look at the nucleoside-binding site architecture for this enzyme and reveal key elements that confer dual nucleotide specificity, including a solvent network in the interior of the nucleoside-binding pocket and the conformation of an interdomain linker loop. Steady state kinetic studies, as well as sequence and structural comparisons with members of the APH(2″) subfamily and other aminoglycoside kinases, rationalize the different substrate preferences for these enzymes. Finally, despite poor overall sequence similarity and structural homology, analysis of the nucleoside-binding pocket of APH(2″)-IVa shows a striking resemblance to that of eukaryotic casein kinase 2 (CK2), which also exhibits dual nucleotide specificity. These results, in complement with the multitude of existing inhibitors against CK2, can serve as a structural basis for the design of nucleotide-competitive inhibitors against clinically relevant APH enzymes.

  3. In vitro effect of levofloxacin and vancomycin combination against high level aminoglycoside-resistant enterococci.

    Science.gov (United States)

    Erdem, Ilknur; Cicek-Senturk, Gonul; Yucesoy-Dede, Behiye; Yuksel-Kocdogan, Funda; Yuksel, Saim; Karagul, Emin

    2004-01-01

    The in vitro effects of levofloxacin and vancomycin in combination were evaluated against high level aminoglycoside-resistant (HLAR) enterococci using chequerboard and time-kill curve techniques. We examined 28 strains of enterococci comprising 17 Enterococcus faecalis, 10 E. faecium and one E. durans. The combination of vancomycin and levofloxacin had indifferent activity against all isolates according to chequerboard microdilution method, but was synergistic for two isolates, one E. faecium and one E. faecalis, using the time-kill curve method. Both strains were levofloxacin resistant and had high level aminoglycoside resistance to gentamicin and streptomycin. Antagonism was not detected in any strain. The results of this study suggested that the combination of vancomycin with levofloxacin does not often show synergistic effect against high level aminoglycoside-resistant enterococci.

  4. In vitro activity of antibiotics alone and in combination against Actinobacillus actinomycetemcomitans.

    Science.gov (United States)

    Yogev, R; Shulman, D; Shulman, S T; Glogowski, W G

    1986-01-01

    The MICs for 90% of the organisms tested (MIC90S) of 11 antibiotics against 24 clinical isolates of Actinobacillus actinomycetemcomitans were determined by the MIC 2000 system. The lowest MIC90S (16 micrograms/ml) were observed with ceftriaxone and rifampin. The next lowest MIC90S were found with cephapirin, tetracycline, and chloramphenicol (3.12 micrograms/ml). The MIC90S of penicillin, ampicillin, ticarcillin, piperacillin, and amikacin were each greater than or equal to 12.5 micrograms/ml. Antibiotic synergy was studied by the killing curve method and was defined as a greater than or equal to 2 log10 reduction in CFU when two antibiotics were used in combination at one-fourth the MBC for each compared with the effect of each antibiotic alone at one-half the MBC. Synergism between rifampin and penicillin, cephapirin, or ceftriaxone was tested for with 12 A. actinomycetemcomitans strains. In 7 of 37 instances, synergism was demonstrated for the combinations rifampin plus ceftriaxone (n = 3) or rifampin plus penicillin (n = 4); in 9 instances, an additive effect was noted, and impaired killing with drug combinations compared with the effect of a single antibiotic was suggested in 4 strains. The majority of strains were indifferent to the combinations. Similarly, variable results were observed when the combination of trimethoprim and cephapirin was tested against eight A. actinomycetemcomitans strains. Our data suggest that rifampin and cephapirin are the most active of the 11 antibiotics studied against A. actinomycetemcomitans. In addition, in vitro synergism between rifampin and other antibiotics or between trimethoprim and cephapirin was not consistently demonstrable.

  5. ENZYMATIC ACTIVITY AND ANTIBIOTIC RESISTANCE PROFILE OF LACTOBACILLUS PARACASEI SSP. PARACASEI-1 ISOLATED FROM REGIONAL YOGURTS OF BANGLADESH

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    Ummay Honi

    2013-12-01

    Full Text Available Lactobacillus paracasei ssp. paracasei-1 was identified from traditional yogurts of Khulna region, Bangladesh and its enzyme and antibiotic resistance profiles were determined. A commercially available API Zym kit was employed to determine the activities of 19 different enzymes. We found that L. paracasei ssp. paracasei-1 showed strong activities for several enzymes, viz. leucine arylamidase, valine arylamidase, napthol-AS-BI-phosphohydrolase, β-galactosidase, α –Glucosidase, N-Acetyl- β- glucosaminidase while activities for other enzymes were absent. Antibiotic resistance profile was assessed by minimum inhibitory concentration (MIC test for 61 major antibiotics and 4 antifungal agents obtained from commercial sources in MRS Agar media. The strain generally showed resistance to gram negative spectrum antibiotic while it showed susceptibility towards β-lactam antibiotic to gram positive spectrum antibiotic. The findings provide the therapeutic basis of using L. paracasei ssp. paracasei-1 in finished food products.

  6. The molecular clock: a focus on chronopharmacological strategies for a possible control of aminoglycoside renal toxicity

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    Rebuelto M

    2012-01-01

    Full Text Available Marcela RebueltoFarmacología, Facultad de Ciencias Veterinarias, Universidad de Buenos Aires, Buenos Aires, ArgentinaAbstract: Chronotherapy applies biological rhythmicity in order to optimize clinical treatments, relating the dosing time of the drugs to the daily variations of their therapeutic and unwanted side effects due to the fluctuations in physiological processes involved in their pharmacokinetics and/or pharmacodynamics. The goal of chronotherapy is to administer treatments at the time of day that enhances both their effectiveness and tolerance. This review intends to (1 provide the theoretical rationale behind the use of aminoglycosides during extended interval schedule chronotherapy in clinical practice and (2 target the underlying molecular mechanisms of renal toxicity, the main unwanted side effect. Previous reports suggest that aminoglycoside therapy may benefit from a chronopharmacological approach. Temporal variations in the renal blood flow and glomerular filtration rate and several clock-dependent molecular mechanisms contributing to the daily changes in electrolyte and water urinary excretion have been reported. Daily differences in aminoglycoside toxicity and kinetic disposition have been found in laboratory animals and human patients. Nephrotoxicity and renal cortical accumulation are higher when drugs are administered during the rest phase than during the active phase. Active translocation of aminoglycosides into renal cells is mediated by the megalin/cubilin receptor complex located at the luminal epithelial cell membrane. The complex regulation of this endocytic mechanism deserves further study, in order to dilucidate the molecular bases that may be involved in chronotherapeutic strategies developed for minimizing aminoglycoside accumulation in the renal cells, and thus, increasing their tolerance.Keywords: biological rhythms, chronopharmacology, chronotherapeutics, aminoglycosides

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

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    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.

  8. Production of peptide antifungal antibiotic and biocontrol activity of Bacillus subtilis.

    Science.gov (United States)

    Kumar, Ajay; Saini, Pragati; Shrivastava, J N

    2009-01-01

    Among different bacterial cultures, a potent Bacillus subtilis MTCC-8114 was isolated from garden soil samples which showed 16 and 14 mm inhibition zones by spot inoculation method and 24 and 22 mm inhibition zones by well agar diffusion method against test fungi i.e. Microsporum fulvum and Trichophyton species. Among four media tested, the maximum growth and antibiotic production was found in trypticase soya broth (TSB) medium at 37 degrees C, pH-7 and 48 h of incubation. The Rf value (0.64) by Thin Layer Chromatography (TLC) technique and UV and FTIR spectral data of the active antifungal compound, indicated that the isolated compound belongs to peptide antifungal antibiotic group. MIC value of antifungal antibiotic was 135 and 145 microg/ml.

  9. Mechanisms of antibiotic resistance of Enterobacteriaceae family representatives

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    K. R. Kotsyuba

    2014-04-01

    Full Text Available The paper deals with the basic medical scheme of antibiotics use for treatment of lesions caused by enterobacteria and mechanisms of resistance of Enterobacteriaceae to different classes of antibiotics. It is known that the main mechanisms of resistance to antibiotics are enzymatic inactivation, modification of the target, efflux, violation of conduct through the membrane and formation of metabolic shunt. The most common cases of resistance to beta-lactams among Enterobacteriaceae relate to production of plasmid and chromosomal beta-lactamases, violation of the permeability of the outer membrane, and modification of target penicillin binding proteins. Active release of antibiotics from the cell, or efflux, in Enterobacteriaceae is used for maintaining resistance to tetracyclines, macrolides, carbapenems. Genes of efflux system are localized on plasmids and contribute to rapid spreading among Enterobacteriaceae. Mutations are the basis of resistance to novobiocinum and rifampicinum. Enzymatic inactivation by modifying is typical for resistance to aminoglycosides. Three groups of enzymes are engaged in the process, by adding the molecule of acetic acid, phosphate or adenine. Joining of these groups is irreversible and leads to complete loss of biological activity of the antibiotic. Resistance to aminoglycosides appears also due to inhibition of drug penetration, that is associated with genetically determined mechanisms of electron transport through the membrane. Resistance to quinolones and fluoroquinolones is associated with the modification of topoisomerase II and IV which are targets of these groups of antibiotics. Resistance is possible as a result of changes in the structure of the target, breaching of penetration into the cell, and active release from the cell. The highest level of resistance is develope in the case of two- or three-stage mutations in one or the other, or both, subunits in different genes. At the same time, for breaching of

  10. Evaluation of Antibiotics Active against Methicillin-Resistant Staphylococcus aureus Based on Activity in an Established Biofilm.

    Science.gov (United States)

    Meeker, Daniel G; Beenken, Karen E; Mills, Weston B; Loughran, Allister J; Spencer, Horace J; Lynn, William B; Smeltzer, Mark S

    2016-10-01

    We used in vitro and in vivo models of catheter-associated biofilm formation to compare the relative activity of antibiotics effective against methicillin-resistant Staphylococcus aureus (MRSA) in the specific context of an established biofilm. The results demonstrated that, under in vitro conditions, daptomycin and ceftaroline exhibited comparable activity relative to each other and greater activity than vancomycin, telavancin, oritavancin, dalbavancin, or tigecycline. This was true when assessed using established biofilms formed by the USA300 methicillin-resistant strain LAC and the USA200 methicillin-sensitive strain UAMS-1. Oxacillin exhibited greater activity against UAMS-1 than LAC, as would be expected, since LAC is an MRSA strain. However, the activity of oxacillin was less than that of daptomycin and ceftaroline even against UAMS-1. Among the lipoglycopeptides, telavancin exhibited the greatest overall activity. Specifically, telavancin exhibited greater activity than oritavancin or dalbavancin when tested against biofilms formed by LAC and was the only lipoglycopeptide capable of reducing the number of viable bacteria below the limit of detection. With biofilms formed by UAMS-1, telavancin and dalbavancin exhibited comparable activity relative to each other and greater activity than oritavancin. Importantly, ceftaroline was the only antibiotic that exhibited greater activity than vancomycin when tested in vivo in a murine model of catheter-associated biofilm formation. These results emphasize the need to consider antibiotics other than vancomycin, most notably, ceftaroline, for the treatment of biofilm-associated S. aureus infections, including by the matrix-based antibiotic delivery methods often employed for local antibiotic delivery in the treatment of these infections.

  11. An in vitro study on the effects of nisin on the antibacterial activities of 18 antibiotics against Enterococcus faecalis.

    Science.gov (United States)

    Tong, Zhongchun; Zhang, Yuejiao; Ling, Junqi; Ma, Jinglei; Huang, Lijia; Zhang, Luodan

    2014-01-01

    Enterococcus faecalis rank among the leading causes of nosocomial infections worldwide and possesses both intrinsic and acquired resistance to a variety of antibiotics. Development of new antibiotics is limited, and pathogens continually generate new antibiotic resistance. Many researchers aim to identify strategies to effectively kill this drug-resistant pathogen. Here, we evaluated the effect of the antimicrobial peptide nisin on the antibacterial activities of 18 antibiotics against E. faecalis. The MIC and MBC results showed that the antibacterial activities of 18 antibiotics against E. faecalis OG1RF, ATCC 29212, and strain E were significantly improved in the presence of 200 U/ml nisin. Statistically significant differences were observed between the results with and without 200 U/ml nisin at the same concentrations of penicillin or chloramphenicol (pnisin and penicillin or chloramphenicol had a synergetic effect against the three tested E. faecalis strains. The transmission electron microscope images showed that E. faecalis was not obviously destroyed by penicillin or chloramphenicol alone but was severely disrupted by either antibiotic in combination with nisin. Furthermore, assessing biofilms by a confocal laser scanning microscope showed that penicillin, ciprofloxacin, and chloramphenicol all showed stronger antibiofilm actions in combination with nisin than when these antibiotics were administered alone. Therefore, nisin can significantly improve the antibacterial and antibiofilm activities of many antibiotics, and certain antibiotics in combination with nisin have considerable potential for use as inhibitors of this drug-resistant pathogen.

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

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    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].

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

    Science.gov (United States)

    Oh, Euna; Jeon, Byeonghwa

    2015-01-01

    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.

  14. 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.

  15. 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.

  16. 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. PMID:27547203

  17. Identification of genes involved in low aminoglycoside-induced SOS response in Vibrio cholerae: a role for transcription stalling and Mfd helicase.

    Science.gov (United States)

    Baharoglu, Zeynep; Babosan, Anamaria; Mazel, Didier

    2014-02-01

    Sub-inhibitory concentrations (sub-MIC) of antibiotics play a very important role in selection and development of resistances. Unlike Escherichia coli, Vibrio cholerae induces its SOS response in presence of sub-MIC aminoglycosides. A role for oxidized guanine residues was observed, but the mechanisms of this induction remained unclear. To select for V. cholerae mutants that do not induce low aminoglycoside-mediated SOS induction, we developed a genetic screen that renders induction of SOS lethal. We identified genes involved in this pathway using two strategies, inactivation by transposition and gene overexpression. Interestingly, we obtained mutants inactivated for the expression of proteins known to destabilize the RNA polymerase complex. Reconstruction of the corresponding mutants confirmed their specific involvement in induction of SOS by low aminoglycoside concentrations. We propose that DNA lesions formed on aminoglycoside treatment are repaired through the formation of single-stranded DNA intermediates, inducing SOS. Inactivation of functions that dislodge RNA polymerase leads to prolonged stalling on these lesions, which hampers SOS induction and repair and reduces viability under antibiotic stress. The importance of these mechanisms is illustrated by a reduction of aminoglycoside sub-MIC. Our results point to a central role for transcription blocking at DNA lesions in SOS induction, so far underestimated.

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

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    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.

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

    Science.gov (United States)

    Bashir, Yasir; Dar, Firdous Ahmad; Sekhar, M.

    2016-01-01

    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. PMID:27403451

  20. 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.

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

    Science.gov (United States)

    Karah, Nabil; Dwibedi, Chinmay Kumar; Sjöström, Karin; Edquist, Petra; Johansson, Anders; Wai, Sun Nyunt; Uhlin, Bernt Eric

    2016-01-11

    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.

  2. 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.

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

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    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.

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

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    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.

  5. 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

    , expression of all three genes were repressed by aminoglycosides and induced by fluoroquinolones and penicillins. In contrast, the beta-lactam sub-group cephalosporins enhanced expression of RNAIII and hla but diversely affected expression of spa. The compounds cefalotin, cefamandole, cefoxitin, ceftazidime...

  6. Forgotten antibiotics

    DEFF Research Database (Denmark)

    Pulcini, Céline; Bush, Karen; Craig, William A

    2012-01-01

    disease specialists in Europe, the United States, Canada, and Australia. An international expert panel selected systemic antibacterial drugs for their potential to treat infections caused by resistant bacteria or their unique value for specific criteria. Twenty-two of the 33 selected antibiotics were...... available in fewer than 20 of 38 countries. Economic motives were the major cause for discontinuation of marketing of these antibiotics. Fourteen of 33 antibiotics are potentially active against either resistant Gram-positive or Gram-negative bacteria. Urgent measures are then needed to ensure better...

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

    OpenAIRE

    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 poss...

  8. Synthesis and biological activity of new quinoxaline antibiotics of echinomycin analogues.

    Science.gov (United States)

    Kim, Yun Bong; Kim, Yong Hae; Park, Ju Youn; Kim, Soo Kie

    2004-01-19

    Novel quinoxaline antibiotics having the methylenedithioether bridge as an analogue of echinomycin have been synthesized by insertion of methylene moiety between -S-S- bond. The compound 1a shows remarkable cytotoxicities against human tumor various cell lines, and is active VRE (vancomycin-resistant enterococci) within MIC range 0.5-8 microg/mL. According to the eukaryotic or prokaryotic data, 1a might be a first analogue to replace echinomycin.

  9. Biochemical studies on the Natamycin antibiotic produced by Streptomyces lydicus: Fermentation, extraction and biological activities

    OpenAIRE

    Atta, H.M.; A.S. El-Sayed; M.A. El-Desoukey; Hassan, M.; M. El-Gazar

    2015-01-01

    Natamycin “polyene” antibiotic was isolated from the fermentation broth of a Streptomyces strain No. AZ-55. According to the morphological, cultural, physiological and biochemical characteristics, and 16S rDNA sequence analysis, strain AZ-55 was identified as Streptomyces lydicus. It is active in vitro against some microbial pathogens viz: Staphylococcus aureus, NCTC 7447; Bacillus subtilis, NCTC 1040; Bacillus pumilus, NCTC 8214 ; Micrococcus luteus, ATCC 9341; Escherichia coli, NCTC 10416; ...

  10. Investigations into the Antibacterial Activity of the Silver-Based Antibiotic Drug Candidate SBC3

    Directory of Open Access Journals (Sweden)

    Matthias Tacke

    2012-11-01

    Full Text Available The synthesis of N-heterocyclic carbene (NHC silver(I acetate complexes with varying lipophilic benzyl-substituents at the 1 and 3 positions starting from 4,5-diphenylimidazole, opened a new class of antibiotic drug candidates. These NHC-silver(I acetate derivatives exhibit interesting structural motifs in the solid state and proved to be soluble and stable in biological media. The leading candidate, SBC3, which was known to exhibit good antibacterial activity in preliminary Kirby-Bauer tests, was tested quantitatively using minimum inhibitory concentrations. NHC-silver(I acetate complexes were found to have MIC values ranging from 20 to 3.13 μg/mL for a variety of Gram-positive, Gram-negative and mycobacteria tested. These values represent good antibiotic activities against potential pathogens when compared to clinically approved antibiotics. Most striking is the fact that SBC3 is active against methicillin-resistant Staphylococcus aureus with a MIC value of 12.5 μg/mL.

  11. Screening of Actinomycete Isolates from Niche Habitats in Manipur for Antibiotic Activity

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    Debananda S. Ningthoujam

    2009-01-01

    Full Text Available Problem statement: The exhaustion of the usual terrestrial sources and the rise of resistant pathogens dictate the search for novel actinomycetes and new antibiotics. In this context, niche habitats such as caves, pristine forests, lakes, rivers, and other wetlands, high salt environments, marine ecosystems and endophytic niches are promising targets for survey of bioactive actinomycetes. Approach: Actinomycetes were isolated from several niche habitats in Manipur, India, on selective media such as SCNA and Chitin agar with or without antibiotics. Selected isolates were subjected to antimicrobial activity screening by Kirby-Bauer method. Results: 172 lake sediment (SCNA, LS1 series, 35 lake sediment (CA, LSCH series, 120 river (NRP, NRB and..series, 39 forest (AML series, 35 cave (KC1 series, 101 salt spring (NH, N3S and .. series, 46 Shirui jungle (SJ series and 66 Shirui hill (SH series actinomycetes isolates were obtained. Of 99 randomly selected isolates screened, 37 had antimicrobial activities against 1 or more indicator strains: 32 against Gram positive bacteria and 8 against Gram negative bacteria; 10 actinomycete strains were antimycotic and 3 had broad-spectrum antibiotic activities. About 18 potent antibacterial, 1 anti pseudomonas, 1 exclusively antifungal and 3 broad-spectrum antimicrobial actinomycetes were chosen for further studies. Conclusion: Niche habitats in Manipur especially wetlands show great promise for discovery of bioactive actinomycetes.

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

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    K. Stefan Svahn

    2012-05-01

    Full Text Available 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.

  13. Biochemical studies on the Natamycin antibiotic produced by Streptomyces lydicus: Fermentation, extraction and biological activities

    Directory of Open Access Journals (Sweden)

    H.M. Atta

    2015-07-01

    Full Text Available Natamycin “polyene” antibiotic was isolated from the fermentation broth of a Streptomyces strain No. AZ-55. According to the morphological, cultural, physiological and biochemical characteristics, and 16S rDNA sequence analysis, strain AZ-55 was identified as Streptomyces lydicus. It is active in vitro against some microbial pathogens viz: Staphylococcus aureus, NCTC 7447; Bacillus subtilis, NCTC 1040; Bacillus pumilus, NCTC 8214 ; Micrococcus luteus, ATCC 9341; Escherichia coli, NCTC 10416; Klebsiella pneumonia, NCIMB 9111; Salmonella typhi and Pseudomonas aeruginosa, ATCC 10145; S. cerevisiae, ATCC 9763; Candida albicans, IMRU 3669; Aspergillus flavus, IMI 111023; Aspergillus niger, IMI 31276; Aspergillus fumigatus, ATCC 16424; Fusarium oxysporum; Alternaria alternata and Rhizoctonia solani. The active metabolite was extracted using chloroform (1:1, v/v at pH 7.0. The separation of the active ingredient of the antifungal agent and its purification were performed using both thin layer chromatography (TLC and column chromatography (CC techniques. The physico-chemical characteristics of the purified antibiotic viz. color, melting point, solubility, elemental analysis (C, H, N, O and S and spectroscopic characteristics (UV absorbance and IR, mass & NMR spectra have been investigated. This analysis indicates a suggested empirical formula of C33H47NO13. The chemical structural analysis with spectroscopic characteristics confirmed that the compound produced by S. lydicus, AZ-55 is Natamycin “polyene” antibiotic.

  14. 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.

  15. Activity and interactions of antibiotic and phytochemical combinations against Pseudomonas aeruginosa in vitro

    Directory of Open Access Journals (Sweden)

    Premkumar Jayaraman, Meena K Sakharkar, Chu Sing Lim, Thean Hock Tang, Kishore R. Sakharkar

    2010-01-01

    Full Text Available In this study the in vitro activities of seven antibiotics (ciprofloxacin, ceftazidime, tetracycline, trimethoprim, sulfamethoxazole, polymyxin B and piperacillin and six phytochemicals (protocatechuic acid, gallic acid, ellagic acid, rutin, berberine and myricetin against five P. aeruginosa isolates, alone and in combination are evaluated. All the phytochemicals under investigation demonstrate potential inhibitory activity against P. aeruginosa. The combinations of sulfamethoxazole plus protocatechuic acid, sulfamethoxazole plus ellagic acid, sulfamethoxazole plus gallic acid and tetracycline plus gallic acid show synergistic mode of interaction. However, the combinations of sulfamethoxazole plus myricetin shows synergism for three strains (PA01, DB5218 and DR3062. The synergistic combinations are further evaluated for their bactericidal activity against P. aeruginosa ATCC strain using time-kill method. Sub-inhibitory dose responses of antibiotics and phytochemicals individually and in combination are presented along with their interaction network to suggest on the mechanism of action and potential targets for the phytochemicals under investigation. The identified synergistic combinations can be of potent therapeutic value against P. aeruginosa infections. These findings have potential implications in delaying the development of resistance as the antibacterial effect is achieved with lower concentrations of both drugs (antibiotics and phytochemicals.

  16. Degradation of antibiotic activity during UV/H2O2 advanced oxidation and photolysis in wastewater effluent.

    Science.gov (United States)

    Keen, Olya S; Linden, Karl G

    2013-11-19

    Trace levels of antibiotics in treated wastewater effluents may present a human health risk due to the rise of antibacterial activity in the downstream environments. Advanced oxidation has a potential to become an effective treatment technology for transforming trace antibiotics in wastewater effluents, but residual or newly generated antibacterial properties of transformation products are a concern. This study demonstrates the effect of UV photolysis and UV/H2O2 advanced oxidation on transformation of 6 antibiotics, each a representative of a different structural class, in pure water and in two different effluents and reports new or confirmatory photolysis quantum yields and hydroxyl radical rate constants. The decay of the parent compound was monitored with HPLC/ITMS, and the corresponding changes in antibacterial activity were measured using bacterial inhibition assays. No antibacterially active products were observed following treatment for four of the six antibiotics (clindamycin, ciprofloxacin, penicillin-G, and trimethoprim). The remaining two antibiotics (erythromycin and doxycycline) showed some intermediates with antibacterial activity at low treatment doses. The antibacterially active products lost activity as the UV dose increased past 500 mJ/cm(2). Active products were observed only in wastewater effluents and not in pure water, suggesting that complex secondary reactions controlled by the composition of the matrix were responsible for their formation. This outcome emphasizes the importance of bench-scale experiments in realistic water matrices. Most importantly, the results indicate that photosensitized processes during high dose wastewater disinfection may be creating antibacterially active transformation products from some common antibiotics.

  17. Incidence and antibiotic susceptibility of genital mycoplasmas in sexually active individuals in Hungary.

    Science.gov (United States)

    Pónyai, K; Mihalik, N; Ostorházi, E; Farkas, B; Párducz, L; Marschalkó, M; Kárpáti, S; Rozgonyi, F

    2013-11-01

    The aim of this study was to examine the incidence and antibiotic sensitivity of Ureaplasma urealyticum and Mycoplasma hominis strains cultured from the genital discharges of sexually active individuals who attended our STD outpatient service. Samples were taken with universal swab (Biolab®, Budapest, Hungary) into the Urea-Myco DUO kit (Bio-Rad®, Budapest, Hungary) and incubated in ambient air for 48 h at 37 °C. The determination of antibiotic sensitivity was performed in U9 and arginin broth using the SIR Mycoplasma kit (Bio-Rad®, Budapest, Hungary) under the same conditions. Between 01.05.2008 and 31.12.2011, 373/4,466 (8.35 %) genito-urethral samples with U. urealyticum and 41/4,466 (0.91 %) genito-urethral samples with M. hominis infection were diagnosed in sexually active individuals in the National STD Center, Semmelweis University. U. urealyticum was isolated in 12.54 % in the cervix and 4.1 % in the male urethra, while M. hominis was isolated in 1.33 % in the cervix and 0.51 % in the male urethra. The affected age group was between 21 and 60 years old. U. urealyticum strains were sensitive to tetracycline (95.9 %), doxycycline (97.32 %), and azithromycin (85.79 %), and resistant to erythromycin (81.23 %), clindamycin (75.06 %), and ofloxacin (25.2 %). Cross-resistance occurred in 38.71 % of patients to erythromycin and clindamycin. M. hominis strains were sensitive to clindamycin, ofloxacin, and doxycycline in more than 95 %, to tetracycline in 82.92 %, and no cross-resistance was detected among the antibiotics. Our study confirms that the continuously changing antibiotic resistance of ureaplasmas and mycoplasmas should be followed at least in a few centers in every country, so as to determine the best local therapy options for sexually transmitted infection (STI) patients.

  18. Antimicrobial peptides from arachnid venoms and their microbicidal activity in the presence of commercial antibiotics.

    Science.gov (United States)

    Garcia, Francia; Villegas, Elba; Espino-Solis, Gerardo Pavel; Rodriguez, Alexis; Paniagua-Solis, Jorge F; Sandoval-Lopez, Gabriel; Possani, Lourival D; Corzo, Gerardo

    2013-01-01

    Two antimicrobial peptides (AMPs), named La47 and Css54, were isolated from the venom of the spider Lachesana sp. and from the scorpion Centruroides suffusus suffusus, respectively. The primary structures of both La47 and Css54 were determined using N-terminal sequencing and mass spectrometry. La47 is identical to the AMP latarcin 3a obtained previously from the venom of the spider Lachesana tarabaevi, but the primary structure of Css54 is unique having 60% identities to the AMP ponericin-W2 from the venom of the ant Pachycondyla goeldii. Both La47 and Css54 have typical α-helix secondary structures in hydrophobic mimicking environments. The biological activities of both La47 and Css54 were compared with the AMP Pin2 isolated from the venom of the scorpion Pandinus imperator. La47 has lower antimicrobial and hemolytic activities compared with Css54 and Pin2. In addition, La47 and Pin2 were evaluated in the presence of the commercial antibiotics, chloramphenicol, ampicillin, novobiocin, streptomycin and kanamycin. Interestingly, the best antimicrobial combinations were obtained with mixtures of La47 and Pin2 with the antibiotics chloramphenicol, streptomycin and kanamycin, respectively. Furthermore, the novel peptide Css54 was evaluated in the presence of antibiotics used for the treatment of tuberculosis, isoniazid, rifampicin, pyrazinamide and ethambutol. Although the mixtures of Css54 with isoniazid, pyrazinamide or ethambutol inhibit the growth of Staphylococcus aureus, the best effect was found with rifampicin. Overall, these data show a motivating outlook for potential clinical treatments of bacterial infections using AMPs and commercial antibiotics.

  19. New options of antibiotic combination therapy for multidrug-resistant Pseudomonas aeruginosa.

    Science.gov (United States)

    Nakamura, I; Yamaguchi, T; Tsukimori, A; Sato, A; Fukushima, S; Matsumoto, T

    2015-01-01

    Several antibiotic combinations have demonstrated increased activity against multidrug-resistant Pseudomonas aeruginosa (MDRP) in vitro compared with a single antibiotic. The aim of this study was to investigate the activity against MDRP of some aminoglycosides in combination with monobactam, piperacillin (PIPC), and carbapenem. Clinical isolates of MDRP were collected between November 2010 and October 2012 from patients in Tokyo Medical University Hospital, Tokyo (1,015 beds). Our new method was designed to evaluate three concentrations around the breakpoint of each drug using the Checkerboard method. The aminoglycosides tested were amikacin (AMK), tobramycin (TOB), and arbekacin (ABK). Ciprofloxacin, PIPC, and biapenem (BIPM), which have been reported to demonstrate combination effects, were also tested. Sixty-six MDRP strains were identified from the 2,417 P. aeruginosa strains. Of the 66, 27 tested positive for metallo-β-lactamase (MBL). Aztreonam (AZT) with AMK or ABK was the most effective against MDRP. PIPC with AMK or ABK were somewhat effective. AZT with AMK or ABK were more effective against MBL-positive strains than MBL-negative strains. However, PIPC with AMK or ABK were more effective against MBL-negative strains than MBL-positive strains. Combination activities showed differences between MBL-positive and MBL-negative strains.

  20. Host defence peptides: antimicrobial and immunomodulatory activity and potential applications for tackling antibiotic-resistant infections

    Directory of Open Access Journals (Sweden)

    2009-01-01

    Full Text Available

    The rapidly increasing incidence of multidrug-resistant infections and the alarmingly low rate of discovery of conventional antibiotics create an urgent need for alternative strategies to treat bacterial infections. Host defence peptides are short cationic molecules produced by the immune systems of most multicellular organisms; they are a class of compounds being actively researched. In this review, we provide an overview of the antimicrobial and immunomodulatory activities of natural host defence peptides, and discuss strategies for creating artificial derivatives with improved biological and pharmacological properties, issues of microbial resistance, and challenges associated with their adaptation for clinical use.

  1. Sustainable Activated Carbons from Agricultural Residues Dedicated to Antibiotic Removal by Adsorption

    Institute of Scientific and Technical Information of China (English)

    Jonatan Torres-Perez; Claire Gerente; Yves Andres

    2012-01-01

    The. objectives.of this study are to convert at laboratory s.cale agric.ultural residues into activated carbons (AC) with specific properties, to characterize them and to test them in adsorption reactor for tetracycline removal, a common antibiotic. Two new ACs were produced by direct activation with steam from beet pulp (BP-H2O) and peanut hu_lls (PH-H2O) in environmental friendly conditions BP-H2O and PH-H2Opresentcarbon content rangedcarbons with different intrinsic properties.

  2. Melaleuca alternifolia essential oil possesses potent anti-staphylococcal activity extended to strains resistant to antibiotics.

    Science.gov (United States)

    Ferrini, A M; Mannoni, V; Aureli, P; Salvatore, G; Piccirilli, E; Ceddia, T; Pontieri, E; Sessa, R; Oliva, B

    2006-01-01

    Melaleuca alternifolia Cheel essential oil (TTO) and its major component terpinen-4-ol were examined against a large number of clinical isolates of Staphylococcus aureus to establish their anti-staphylococcal activities. Classic and established procedures were used to study M.I.C., time-kill curves, synergism and mutational frequency. The anti-staphylococcal activity of terpinen-4-ol and TTO were superior to those of antibiotics belonging to the major families (all the tested drugs are for topical use or included in ointments, eye drops or used during surgery); terpinen 4-ol and TTO were active against strains resistant to mupirocin, fusidic acid, vancomycin, methicillin and linezolid. TTO and terpinen-4-ol were bactericidal as revealed by time-kill curves; the frequency of mutational frequency to TTO was < 2.9 x 10 9. The study demonstrates good anti-staphylococcal activity of TTO and terpinen-4-ol against a large number of S.aureus isolates and suggests the possible application of these agents for topical treatment of staphylococcal infections. This is the first extensive study on the anti-staphylococcal activity of TTO. The results suggest that this compound may have application as a topical agent for the control of superficial staphylococcal infections, including activity against organisms resistant to antibiotics which can be used, or are specific, for topical use.

  3. Extended-Interval Dosing of Aminoglycosides in Pediatrics: A Narrative Review

    Directory of Open Access Journals (Sweden)

    Ebrahim Salehifar

    2015-07-01

    Full Text Available Aminoglycosides (AGs are frequently used in pediatric settings, especially for empiric treatment of early-onset neonatal sepsis. Although AGs are used for several decades, the optimum method of administration and their dosing schemes needs more clarification. The risks of ototoxicity and nephrotoxicity, two main toxicities associated with AGs, have been contributed to the peak and trough plasma levels, respectively. One approach to decrease these potential toxicities of AGs is to administer higher doses with a prolonged interval, named extended-interval dosing (EID. Post-antibiotic effect (PAE and concentration-dependent killing of AGs provide rational basis for the efficacy of EID. PAE refers to the extended bactericidal activity of AGs against many Gram-negative organisms after the drug was removed by metabolism. One concern is that the higher initial peak concentration with EID may be accompanied with more toxicities, especially ototoxicity. It was demonstrated that due to saturation of binding site of AGs in renal and cochlear tissues, transiently higher concentration of AGs does not cause additional nephrotoxicity or ototoxicity. Experience and clinical evidence regarding EID in pediatrics is suboptimal. In this review, we presented the rational and studies focusing on EID in pediatric setting. The overall finding of trials is that in pediatric setting, EID is a safe and effective dosing method. The risk of serum drug concentration outside the therapeutic range is lower in neonates treated with EID, leading to less need of therapeutic drug monitoring (TDM with EID. Moreover, there are evidences supporting lower chance of bacterial resistance with EID compared with traditional dosing approach.

  4. Adsorption of quinolone, tetracycline, and penicillin antibiotics from aqueous solution using activated carbons: Review.

    Science.gov (United States)

    Ahmed, Muthanna J

    2017-03-01

    Antibiotics, an important type of pharmaceutical pollutant, have attracted many researchers to the study of their removal from aqueous solutions. Activated carbon (AC) has been widely used as highly effective adsorbent for antibiotics because of its large specific surface area, high porosity, and favorable pore size distribution. In this article, the adsorption performance of AC towards three major types of antibiotics such as tetracyclines, quinolones, and penicillins were reviewed. According to collected data, maximum adsorption capacities of 1340.8, 638.6, and 570.4mg/g were reported for tetracyclines, quinolones, and penicillins, respectively. The values of 1/n for Freundlich isotherm were less than unity, suggesting that the adsorption was nonlinear and favorable. Adsorption kinetics followed closely the pseudo-second-order model and analysis using the Weber-Morris model revealed that the intra-particle diffusion was not the only rate controlling step. AC adsorption demonstrated superior performance for all selected drugs, thus being efficient technology for treatment of these pollutants.

  5. 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.

  6. Antibiotic susceptibility and antimicrobial activity of autochthonous starter cultures as safety parameters for fresh cheese production

    Directory of Open Access Journals (Sweden)

    Dora Bučan

    2013-11-01

    Full Text Available The antibiotic susceptibility and antimicrobial activity, as food safety parameters important for application of autochthonous lactic acid bacteria (LAB, that previously satisfied technological criteria for functional starter cultures in fresh cheese production were examined. Soluble whole cell protein patterns of autochthonous LAB strains from fresh cheese, obtained by SDS-PAGE, revealed the presence of two predominant strains, which were identified as Lactobacillus fermentum A8 and Enterococcus faecium A7. These strains were not resistant and shown susceptibility to antibiotics: ampicillin, bacitracin, penicillin G, azithromycin, chloramphenicol, clarithromycin, clindamycin, spiramycin, tetracycline, streptomycin, neomycin, gentamicin, erythromycin, rifampicin and novobiocin. Lb. fermentum A8 strain displayed phenotypic resistance to vancomycin, but this resistance is intrinsic, not transferable and it is acceptable from the safety aspect. The capacity of Lb. fermentum A8 and Ec. faecium A7 to inhibit growth of test-microorganisms Listeria monocytogenes ATCC 11911, Escherichia coli 3014, Salmonella enterica serovar Typhimurium FP1 and Staphylococcus aureus 3048, was also analysed. According to obtained results, Lb. fermentum A8 and Ec. faecium A7 are safe from the aspect of spreading antibiotic resistance and could be useful as bioprotective cultures that inhibit common bacterial food contaminants, including L. monocytogenes.

  7. On the use of antibiotics to reduce rhizoplane microbial populations in root physiology and ecology investigations

    Science.gov (United States)

    Smart, D. R.; Ferro, A.; Ritchie, K.; Bugbee, B. G.

    1995-01-01

    No straightforward method exists for separating the proportion of ion exchange and respiration due to rhizoplane microbial organisms from that of root ion exchange and respiration. We examined several antibiotics that might be used for the temporary elimination of rhizoplane bacteria from hydroponically grown wheat roots (Triticum aestivum cv. Veery 10). Each antibiotic was tested for herbicidal activity and plate counts were used to enumerate bacteria and evaluate antibiotic kinetics. Only lactam antibiotics (penicillins and cephalosporins) did not reduce wheat growth rates. Aminoglycosides, the pyrimidine trimethoprim, colistin and rifampicin reduced growth rates substantially. Antibiotics acted slowly, with maximum reductions in rhizoplane bacteria occurring after more than 48 h of exposure. Combinations of nonphytotoxic antibiotics reduced platable rhizoplane bacteria by as much as 98%; however, this was generally a reduction from about 10(9) to 10(6) colony forming units per gram of dry root mass, so that many viable bacteria remained on root surfaces. We present evidence which suggests that insufficient bacterial biomass exists on root surfaces of nonstressed plants grown under well-aerated conditions to quantitatively interfere with root nitrogen absorption measurements.

  8. Screening a Mediterranean Sponge Axinella verrucosa For Antibacterial Activity in Comparison to Some Antibiotics

    Directory of Open Access Journals (Sweden)

    Alma Shabbar

    2013-03-01

    Full Text Available The antibacterial effect of crude extract of marine sponge Axinella verrucosa at room temperature against seven nosocomial bacteria and one fungal isolates including, Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter septicus and Proteus vulgaris, Acinetobacter meningitis, Klebsiella pneumonia, E. coli and the fungal pathogen Candida albicans were studied by Kirby-Bauer disc diffusion assay and, the findings of antibacterial activity of crude methanolic extract sponge A. verrucosa were compared to the efficiency of some marketed antibiotics that were tested against the same bacteria at given concentrations. In result, it was found that MeOH crude extract of Axinella verrucosa is effective against Staphylococcus aureus, Pseudomonas aeruginosa, Acinetobacter septicus and Proteus vulgaris and except for its ineffectiveness against Acinetobacter meningitis, Klebsiella pneumonia, E. coli and the fungal pathogen Candida albicans. It was more active than Azithromycin and Gentamicin Against Proteus vulgaris and more efficient than ciprofloxacin against Acinetobacter septicus. Hexane and Ethyl acetate crude extracts derived from A. verrucosa revealed no activity against all bacterial and fungal pathogen. Sponge Axinella verrucosa remains an interesting source of new antibacterial metabolites with better activity than some antibiotics.

  9. ANTIBACTERIAL ACTIVITY OF TRADITIONAL HERBS AND STANDARD ANTIBIOTICS AGAINST POULTRY ASSOCIATED PSEUDOMONAS AERUGINOSA

    Directory of Open Access Journals (Sweden)

    Affia Rafique

    2012-10-01

    Full Text Available Present study aims to access the antibacterial activity of medicinal plants and antibiotics against poultry associated Pseudomonas aeruginosa. P. aeruginosa is the most widespread avian pathogen and it produces a range of toxins and enzymes that may contribute to pathogenicity. P. aeruginosa was isolated from the chicken liver and identified through biochemical methods. The antibacterial activity of extracts of medicinal herbs and various antibiotics were analyzed against P. aeruginosa through agar disc diffusion method. P. aeruginosa was susceptible against Norfloxacin, Chloramphenicol, Streptomycin, Gentamicin, Tobramycin, and Ciprofloxacin. Whereas, moderately susceptible in case of Oxytetracycline, Neomycin, Lincomycin, and Sulfomethoxyzol. It was also analyzed that Ampicillin, Tetracycline, Penicillin G and Trimethoprim had no effect. Among the plants tested C. zylanicum, C. cyminum, T. ammi, S. aromaticum and green part of M. charantia were most active. The maximum antibacterial activity was calculated by the extracts of isoamylalcohol of C. zylanicum, C. cyminum, T. ammi, S. aromaticum, and ethanolic and methanol extract of green part of M. charantia against P. aeruginosa. This study indicated that these medicinal plants could be the potential source for antimicrobial agents. Hence, these medicinal plants can be further subjected to isolation of the therapeutic antimicrobials and further pharmacological evaluation.

  10. Isolation, purification and identification of three peptaibols from Trichoderma koningii with antibiotic activity against Ralstonia solancearum

    Institute of Scientific and Technical Information of China (English)

    SHEN Qing-tao; CHEN Xiu-lan; SUN Cai-yun; ZHANG Yu-zhong

    2004-01-01

    @@ The use of microorganisms for biological purposes has become an effective alternative to control plant pathogens. Trichoderma koningii Smf2 was chosen from eight Trichoderma strains for its thermostatic metabolites with antibiotic activity against Ralstonia solancearum Smith. Exclusion chromatography (LH20) was used twice to partially purify targeted metabolites combined with biological test. LC/ESI-MS, a powerful tool for rapid identification and sequence determination of peptides, identified these metabolites as three peptaibols named Trichokonin Ⅵ, Ⅶ and Ⅷ, and their sequences were confirmed with NMR.

  11. Synthesis and antimicrobial activity of amide derivatives of polyether antibiotic-salinomycin.

    Science.gov (United States)

    Huczyński, Adam; Janczak, Jan; Stefańska, Joanna; Antoszczak, Michał; Brzezinski, Bogumil

    2012-07-15

    For the first time a direct and practical approach to the synthesis of eight amide derivatives of polyether antibiotic-salinomycin is described. The structure of allyl amide (3a) has been determined using X-ray diffraction. Salinomycin and its amide derivatives have been screened for their in vitro antimicrobial activity against the typical gram-positive cocci, gram-negative rods and yeast-like organisms, as well as against a series of clinical isolates of methicillin-resistant Staphylococcus aureus and methicillin-sensitive S. aureus. Amides of salinomycin have been found to show a wide range of activities, from inactive at 256 μg/mL to active with MIC of 2 μg/mL, comparable with salinomycin. As a result, phenyl amide (3b) was found to be the most active salinomycin derivative against gram-positive bacteria, MRSA and MSSA.

  12. Production of polypeptide antibiotic from Streptomyces parvulus and its antibacterial activity

    Directory of Open Access Journals (Sweden)

    Prakasham Reddy Shetty

    2014-01-01

    Full Text Available A highly potent secondary metabolite producing actinomycetes strain is isolated from marine soil sediments of Visakhapatnam sea coast, Bay of Bengal. Over all ten strains are isolated from the collected soil sediments. Among the ten actinomycetes strains the broad spectrum strain RSPSN2 was selected for molecular characterization, antibiotic production and its purification. The nucleotide sequence of the 1 rRNA gene (1261 base pairs of the most potent strain evidenced a 96% similarity with Streptomyces parvulus 1044 strain, Streptomyces parvulus NBRC 13193 and Streptomyces parvulus BY-F. From the taxonomic features, the actinomycetes isolate RSPSN2 matches with Streptomyces parvulus in the morphological, physiological and biochemical characters. Thus, it was given the suggested name Streptomyces parvulus RSPSN2. The active metabolite was extracted using ethyl acetate (1:3, v/v at pH 7.0. The separation of active ingredient and its purification was performed by using both thin layer chromatography (TLC and column chromatography (CC techniques. Spectrometric studies such as UV-visible, FTIR, and NMR and mass were performed. The antibacterial activity of pure compound was performed by cup plate method against some pathogenic bacteria including of streptomycin resistant bacteria like (Pseudomonas mirabilis. Pseudomonas putida and Bacillus cereus. In conclusion, the collected data emphasized the fact that a polypeptide antibiotic (Actinomycin D was produced by Streptomyces parvulus RSPSN2.

  13. [Effect of metalloproteins on the photochemical activity of chloroplasts treated with polyene antibiotics].

    Science.gov (United States)

    Mutuskin, A A; Makovkina, L E; Pshenova, K V; Vostroknutova, G N

    1977-04-01

    The effects of various metall-containing proteins (plastocyanin, plantacyanin, azurine and cytochromes of the f type) on the activity of photosystem I of chloroplasts, treated with polyene antibiotics, were studied. The inhibiting effect of the polyenes, surgumycin and philipin, was completely removed by an addition of copper-containing protein plastocyanin. No similar effect was exerted by other Cu-containing proteins--azurine and plantacyanin. The cytochromes of the f type isolated from the green algae chlorella, blue-green algae spiruline and aphanezomenone, having different electrophoretic properties, restored the activity of photosystem I of chloroplasts incubated with antibiotics in a different degree. Acid cytochrome f of chlorella restored the activity by 80--100%; less acid cytochrome f from spiruline-only by 50%. The least restoring effect was exerted by aphanezomenone cytochrome, which possesses some basic properties. The chloroplasts treatment with surgumycin did not affect the isolation of the terminal enzyme of the chloroplast electron-transporting chain of ferredoxin--NADP--reductase. Possible environment of plastocyanin in the chloroplast membrane and the mechanism of photosystem I restoration are discussed.

  14. Amphibian skin secretions as a new source of antibiotics and biologically active substances

    Directory of Open Access Journals (Sweden)

    Ireneusz Całkosiński

    2009-11-01

    Full Text Available So far, the main sources of biologically active substances used in medicine have been plants, molds, and propolis. The obtained compounds have either therapeutic features or require additional modification. They are sometimes combined with other pharmacological substances to intensify their therapeutic effect. However, the effectiveness of many drugs has been rapidly decreasing. The overuse of antibiotics in the treatment and prophylaxis of human infections (especially in hospitals as well as their widespread and often unjustified use in the treatment and prophylaxis of farm animal illnesses contribute to the development of a variety of resistance mechanisms by microorganisms. Because of the increasing ineffectiveness of antibiotics used so far and difficulties in obtaining new drugs, it is necessary to find new sources of these compounds, for example in animal organisms. Research has demonstrated that amphibian skin secretions are rich in a variety of active substances which have strong pharmacological properties. In these compounds we can distinguish, for example, toxins, antimicrobial peptides, opioid peptides, steroids, and alkaloids. These compounds show cytotoxic, antimicrobial, analgesic, anti-inflammatory, and even antiviral activities (including anti-HIV. These substances can be used in cell receptor studies and in transmembrane ion transport analysis. Because these compounds are secreted by skin glands, they can be easy obtained without injuring these animals. It is probable that amphibian skin constitutes a potential source of modern drugs.

  15. [Amphibian skin secretions as a new source of antibiotics and biologically active substances].

    Science.gov (United States)

    Całkosiński, Ireneusz; Zasadowski, Arkadiusz; Bronowicka-Szydełko, Agnieszka; Dzierzba, Katarzyna; Seweryn, Ewa; Dobrzyński, Maciej; Gamian, Andrzej

    2009-11-12

    So far, the main sources of biologically active substances used in medicine have been plants, molds, and propolis. The obtained compounds have either therapeutic features or require additional modification. They are sometimes combined with other pharmacological substances to intensify their therapeutic effect. However, the effectiveness of many drugs has been rapidly decreasing.The overuse of antibiotics in the treatment and prophylaxis of human infections (especially in hospitals) as well as their widespread and often unjustified use in the treatment and prophylaxis of farm animal illnesses contribute to the development of a variety of resistance mechanisms by microorganisms. Because of the increasing ineffectiveness of antibiotics used so far and difficulties in obtaining new drugs, it is necessary to find new sources of these compounds, for example in animal organisms. Research has demonstrated that amphibian skin secretions are rich in a variety of active substances which have strong pharmacological properties. In these compounds we can distinguish, for example, toxins, antimicrobial peptides, opioid peptides, steroids, and alkaloids.These compounds show cytotoxic, antimicrobial, analgesic, anti-inflammatory, and even antiviral activities (including anti-HIV). These substances can be used in cell receptor studies and in transmembrane ion transport analysis. Because these compounds are secreted by skin glands,they can be easy obtained without injuring these animals. It is probable that amphibian skin constitutes a potential source of modern drugs.

  16. A bioinspired peptide scaffold with high antibiotic activity and low in vivo toxicity.

    Science.gov (United States)

    Rabanal, Francesc; Grau-Campistany, Ariadna; Vila-Farrés, Xavier; Gonzalez-Linares, Javier; Borràs, Miquel; Vila, Jordi; Manresa, Angeles; Cajal, Yolanda

    2015-05-29

    Bacterial resistance to almost all available antibiotics is an important public health issue. A major goal in antimicrobial drug discovery is the generation of new chemicals capable of killing pathogens with high selectivity, particularly multi-drug-resistant ones. Here we report the design, preparation and activity of new compounds based on a tunable, chemically accessible and upscalable lipopeptide scaffold amenable to suitable hit-to-lead development. Such compounds could become therapeutic candidates and future antibiotics available on the market. The compounds are cyclic, contain two D-amino acids for in vivo stability and their structures are reminiscent of other cyclic disulfide-containing peptides available on the market. The optimized compounds prove to be highly active against clinically relevant Gram-negative and Gram-positive bacteria. In vitro and in vivo tests show the low toxicity of the compounds. Their antimicrobial activity against resistant and multidrug-resistant bacteria is at the membrane level, although other targets may also be involved depending on the bacterial strain.

  17. Antifungal activity and gene expression of lipopeptide antibiotics in strains of genus Bacillus

    Directory of Open Access Journals (Sweden)

    Grabova A. Yu.

    2016-02-01

    Full Text Available Aim. To research the antifungal activity and gene expression of lipopeptide antibiotics in strains of genus Bacillus. Methods. Deferred antagonism method, PCR, qRT-PCR, MALDI-TOF mass spectrometry. Results. It was revealed that Bacillus sp. strains C6 and Lg37s out of five tested strains had the highest antifungal activity. Based on the molecular genetic methods, it was shown that the expression of genes of lipopeptide antibiotics, related to the fengycin family, occurred in all these strains. At the same time, the gene expression of cyclolipopeptide iturin was found in the Bacillus sp. strains C6 and Lg37s. It was determined that Bacillus sp. C6 strain had the highest level of expression of the fengycin operon`s genes, whereas the lowest level was observed in Bacillus sp. C10 strain. By means of MALDI-TOF mass spectrometry, the presence of fengycins in the cell-free cultural fluid of Bacillus sp. C6 strain was detected. Conclusion. The direct correlation between the level of antifungal activity and the fengycin synthetases expression has not been disclosed. A higher level of antagonism detected for two Bacillus strains is more likely associated with the expression and subsequent synthesis of fengycin and iturin.

  18. Frequency of Aminoglycoside-Resistance Genes in Methicillin-Resistant Staphylococcus aureus (MRSA) Isolates from Hospitalized Patients

    Science.gov (United States)

    Mahdiyoun, Seyed Mohsen; Kazemian, Hossein; Ahanjan, Mohammad; Houri, Hamidreza; Goudarzi, Mehdi

    2016-01-01

    Background Staphylococcus aureus is one of the most important causative agents in community- and hospital-acquired infections. Aminoglycosides are powerful bactericidal drugs that are often used in combination with beta-lactams or glycopeptides to treat staphylococcal infections. Objectives The main objective of the present study was to determine the prevalence of aminoglycoside resistance among methicillin-resistant Staphylococcus aureus (MRSA) isolates in hospitalized patients in Sari and Tehran, Iran. Methods In this study, 174 MRSA strains isolated from different clinical samples, such as blood, sputum, tracheal exudates, bronchus, pleura, urine, wounds, and catheters, were collected from hospitalized patients in Tehran and Sari during 2014. Antibiotic susceptibility testing was performed against nine antibiotics with the Kirby-Bauer disk diffusion method according to CLSI guidelines. The MRSA strains were examined with oxacillin and cefoxitin disks. MRSA was then validated by detection of the mecA gene. PCR was used to evaluate the prevalence of the aminoglycoside-resistance genes aac (6’)-Ie/aph (2”), aph (3’)-IIIa, and ant (4’) among the MRSA isolates. Results The results of drug susceptibility testing showed that the highest rate of resistance was against erythromycin in Tehran (84.4%) and gentamicin (71.7%) in Sari. All isolates were sensitive to vancomycin, and all strains harbored the mecA gene. The aac (6’)-Ie/aph (2”), aph (3’)-IIIa, and ant (4’)-Ia genes were detected among 134 (77%), 119 (68.4%), and 122 (70.1%) of the isolates, respectively. Conclusions The present study showed a high prevalence of aminoglycoside-resistance genes among MRSA isolates in two cities in Iran.

  19. Antimicrobial Activity of Gallium Protoporphyrin IX against Acinetobacter baumannii Strains Displaying Different Antibiotic Resistance Phenotypes.

    Science.gov (United States)

    Arivett, Brock A; Fiester, Steven E; Ohneck, Emily J; Penwell, William F; Kaufman, Cynthia M; Relich, Ryan F; Actis, Luis A

    2015-12-01

    A paucity of effective, currently available antibiotics and a lull in antibiotic development pose significant challenges for treatment of patients with multidrug-resistant (MDR) Acinetobacter baumannii infections. Thus, novel therapeutic strategies must be evaluated to meet the demands of treatment of these often life-threatening infections. Accordingly, we examined the antibiotic activity of gallium protoporphyrin IX (Ga-PPIX) against a collection of A. baumannii strains, including nonmilitary and military strains and strains representing different clonal lineages and isolates classified as susceptible or MDR. Susceptibility testing demonstrated that Ga-PPIX inhibits the growth of all tested strains when cultured in cation-adjusted Mueller-Hinton broth, with a MIC of 20 μg/ml. This concentration significantly reduced bacterial viability, while 40 μg/ml killed all cells of the A. baumannii ATCC 19606(T) and ACICU MDR isolate after 24-h incubation. Recovery of ATCC 19606(T) and ACICU strains from infected A549 human alveolar epithelial monolayers was also decreased when the medium was supplemented with Ga-PPIX, particularly at a 40-μg/ml concentration. Similarly, the coinjection of bacteria with Ga-PPIX increased the survival of Galleria mellonella larvae infected with ATCC 19606(T) or ACICU. Ga-PPIX was cytotoxic only when monolayers or larvae were exposed to concentrations 16-fold and 1,250-fold higher than those showing antibacterial activity, respectively. These results indicate that Ga-PPIX could be a viable therapeutic option for treatment of recalcitrant A. baumannii infections regardless of the resistance phenotype, clone lineage, time and site of isolation of strains causing these infections and their iron uptake phenotypes or the iron content of the media.

  20. 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.

  1. [Production of hydrolases by lactic acid bacteria and bifidobacteria and their antibiotic resistance].

    Science.gov (United States)

    Novik, G I; Astanovich, N I; Riabaia, N E

    2007-01-01

    It was demonstrated that bifidobacteria and lactic acid bacteria B. adolescentis and Lactobacillus sp. synthesized extracellular enzymes cleaving glycoside bonds in the molecules of dextran, pectic acid, and soluble starch. The maximal production of extracellular beta-galactosidase by B. adolescentis 91-BIM and 94-BIM at a rate of 0.08 and 0.03 U/mg h was observed during the exponential growth phase at 5 and 12 h of cultivation, respectively. The cultures of bifidobacteria retained 60-70% of beta-galactosidase and alpha-amylase activities after six months of storage. The bifidobacterium strains studied were resistant to amphotericin and aminoglycosides (gentamicin, kanamycin, and netromycin). The lactam antibiotics (ampicillin, benzylpenicillin, bicillin 3, bicillin 5, and carbenicillin), the preparations inhibiting protein synthesis at the level of ribosomes (lincomycin), RNA polymerase inhibitors (rifampin), cephalosporin, and Maxipime inhibited the growth of bifidobacteria. Rifampin, erythromycin, amphotericin, Maxipime, Fortum, doxycycline, levomycetin, streptomycin, and the aminoglycosides netromycin, gentamicin, and kanamycin did not have an effect on the growth of Lactobacillus sp., whereas semisynthetic derivatives of penicillin, carbenicillin and ampicillin, inhibited its growth as well as Oxamp and lincomycin. The lactam antibiotics benzylpenicillin, bicillin 3, and bicillin 5 inhibited the growth of lactic acid bacilli by 30-90%.

  2. Modulation of the antibiotic activity against multidrug resistant strains of coumarins isolated from Rutaceae species.

    Science.gov (United States)

    Madeiro, Sara A L; Borges, Nathalie H P B; Souto, Augusto L; de Figueiredo, Pedro T R; Siqueira-Junior, José P; Tavares, Josean F

    2017-03-01

    The first occurrences and dissemination of resistant microorganisms led to the inefficacy of many antibiotics, available in the market nowadays, therefore, the search for new substances with antimicrobial activity from natural sources has gained a great importance. The purpose of this work is to evaluate the antibacterial activity and modulation of drug resistance in Staphylococcus aureus by coumarins such as bergapten, xantotoxin, isopimpinellin and imperatorin obtained from two Rutaceae species (Metrodorea mollis and Pilocarpus spicatus). The antimicrobial activity was assessed based on the minimum inhibitory concentration (MIC), using the microdilution method. The MIC was >256 g/mL for all coumarins tested. Regarding the modulation of drug resistance assay, the isopimpinellin reducted the MIC of erytromicin by 4 times, whereas imperatorin exhibited the best result, reducing the MIC of tetracycline (2 times), erytomicin (4 times) and norfloxacin (4 times). By reducing the MIC of ethidium bromide, the imperatorin is consider in fact, as a putative efflux pump inhibitor of bacteria.

  3. C-Geranylated flavonoids from Paulownia tomentosa fruits with antimicrobial potential and synergistic activity with antibiotics.

    Science.gov (United States)

    Navrátilová, Alice; Nešuta, Ondřej; Vančatová, Irena; Čížek, Alois; Varela-M, Ruben E; López-Abán, Julio; Villa-Pulgarin, Janny A; Mollinedo, Faustino; Muro, Antonio; Žemličková, Helena; Kadlecová, Daniela; Šmejkal, Karel

    2016-08-01

    Context C-6-Geranylated flavonoids possess promising biological activities. These substances could be a source of lead compounds for the development of therapeutics. Objective The study was designed to evaluate their antibacterial and antileishmanial activity. Materials and methods C-6-Geranylated flavanones were tested in micromolar concentrations against promastigote forms of Leishmania brazilensis, L. donovani, L. infantum, and L. panamensis against methicillin-resistant Staphylococcus aureus (MRSA); and synergistic potential with antibiotics was analyzed. IC50 values (after 72 h) were calculated and compared with that of miltefosine. Flow cytometry and DNA fragmentation analysis were used the mechanism of the effect. Geranylated flavanones or epigallocatechin gallate were combined with oxacillin, tetracycline, and ciprofloxacin, and the effects of these two-component combinations were evaluated. Minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs) were established (after 24 h), the synergy was measured by the checkerboard titration technique, and the sums of the fractional inhibitory concentrations (∑FICs) were computed. Results 3'-O-Methyl-5'-O-methyldiplacone and 3'-O-methyldiplacone showed good antileishmanial activities (IC50 8-42 μM). 3'-O-Methyl-5'-hydroxydiplacone activates the apoptotic death at leishmanias, the effect of 3'-O-methyl-5'-O-methyldiplacone has another mechanism. The test of the antibacterial activity showed good effects of 3'-O-methyldiplacol and mimulone against MRSA (MIC 2-16 μg/mL), and in six cases, the results showed synergistic effects when combined with oxacillin. Synergistic effects were also found for the combination of epigallocatechin gallate with tetracycline or oxacillin. Conclusion This work demonstrates anti-MRSA and antileishmanial potential of geranylated flavanones and uncovers their promising synergistic activities with antibiotics. In addition, the mechanism of

  4. Evaluation of antibacterial activity and synergistic effect between antibiotic and the essential oils of some medicinal plants

    Institute of Scientific and Technical Information of China (English)

    Fadila Moussaoui; Tajelmolk Alaoui

    2016-01-01

    Objective:To demonstrate the in vitro antibacterial properties of five essential oils against ten bacterial strains and study the synergistic effect of the combination of essential oils with standard antibiotics.Methods:Origanum compactum,Chrysanthemum coronarium,Thymus willdenowii Boiss,Melissa officinalis and Origanum majorana L.were used alone and combined used with standard antibiotics to evaluate their antimicrobial activities.The disk diffusion method was employed.Results:The results showed that the combined application of the essential oils of the plants with antibiotics led to a synergistic effect in some cases,but antagonistic effect was also observed in some bacteria.Conclusions:This study shows that the combination of essential oils of the five plants with antibiotics may be useful in the fight against emerging microbial drug resistance.

  5. Evaluation of antibacterial activity and synergistic effect between antibiotic and the essential oils of some medicinal plants

    Institute of Scientific and Technical Information of China (English)

    Fadila Moussaoui; Tajelmolk Alaoui

    2016-01-01

    Objective: To demonstrate the in vitro antibacterial properties of five essential oils against ten bacterial strains and study the synergistic effect of the combination of essential oils with standard antibiotics. Methods: Origanum compactum, Chrysanthemum coronarium, Thymus willdenowii Boiss, Melissa officinalis and Origanum majorana L. were used alone and combined used with standard antibiotics to evaluate their antimicrobial activities. The disk diffusion method was employed. Results: The results showed that the combined application of the essential oils of the plants with antibiotics led to a synergistic effect in some cases, but antagonistic effect was also observed in some bacteria. Conclusions: This study shows that the combination of essential oils of the five plants with antibiotics may be useful in the fight against emerging microbial drug resistance.

  6. Antibiotic Resistance

    Science.gov (United States)

    ... lives. But there is a growing problem of antibiotic resistance. It happens when bacteria change and become able ... resistant to several common antibiotics. To help prevent antibiotic resistance Don't use antibiotics for viruses like colds ...

  7. Antibiotic Safety

    Science.gov (United States)

    ... are not effectively treated with an antibiotic • Viral gastroenteritis Bacterial infections should be treated with antibiotics. Some ... you antibiotics for a viral infection. Antibiotics kill bacteria, not viruses. • T ake all of your prescribed ...

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

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    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.

  9. Molecular basis of rare aminoglycoside susceptibility and pathogenesis of Burkholderia pseudomallei clinical isolates from Thailand.

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    Lily A Trunck

    Full Text Available BACKGROUND: Burkholderia pseudomallei is intrinsically resistant to aminoglycosides and macrolides, mostly due to AmrAB-OprA efflux pump expression. We investigated the molecular mechanisms of aminoglycoside susceptibility exhibited by Thai strains 708a, 2188a, and 3799a. METHODOLOGY/PRINCIPAL FINDINGS: qRT-PCR revealed absence of amrB transcripts in 708a and greatly reduced levels in 2188a and 3799a. Serial passage on increasing gentamicin concentrations yielded 2188a and 3799a mutants that became simultaneously resistant to other aminoglycosides and macrolides, whereas such mutants could not be obtained with 708a. Transcript analysis showed that the resistance of the 2188a and 3799a mutants was due to upregulation of amrAB-oprA expression by unknown mechanism(s. Use of a PCR walking strategy revealed that the amrAB-oprA operon was missing in 708a and that this loss was associated with deletion of more than 70 kb of genetic material. Rescue of the amrAB-oprB region from a 708a fosmid library and sequencing showed the presence of a large chromosome 1 deletion (131 kb and 141 kb compared to strains K96243 and 1710b, respectively. This deletion not only removed the amrAB-oprA operon, but also the entire gene clusters for malleobactin and cobalamin synthesis. Other genes deleted included the anaerobic arginine deiminase pathway, putative type 1 fimbriae and secreted chitinase. Whole genome sequencing and PCR analysis confirmed absence of these genes from 708a. Despite missing several putative virulence genes, 708a was fully virulent in a murine melioidosis model. CONCLUSIONS/SIGNIFICANCE: Strain 708a may be a natural candidate for genetic manipulation experiments that use Select Agent compliant antibiotics for selection and validates the use of laboratory-constructed Delta(amrAB-oprA mutants in such experiments.

  10. Nonparallel nephrotoxicity dose-response curves of aminoglycosides.

    OpenAIRE

    1981-01-01

    Nephrotoxicity comparisons of aminoglycosides in rats, utilizing large multiples of human doses, have indicated an advantage for netilmicin. However, no nephrotoxicity advantage of netilmicin has been demonstrated at the lower doses used in clinics. Some high-dose studies in rats have also suggested that the slope of the nephrotoxicity dose-response curve of netilmicin was less steep than the slopes of other aminoglycosides. Therefore, the slopes of the nephrotoxicity dose-response curves of ...

  11. Aminoglycosides prevent and dissociate the aggregation of platelets in patients with EDTA-dependent pseudothrombocytopenia.

    Science.gov (United States)

    Sakurai, S; Shiojima, I; Tanigawa, T; Nakahara, K

    1997-12-01

    Although EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) is of practical importance because failure to recognize this clinical entity may result in misdiagnosis and subsequent mismanagement of the patients, the pathophysiological nature of EDTA-PTCP remains unknown. To develop an effective way to evaluate the platelet counts in patients with EDTA-PTCP, we introduced aminoglycosides-supplemented anticoagulating agents. When kanamycin was pre-supplemented with EDTA for anticoagulating blood samples from EDTA-PTCP patients there was no significant change in the platelet counts and the morphology of blood cells after 150 min of incubation at room temperature. Furthermore, when kanamycin was added to EDTA-anticoagulated blood samples from EDTA-PTCP patients within 30 min after blood withdrawal, rapid dissociation of platelets without apparent morphological changes of blood cells was observed, and complete blood cell counts as well as the histogram patterns were almost the same as those examined immediately after blood sampling. The dissociation of aggregated platelets was also detected when other antibiotics were used, although it was associated with some extent of morphological changes of blood cells. These findings indicate that the supplementation of aminoglycosides either before or after blood sampling is a useful method for the diagnosis EDTA-PTCP and for the evaluation of platelet counts in patients with EDTA-PTCP.

  12. Extended-Interval Aminoglycoside Use in Cystic Fibrosis Exacerbation in Children and Young Adults

    Science.gov (United States)

    Safi, Khalid H.; Damiani, Justina M.; Sturza, Julie; Nasr, Samya Z.

    2016-01-01

    This is a prospective quality improvement project for patients with cystic fibrosis who are 5 years of age and older who were admitted for intravenous antibiotic administration as part of treatment of cystic fibrosis exacerbation. The goal of this project was to compare the pharmacokinetics of once-daily versus thrice-daily aminoglycoside use when treating cystic fibrosis exacerbation in different age groups. Of the total of 119 patient encounters, 82.4% were started on once-daily dosing, and the remainder were started on thrice-daily dosing. Patients with pharmacokinetics allowing the continuation of once-daily dosing differed from patients who required a switch to thrice-daily dosing in terms of baseline forced expiratory volume in 1 second, forced expiratory flow from 25% to 75% of vital capacity, age, and body mass index (BMI) but were similar in BMI percentiles. The once-daily dosing group had higher mean 18-hour level, higher mean half-life, higher mean area under the curve, and lower mean elimination constant. This study showed that aminoglycoside clearance is higher in younger children. PMID:27336007

  13. [High level of aminoglycoside resistance among Enterococcus faecalis and Enterococcus faecium strains].

    Science.gov (United States)

    Kozuszko, Sylwia; Białucha, Agata; Bogiel, Tomasz; Gospodarek, Eugenia

    2011-01-01

    Enterococcus sp. strains are believed as important reason of serious nosocomial infections currently. These infections are cured by using combination of beta-lactams and aminoglycosides for their treatment. Enterococcus sp. resistant to high-level doses of aminoglycosides, beta-lactams and vancomycin are responsible for therapeutic failure. The aim of our study was to evaluate the incidence of isolation and susceptibility to antibiotics of HLAR Enterococcus sp. strains isolated between 2007 and 2010 from the patients of University Hospital No. 1 of dr A. Jurasz Collegium Medicum of L. Rydygier in Bydgoszcz Nicolaus Copernicus University in Toruń. Amongst 6137 Enterococcus sp. strains 1124 (18,3%) presented HLAR phenotype; 53,1% of them was identified as E. faecalis and 46,9% as E. faecium. The highest percentage of all examined strains was isolated from the patients of different surgery clinics, Intensive Care Units, and Pediatrics, Hematology and Oncology Clinic. HLAR and HLSR phenotypes were noted in E. faecalis, for 45,7% and 27,5% strains, in E. faecium - 29,8% and 9,5%, respectively. HLGR phenotype was presented twice more often in E. faecium than E. faecalis. Highest percentages of E. faecium resistant to glycopeptides and rifampicin were observed when compared with E. faecalis. The highest percentages of strains intermediate, resistant to vancomycin and resistant to glycopeptides were noted for E. faecium strains with phenotypes HLAR, HLGR and HLSR.

  14. In vitro antibiotic susceptibilities of Burkholderia mallei (causative agent of glanders) determined by broth microdilution and E-test.

    Science.gov (United States)

    Heine, H S; England, M J; Waag, D M; Byrne, W R

    2001-07-01

    In vitro susceptibilities to 28 antibiotics were determined for 11 strains of Burkholderia mallei by the broth microdilution method. The B. mallei strains demonstrated susceptibility to aminoglycosides, macrolides, quinolones, doxycycline, piperacillin, ceftazidime, and imipenem. For comparison and evaluation, 17 antibiotic susceptibilities were also determined by the E-test. E-test values were always lower than the broth dilution values. Establishing and comparing antibiotic susceptibilities of specific B. mallei strains will provide reference information for assessing new antibiotic agents.

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

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    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.

  16. Origin in Acinetobacter guillouiae and dissemination of the aminoglycoside-modifying enzyme Aph(3')-VI.

    Science.gov (United States)

    Yoon, Eun-Jeong; Goussard, Sylvie; Touchon, Marie; Krizova, Lenka; Cerqueira, Gustavo; Murphy, Cheryl; Lambert, Thierry; Grillot-Courvalin, Catherine; Nemec, Alexandr; Courvalin, Patrice

    2014-10-21

    The amikacin resistance gene aphA6 was first detected in the nosocomial pathogen Acinetobacter baumannii and subsequently in other genera. Analysis of 133 whole-genome sequences covering the taxonomic diversity of Acinetobacter spp. detected aphA6 in the chromosome of 2 isolates of A. guillouiae, which is an environmental species, 1 of 8 A. parvus isolates, and 5 of 34 A. baumannii isolates. The gene was also present in 29 out of 36 A. guillouiae isolates screened by PCR, indicating that it is ancestral to this species. The Pnative promoter for aphA6 in A. guillouiae and A. parvus was replaced in A. baumannii by PaphA6, which was generated by use of the insertion sequence ISAba125, which brought a -35 sequence. Study of promoter strength in Escherichia coli and A. baumannii indicated that PaphA6 was four times more potent than Pnative. There was a good correlation between aminoglycoside MICs and aphA6 transcription in A. guillouiae isolates that remained susceptible to amikacin. The marked topology differences of the phylogenetic trees of aphA6 and of the hosts strongly support its recent direct transfer within Acinetobacter spp. and also to evolutionarily remote bacterial genera. Concomitant expression of aphA6 must have occurred because, contrary to the donors, it can confer resistance to the new hosts. Mobilization and expression of aphA6 via composite transposons and the upstream IS-generating hybrid PaphA6, followed by conjugation, seems the most plausible mechanism. This is in agreement with the observation that, in the recipients, aphA6 is carried by conjugative plasmids and flanked by IS that are common in Acinetobacter spp. Our data indicate that resistance genes can also be found in susceptible environmental bacteria. Importance: We speculated that the aphA6 gene for an enzyme that confers resistance to amikacin, the most active aminoglycoside for the treatment of nosocomial infections due to Acinetobacter spp., originated in this genus before

  17. Understanding the origins of bacterial resistance to aminoglycosides through molecular dynamics mutational study of the ribosomal A-site.

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    Julia Romanowska

    2011-07-01

    Full Text Available Paromomycin is an aminoglycosidic antibiotic that targets the RNA of the bacterial small ribosomal subunit. It binds in the A-site, which is one of the three tRNA binding sites, and affects translational fidelity by stabilizing two adenines (A1492 and A1493 in the flipped-out state. Experiments have shown that various mutations in the A-site result in bacterial resistance to aminoglycosides. In this study, we performed multiple molecular dynamics simulations of the mutated A-site RNA fragment in explicit solvent to analyze changes in the physicochemical features of the A-site that were introduced by substitutions of specific bases. The simulations were conducted for free RNA and in complex with paromomycin. We found that the specific mutations affect the shape and dynamics of the binding cleft as well as significantly alter its electrostatic properties. The most pronounced changes were observed in the U1406C∶U1495A mutant, where important hydrogen bonds between the RNA and paromomycin were disrupted. The present study aims to clarify the underlying physicochemical mechanisms of bacterial resistance to aminoglycosides due to target mutations.

  18. Study of Klebsiella pneumoniae producing extended-spectrum β-lactamases against aminoglycosides

    Institute of Scientific and Technical Information of China (English)

    WEI FENG SHI; SU JIAN WANG; JIAN PING QIN

    2007-01-01

    Klebsiella pneumoniae ( K. pneumoniae) is one of the main gram-negative bacilli in clinical practice. Nosocomial infections caused by K. pneumoniae producing extended-spectrum β-lactamases (ESBLs) are very difficult to treat. This paper investigated the resistant characteristics of K. pneumoniae producing ESBLs and their aminoglycoside-modifying enzyme gene expressions including Nacetyltransferases and O-adenyhransferases. Bacteria identification and ESBLs confirmatory tests were performed by Phoenix TM-100 system. And minimum inhibitory concentrations (MICs) of gentamicin,amikacin, kanamycin, tobramycin, netilmicin and neomycin in 53 K. pneumoniae isolates were detected by agar dilution. In addition, six aminoglycoside-modifying enzyme genes were amplified by polymerase chain reaction (PCR) and verified by DNA sequencer. It was found that imipenem and meropenem against 120 K. pneumoniae isolates produced powerful antimicrobial activities. The resistant rates of gentamicin and amikacin were 55.0% and 46.7%, respectively. Except neomycin,MIC50 and MIC90 of gentamicin, amikacin, kanamycin, tobramycin and netilmicin in 53 K. pneumoniae were all > 128 μg/ml, and the resistant rates were 83.0%, 52.3%, 75.5%, 81. 1% and 69.8%, respectively. However, neomycin was only 39.6%. In addition, five modifying enzyme genes, including aac(3)- Ⅰ , aac(3)-Ⅱ, aac(6′) - Ⅰ b, ant(3″) - Ⅰ, ant(2″) - Ⅰ genes, were found in 53 isoahes except aac (6′)-Ⅱ, and their positive rates were 11.3%, 67.9%, 47.2%,1.9 % and 39.6 %, respectively. It was also confirmed by nucleotide sequence analysis that the above resistant genes shared nearly 100% identities with GenBank published genes. The results obtained in the present study indicated that K. pneumoniae producing ESBLs strains are rapidly spreading in our hospital, and their resistance to aminoglycosides may be associated with aminoglycoside-modifying enzyme gene expressions.

  19. An MRPS12 mutation modifies aminoglycoside sensitivity caused by 12S rRNA mutations

    Directory of Open Access Journals (Sweden)

    Sonia eEmperador

    2015-01-01

    Full Text Available Several homoplasmic pathologic mutations in mitochondrial DNA, such as those causing Leber hereditary optic neuropathy or non-syndromic hearing loss, show incomplete penetrance. Therefore, other elements must modify their pathogenicity. Discovery of these modifying factors is not an easy task because in multifactorial diseases conventional genetic approaches may not always be informative.Here, we have taken an evolutionary approach to unmask putative modifying factors for a particular homoplasmic pathologic mutation causing aminoglycoside-induced and non-syndromic hearing loss, the m.1494C>T transition in the mitochondrial DNA. The mutation is located in the decoding site of the mitochondrial ribosomal RNA. We first looked at mammalian species that had fixed the human pathologic mutation. These mutations are called compensated pathogenic deviations because an organism carrying one must also have another that suppresses the deleterious effect of the first. We found that species from the primate family Cercopithecidae (old world monkeys harbor the m.1494T allele even if their auditory function is normal.In humans the m.1494T allele increases the susceptibility to aminoglycosides. However, in primary fibroblasts from a Cercopithecidae species, aminoglycosides do not impair cell growth, respiratory complex IV activity and quantity or the mitochondrial protein synthesis. Interestingly, these species also carry a fixed mutation in the mitochondrial ribosomal protein S12. We show that the expression of this variant in a human m.1494T cell line reduces its susceptibility to aminoglycosides. Because several mutations in this human protein have been described, they may possibly explain the absence of pathologic phenotype in some pedigree members with the most frequent pathologic mutations in mitochondrial ribosomal RNA.

  20. 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

    2016-12-16

    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.

  1. European Antibiotic Awareness Day, 2008 - the first Europe-wide public information campaign on prudent antibiotic use: methods and survey of activities in participating countries.

    NARCIS (Netherlands)

    Earnshaw, S.; Monnet, D.L.; Duncan, B.; O'Toole, J.; Ekdahl, K.; Goossens, H.

    2009-01-01

    Antibiotic resistance is a major European and global public health problem and is, for a large part, driven by misuse of antibiotics. Hence, reducing unnecessary antibiotic use, particularly for the treatment of certain respiratory tract infections where they are not needed, is a public health prior

  2. Impact of kanamycin on melanogenesis and antioxidant enzymes activity in melanocytes--an in vitro study.

    Science.gov (United States)

    Wrześniok, Dorota; Otręba, Michał; Beberok, Artur; Buszman, Ewa

    2013-12-01

    Aminoglycosides, broad spectrum aminoglycoside antibiotics, are used in various infections therapy due to their good antimicrobial characteristics. However, their adverse effects such as nephrotoxicity and auditory ototoxicity, as well as some toxic effects directed to pigmented tissues, complicate the use of these agents. This study was undertaken to investigate the effect of aminoglycoside antibiotic-kanamycin on viability, melanogenesis and antioxidant enzymes activity in cultured human normal melanocytes (HEMa-LP). It has been demonstrated that kanamycin induces concentration-dependent loss in melanocytes viability. The value of EC50 was found to be ~6.0 mM. Kanamycin suppressed melanin biosynthesis: antibiotic was shown to inhibit cellular tyrosinase activity and to reduce melanin content in normal human melanocytes. Significant changes in the cellular antioxidant enzymes: SOD, CAT and GPx were stated in melanocytes exposed to kanamycin. Moreover, it was observed that kanamycin caused depletion of antioxidant defense sytem. It is concluded that the inhibitory effect of kanamycin on melanogenesis and not sufficient antioxidant defense mechanism in melanocytes in vitro may explain the potential mechanisms of undesirable side effects of this drug directed to pigmented tissues in vivo.

  3. ANTIBACTERIAL ACTIVITY OF SOME WILD MEDICAL PLANTS EXTRACT TO ANTIBIOTIC RESISTANT ESCHERICHIA COLI

    OpenAIRE

    Lukáš Hleba; Miroslava Kačániová; Jana Petrová; Soňa Felšӧciová; Adriana Pavelková; Katarína Rovná

    2013-01-01

    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 resi...

  4. Prophylactic antibiotic regimens in tumor surgery (PARITY survey

    Directory of Open Access Journals (Sweden)

    Hasan Khaled

    2012-06-01

    Full Text Available Abstract Background Deep infection following endoprosthetic limb reconstruction for sarcoma of the long bones is a devastating complication occurring in 15% of sarcoma patients. Optimizing infection protocols and conducting definitive surgical trials are critical to improving outcomes. In this study, the PARITY (Prophylactic Antibiotic Regimens in Tumor Surgery investigators aimed to examine surgeon preferences in antibiotic prophylaxis and perceptions about current evidence, as well as to ascertain interest in resolving uncertainty in the evidence with clinical trials. Methods We used a cross-sectional survey to examine current practice in the prescription of prophylactic antibiotics in Musculoskeletal Tumor Surgery. The survey was approved by our institution’s Ethics Board and emailed to all Active Members of the Musculoskeletal Tumor Society (MSTS and Canadian Orthopaedic Oncology Society (CANOOS. Survey answers were collected using an anonymous online survey tool. Results Of the 96 surgeons who received the questionnaire, 72 responded (75% response rate (% CI: 65.5, 82.5%. While almost all respondents agreed antibiotic regimens were important in reducing the risk of infection, respondents varied considerably in their choices of antibiotic regimens and dosages. Although 73% (95% CI: 61, 82% of respondents prescribe a first generation cephalosporin, 25% favor additional coverage with an aminoglycoside and/or Vancomycin. Of those who prescribe a cephalosporin, 33% prescribe a dosage of one gram for all patients and the reminder prescribe up to 2 grams based on body weight. One in three surgeons (95% CI: 25, 48% believes antibiotics could be discontinued after 24 hours but 40% (95% CI: 30, 53% continue antibiotics until the suction drain is removed. Given the ongoing uncertainty in evidence to guide best practices, 90% (95% CI: 81, 95% of respondents agreed that they would change their practice if a large randomized controlled trial showed

  5. Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities.

    Science.gov (United States)

    Cushnie, T P Tim; Cushnie, Benjamart; Lamb, Andrew J

    2014-11-01

    With reports of pandrug-resistant bacteria causing untreatable infections, the need for new antibacterial therapies is more pressing than ever. Alkaloids are a large and structurally diverse group of compounds that have served as scaffolds for important antibacterial drugs such as metronidazole and the quinolones. In this review, we highlight other alkaloids with development potential. Natural, semisynthetic and synthetic alkaloids of all classes are considered, looking first at those with direct antibacterial activity and those with antibiotic-enhancing activity. Potent examples include CJ-13,136, a novel actinomycete-derived quinolone alkaloid with a minimum inhibitory concentration of 0.1 ng/mL against Helicobacter pylori, and squalamine, a polyamine alkaloid from the dogfish shark that renders Gram-negative pathogens 16- to >32-fold more susceptible to ciprofloxacin. Where available, information on toxicity, structure-activity relationships, mechanisms of action and in vivo activity is presented. The effects of alkaloids on virulence gene regulatory systems such as quorum sensing and virulence factors such as sortases, adhesins and secretion systems are also described. The synthetic isoquinoline alkaloid virstatin, for example, inhibits the transcriptional regulator ToxT in Vibrio cholerae, preventing expression of cholera toxin and fimbriae and conferring in vivo protection against intestinal colonisation. The review concludes with implications and limitations of the described research and directions for future research.

  6. Synthesis, cytotoxicity and antibacterial activity of new esters of polyether antibiotic - salinomycin.

    Science.gov (United States)

    Antoszczak, Michał; Popiel, Katarzyna; Stefańska, Joanna; Wietrzyk, Joanna; Maj, Ewa; Janczak, Jan; Michalska, Greta; Brzezinski, Bogumil; Huczyński, Adam

    2014-04-09

    A series of 12 novel ester derivatives of naturally occurring polyether antibiotic - salinomycin were synthesized, characterised by spectroscopic method and evaluated for their in vitro antibacterial activity and cytotoxicity. The new esters were demonstrated to form complexes with monovalent and divalent metal cation of 1:1 stoichiometry in contrast to the salinomycin which forms only complexes with monovalent cations. All the obtained compounds show potent antiproliferative activity against human cancer cell lines and a good selectivity index for cancer versus mammalian cells. Additionally, 3 compounds showed higher antiproliferative activity against the drug-resistant cancer cells and lower toxicity towards normal cells than those of unmodified salinomycin and standard anticancer drugs such as cisplatin and doxorubicin. Some of the synthesized compounds showed good inhibitory activity against Staphylococcus strains and clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE). These studies show that salinomycin esters are interesting scaffolds for the development of novel anticancer and Gram-positive antibacterial agents.

  7. Antibacterial activity of some medicinal mangroves against antibiotic resistant pathogenic bacteria

    Directory of Open Access Journals (Sweden)

    Abeysinghe P

    2010-01-01

    Full Text Available The antibacterial activity of the leaves and bark of mangrove plants, Avicennia marina, A. officinalis, Bruguiera sexangula, Exoecaria agallocha, Lumnitzera racemosa, and Rhizophora apiculata was evaluated against antibiotic resistant pathogenic bacteria, Staphylococcus aureus and Proteus sp. Soxhlet extracts of petroleum ether, ethyl acetate, ethanol and water were prepared and evaluated the antibacterial activity using agar diffusion method. Most of the plant extracts showed promising antibacterial activity against both bacterial species. However, higher antibacterial activity was observed for Staphylococcus aureus than Proteus sp. The highest antibacterial activity was shown by ethyl acetate of mature leaf extracts of E. agallocha for Staphylococcus aureus. All ethyl acetate extracts showed higher inhibition against S. aureus while some extracts of chloroform, ethyl acetate and ethanol gave inhibition against Proteus sp. None of the petroleum ether and aqueous extracts showed inhibition against Proteus sp. All fresh plant materials did also show more antibacterial activity against both bacterial strains than did dried plant extracts. Antibacterial activity of fresh and dried plant materials reduced for both bacterial strains with time after extraction. Since L. racemosa and A. marina gave the best inhibition for bacterial species, they were used for further investigations. Charcoal treated plant extracts of L. racemosa and A. marina were able to inhibit both bacterial strains more than those of untreated plant extracts. Phytochemical screening of mature leaf, bark of L. racemosa and leaf extracts of A. marina has been carried out and revealed that leaf and bark contained alkaloids, steroids, triterpenoids and flavonoids. None of the above extracts indicate the presence of saponins and cardiac glycosides. Separated bands of extracts by TLC analysis showed antibacterial activity against S. aureus.

  8. Distribution of innate efflux-mediated aminoglycoside resistance among different Achromobacter species

    Directory of Open Access Journals (Sweden)

    J. Bador

    2016-03-01

    Full Text Available Achromobacter spp. are emerging respiratory pathogens in cystic fibrosis patients. Since 2013 the genus Achromobacter includes 15 species for which innate antibiotic resistance is unknown. Previously the AxyXY-OprZ efflux system has been described to confer aminoglycoside (AG resistance in A. xylosoxidans. Nevertheless, some Achromobacter spp. strains are susceptible to AG. This study including 49 Achromobacter isolates reveals that AG resistance is correlated with different Achromobacter spp. It is noteworthy that the axyXY-oprZ operon is detected only in AG-resistant species, including the most frequently encountered in cystic fibrosis patients: A. xylosoxidans, A. ruhlandii, A. dolens and A. insuavis.

  9. Factors impacting the aminoglycoside-induced UGA stop codon readthrough in selenoprotein translation.

    Science.gov (United States)

    Martitz, Janine; Hofmann, Peter Josef; Johannes, Jörg; Köhrle, Josef; Schomburg, Lutz; Renko, Kostja

    2016-09-01

    Aminoglycosides (AG) are oligosaccharide antibiotics that interfere with the small ribosomal subunit in aerobic, Gram-negative bacteria, causing pathogen-destructing error rates in their protein biosynthesis. Aminoglycosides also induce mRNA misinterpretation in eukaryotic cells, especially of the UGA (Opal)-stop codon, albeit to a lower extent. UGA recoding is essentially required for the incorporation of selenocysteine (Sec) into growing selenoproteins during translation. Selenocysteine incorporation requires the presence of a selenoprotein-specific stem-loop structure within the 3'-untranslated region of the mRNA, the so-called Sec-insertion sequence (SECIS) element. Interestingly, selenoprotein genes differ in their SECIS-element sequence and in their UGA base context. We hypothesized that the SECIS-element and the specific codon context synergize in controlling the effects of AG on stop codon readthrough. To this end, the SECIS-elements of glutathione peroxidase 1, glutathione peroxidase 4 and selenoprotein P transcripts were cloned into a reporter system and analyzed in combination with different UGA codon contexts. Our results indicate that a cytosine in position 4 (directly downstream of UGA) confers strongest effects on both the Se- and AG-dependent readthrough. Overall selenoprotein biosynthesis rate depends on the Se-status, AG concentration and the specific SECIS-element present in the transcript. These findings help to get a better understanding for the susceptibility of different transcripts towards AG-mediated interference with the biosynthesis of functional Se-containing selenoproteins, and highlight the importance of the Se-status for successful selenoprotein biosynthesis under antibiotic therapy.

  10. 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.

  11. Antibiotic pigment from desert soil actinomycetes; biological activity, purification and chemical screening

    Directory of Open Access Journals (Sweden)

    Selvameenal L

    2009-01-01

    Full Text Available An actinomycete strain, Streptomyces hygroscopicus subsp. ossamyceticus (strain D10 was isolated from Thar Desert soil, Rajasthan during the year 2006 and found to produce a yellow color pigment with antibiotic activity. Crude pigment was produced from strain D10 by solid state fermentation using wheat bran medium followed by extraction with ethyl acetate. The antimicrobial activity of the crude pigment was evaluated against drug resistant pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Staphylococcus aureus, extended spectrum b-lactamase producing cultures of Escherichia coli, Pseudomonas aeruginosa and Klebsiella sp. About 420 mg of crude pigment was produced per 10 g of wheat bran medium. In the disc diffusion method the crude ethyl acetate extract showed a minimum of 10 mm inhibition against Klebsiella sp. and maximum of 19 mm of inhibition against Escherichia coli. The crude pigment was partially purified using thin layer chromatography with the solvent system chloroform:methanol (30:70 and the Rf value was calculated as 0.768. Antimicrobial activity of the partially purified compound from thin layer chromatography was determined using the bioautography method. The purified pigment showed minimum of 15 mm inhibition against Klebsiella sp. and a maximum of 23 mm of inhibition against vancomycin-resistant Staphylococcus aureus in the disc diffusion method. Based on the results of chemical screening, the pigment was tentatively identified as group of sugar containing molecules.

  12. Antimicrobial Activity of Piper gaudichaudianum Kuntze and Its Synergism with Different Antibiotics

    Directory of Open Access Journals (Sweden)

    Benedito Prado Dias Filho

    2011-12-01

    Full Text Available One of the oldest forms of medical practice is the use of plants for the treatment and prevention of diseases that affect humans. We have studied the antimicrobial activity and synergism of Piper gaudichaudianum Kuntze with different antibiotics. The crude extract from the leaves of P. gaudichaudianum was submitted to chromatographic separation, resulting in five fractions. Fraction F3 contained a chromone (2,2-dimethyl-6-carboxycroman-4-one, and fraction F2 contained isomers that are prenylated derivatives of benzoic acid [4-hydroxy-(3',7'-dimethyl-1'-oxo-octa-E-2'-6'-dienylbenzoic acid and 4-hydroxy-(3',7'-dimethyl-1'-oxo-octa-2'-Z-6'-dienyl benzoic acid]. The chemical structures of both compounds were determined by analysis of 1H-NMR, 13C-NMR, COZY, DEPT, HMQC, and HMBC spectral data, and by comparison with data in the literature. The crude extract, fraction F2, and fraction F3 showed good activity against Staphylococcus aureus, Bacillus subtilis, and Candida tropicalis. The two benzoic acid derivatives only showed activity against S. aureus and B. subtilis. The bioauthographic analysis showed an inhibition zone only in fraction F2. Fractions F2 and F3 showed synergism in combination with ceftriaxone, tetracycline, and vancomycin. Morphological changes in form and structure were found by scanning electron microscopy in S. aureus treated with the combination of fraction F2 with vancomycin.

  13. Antibacterial activity of Thymus maroccanus and Thymus broussonetii essential oils against nosocomial infection - bacteria and their synergistic potential with antibiotics.

    Science.gov (United States)

    Fadli, Mariam; Saad, Asmaa; Sayadi, Sami; Chevalier, Jacqueline; Mezrioui, Nour-Eddine; Pagès, Jean-Marie; Hassani, Lahcen

    2012-03-15

    The aim of this study was to evaluate the antibacterial effect of the association between conventional antibiotics and essential oils (EOs) of endemic Moroccan thyme species, Thymus maroccanus and T. broussonetii, on antibiotic-resistant bacteria involved in nosocomial infections. Synergistic interactions between antibiotics (ciprofloxacin, gentamicin, pristinamycin, and cefixime) and EOs, and between T. maroccanus and T. Broussonetii EOs were determined by the checkerboard test. Serial dilutions of two antimicrobial agents were mixed together so that each row (and column) contained a fixed amount of the first agent and increasing amounts of the second one. The results indicate that the oils had a high inhibitory activity against tested bacteria, except for Pseudomonas aeruginosa. In parallel with the increase of cellular killing, the release of 260nm-absorbing materials from bacterial cells, treated with EOs, increased in response to oil concentration. Out of 80 combinations tested between EOs and antibiotics, 71% showed total synergism, 20% had partial synergistic interaction and 9% showed no effect. Combination with carvacrol, the major constituent of T. maroccanus and T. broussonetii, showed also an interesting synergistic effect in combination with ciprofloxacin. The effect on Gram-positive bacteria was more important than on Gram-negative bacteria. These findings are very promising since the use of these combinations for nosocomial infections treatment is likely to reduce the minimum effective dose of the antibiotics, thus minimizing their possible toxic side effects and treatment cost. However, further investigations are needed to assess the potential for therapeutic application.

  14. 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.

  15. Comparative Evaluation of the Modulation of Antibiotic-Activity against Strains of Escherichia coli and Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Henrique D. M. Coutinho

    2015-09-01

    Full Text Available Introduction: Combining multiple drugs is an strategy used to combat the dissemination of pathogenic and drug resistant bacteria. However, the misuse of these drugs against bacteria have caused the selection of more resistant specimens called multidrug-resistant bacteria. Objective: In this work we evaluated the antibiotic activity of claritromicin, gentamicin, ciprofloxacin and imipenen, alone or associating one by one, against strains of Escherichia coli and Staphylococcus aureus. Material and methods: The minimal inhibitory concentration (mic was performed us­ing the microdilution assay. Based in the mic values, the antibiotic effect of the drugs alone and in association were determined. Results: The association between the drugs demonstrated the synergism against the bacterial strains. Conclusion: The use of the combined antibiotic-therapy can be positively performed, but additional studies have to be conducted first for proving that its use is safe.

  16. Antibiotics Quiz

    Science.gov (United States)

    ... on the Farm Get Smart About Antibiotics Week Antibiotics Quiz Recommend on Facebook Tweet Share Compartir Try ... right of the answer you think is correct. Antibiotic Quiz Widget Copy the code for this widget, ...

  17. 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.

  18. Relationship between antimicrobial resistance and aminoglycoside-modifying enzyme gene expressions in Acinetobacter baumannii

    Institute of Scientific and Technical Information of China (English)

    SHI Wei-feng; JIANG Jian-ping; MI Zu-huang

    2005-01-01

    Background Acinetobacter baumannii is one of the main gram-negative bacilli in clinical practice. Nosocomial infections caused by multi-drug resistance Acinetobacter baumannii is very difficult to treat. This study was designed to investigate the antimicrobial resistance characteristics and four resistant gene expressions of aminoglycoside-modifying enzymes including N-acetyltransferases and O-phosphotransferases in Acinetobacter baumannii. Methods Bacterial identification and antimicrobial susceptibility test were performed by PhoenixTM system in 247 strains of Acinetobacter baumannii. Minimal inhibitory concentrations (MICs) of seven aminoglycosides including gentamicin, amikacin, kanamycin, tobramycin, netilmicin, neomycin and streptomycin in 15 strains of multi-drug resistant Acinetobacter baumannii were detected by agar dilution. Four aminoglycoside-modifying enzyme genes were amplified by polymerase chain reaction (PCR) and verified by DNA sequencer.Results The resistance rates of 247 strains of Acinetobacter baumannii against cefotaxime, levofloxacin, piperacillin, aztreonam, tetracycline, ciprofloxacin and chloramphenicol were more than 50%. Imipenem and meropenem showed high antibacterial activities with resistance rates of 3.2% and 4.1%. MIC50 and MIC90 of gentamicin, amikacin, streptomycin and kanamycin in 15 strains of multi-drug resistant Acinetobacter baumanii were all more than 1024 mg/L, and the resistance rates were 100%, 100%, 100% and 93.3%, respectively. But their resistance rates to tobramycin, netilmicin and neomycin were 86.7%, 93.3% and 46.7%, respectively. Three modifying enzyme genes, including aacC1, aacC2 and aacA4 genes, were found in 15 strains, but aphA6 had not been detected. Their positive rates were 93.3%, 20.0% and 20.0%, respectively. These three genes existed simultaneously in No.19 strain. Nucleotide sequences of aacC1, aacC2 and aacA4 genes shared 100%, 97.9% and 99.7% identities with GenBank genes (AY307113, S68058 and AY

  19. 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.

  20. Thermo activated persulfate oxidation of antibiotic sulfamethoxazole and structurally related compounds.

    Science.gov (United States)

    Ji, Yuefei; Fan, Yan; Liu, Kuo; Kong, Deyang; Lu, Junhe

    2015-12-15

    The widespread occurrence of sulfonamides (e.g., sulfamethoxazole) in natural environment has raised growing concerns due to their potential to induce antibiotic-resistant genes. In this study, the degradation of SMX and related sulfonamides by thermo activated persulfate (PS) oxidation was investigated. Experimental results demonstrated that SMX degradation followed pseudo-first-order reaction kinetics. The pseudo-first-order rate constant (k(obs)) was increased markedly with increasing temperature and pH. The presence of bicarbonate manifested promoting effect on SMX degradation while fulvic acid reduced it. Radical scavenging tests revealed that the predominant oxidizing species was SO4(•-) at neutral pH. Aniline moiety in SMX molecule was confirmed to be the primary reactive site for SO4(•-) attack by comparison with substructural analogues. Reaction products were enriched by solid phase extraction (SPE) and analyzed by liquid chromatography-electrospray ionization-triple quadrupole mass spectrometry (LC-ESI-MS/MS). A total of 7 products derived from hydroxylation, sulfonamide S-N bond cleavage, aniline moiety oxidation and coupling reaction were identified, and transformation pathways of SMX oxidation were proposed. Degradation of sulfonamides was appreciably influenced by the heterocyclic ring present in the molecules. Results reveal that thermo activated PS oxidation could be an efficient approach for remediation of water contaminated by SMX and related sulfonamides.

  1. Quinazoline derivatives are efficient chemosensitizers of antibiotic activity in Enterobacter aerogenes, Klebsiella pneumoniae and Pseudomonas aeruginosa resistant strains.

    Science.gov (United States)

    Chevalier, Jacqueline; Mahamoud, Abdallah; Baitiche, Milad; Adam, Elissavet; Viveiros, Miguel; Smarandache, Adriana; Militaru, Andra; Pascu, Mihail L; Amaral, Leonard; Pagès, Jean-Marie

    2010-08-01

    Amongst the three series of quinazoline derivatives synthesised and studied in this work, some molecules increase the antibiotic susceptibility of Gram-negative bacteria presenting multidrug-resistant phenotypes. N-alkyl compounds induced an increase in the activity of chloramphenicol, nalidixic acid and sparfloxacin, which are substrates of the AcrAB-TolC and MexAB-OprM efflux pumps in clinical isolates. These molecules are able to increase the intracellular concentration of chloramphenicol in efflux pump-overproducing strains. Their activity depends on the antibiotic structure, suggesting that different sites may be involved for the recognition of substrates by a given efflux pump. Quinazoline molecules exhibiting a nitro functional group are more active, and structure-activity relationship studies may be undertaken to identify the pharmacophoric group involved in the AcrB and MexB affinity sites.

  2. UCH9, a new antitumor antibiotic produced by Streptomyces: I. Producing organism, fermentation, isolation and biological activities.

    Science.gov (United States)

    Ogawa, H; Yamashita, Y; Katahira, R; Chiba, S; Iwasaki, T; Ashizawa, T; Nakano, H

    1998-03-01

    We developed a microbial prescreen using Bacillus stearothermophilus NUB3620 and bacteriophage TP-68 to detect potential antitumor compounds acting on DNA or topoisomerases. During the course of screening microbial cultures for their antibacteriophage activities, we found that Streptomyces sp. isolated from a soil sample collected in Iwakuni city, Yamaguchi prefecture, Japan, produced a new antitumor antibiotic, UCH9. UCH9 was isolated from culture broth by a combination of EtOAc extraction and column chromatography. UCH9 has a new structure related to the antitumor antibiotic chromomycins. It exhibited antimicrobial activity against Gram-positive organisms. UCH9 also showed cytotoxic activity against HeLa S3 cells with an IC50 value of 13 nM and exhibited antitumor activity in vivo against mouse leukemia P388.

  3. Antimicrobial activity of the essential oil and different fractions of Juniperus communis L. and a comparison with some commercial antibiotics

    Directory of Open Access Journals (Sweden)

    SANDRA B. GLIIC

    2007-04-01

    Full Text Available The essential oil of common juniper (Juniperus communis L., from the southern part of Serbia and its fractions of different composition, as well as commercial antibiotics were used for testing their antimicrobial activity against bacteria, yeast and fungi. The essential oil was produced by hydro-distillation in a pilot plant (130 dm3 and then fractionated by distillation over a column, with 36 theoretical stages, under vacuum (26–66 mbar. The essential oil was also fractionated using pure CO2 or CO2 and methanol as co-solvent under supercritical conditions. The native oil showed weak antimicrobial activity, while the fractions with a high content of a-pinene, and mixture of a-pinene and sabinene showed the highest antimicrobial activity, especially against fungi. In comparison to the commercial antibiotics, the oil fractions showed more extensive spectra of antimicrobial activity, as well as wider inhibition zones.

  4. Electrochemical oxidation of fluoroquinolone antibiotics: Mechanism, residual antibacterial activity and toxicity change.

    Science.gov (United States)

    Zhu, Linyan; Santiago-Schübel, Beatrix; Xiao, Hongxia; Hollert, Henner; Kueppers, Stephan

    2016-10-01

    In this paper, we studied the electrochemical oxidation mechanisms of three typical fluoroquinolone antibiotics (FQs), and investigated residual antibacterial activity and toxicity changes after oxidation processes. Electrochemistry coupled to mass spectrometry (EC-MS) was used to study the oxidation processes of ciprofloxacin (CIP), norfloxacin (NOR) and ofloxacin (OFL). Eight oxidation products for each parent compound were identified and their chemical structures were elucidated. The transformation trend of each product, with the continuous increase of voltage from 0 to 3000 mV, was recorded by online EC-MS. The oxidation pathways were proposed based on the structural information and transformation trends of oxidation products. We found the oxidation mechanisms of FQs consisted of the hydroxylation and cleavage of piperazinyl ring via reactions with hydroxyl radicals, while the fluoroquinolone core remained intact. The antibacterial activity of the parent compounds and their oxidation mixtures was estimated using zone inhibition tests for gram-negative bacteria Salmonella typhimurium. It was found that the oxidation mixtures of CIP and NOR retained the antibacterial properties with lower activity compared to their parent compounds, while the antibacterial activity of OFL was almost eliminated after oxidation. Furthermore, the toxicity of the three FQs and their oxidation mixtures were evaluated using algal growth inhibition test (Desmodesmus subspicatus). The median effective concentration (EC50) values for the algal inhibition tests were calculated for the end point of growth rate. The toxicity of CIP and NOR to green algae after electrochemical oxidation, remained unchanged, while that of OFL significantly increased. The results presented in this paper contribute to an understanding of the electrochemical oxidation mechanisms of FQs, and highlight the potential environmental risks of FQs after electrochemical oxidation processes.

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

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    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.

  6. Batch culture fermentation of Penicillium chrysogenum and a report on the isolation, purification, identification and antibiotic activity of citrinin

    Digital Repository Service at National Institute of Oceanography (India)

    PrabhaDevi; DeSouza, L.; Kamat, T.; Rodrigues, C.; Naik, C.G.

    is reported to be a broad spectrum antibiotic especially against Gram positive-bacteria. The present study consists report on Gram-positive bacteria, its activity against Gram-negative bacteria and on its antifungal properties. Primarily, citrinin is a...). Previous Fig. 1—Time course of biomass accumulation and citrinin production during growth of Penicillium chrysogenum in PDB medium. Table 1—Antibacterial activity of citrinin Bacterial pathogens Gram stain Streptomycin (100µg.disc-1...

  7. The Antibiotic Resistance ‘Mobilome’: searching for the link between environment and clinic.

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    Julie ePerry

    2013-05-01

    Full Text Available Antibiotic resistance is an ancient problem, owing to the co-evolution of antibiotic-producing and target organisms in the soil and other environments over millennia. The environmental ‘resistome’ is the collection of all genes that directly or indirectly contribute to antibiotic resistance. Many of these resistance determinants originate in antibiotic-producing organisms (where they serve to mediate self-immunity, while others become resistance determinants only when mobilized and over-expressed in non-native hosts (like plasmid-based β-lactamases. The modern environmental resistome is under selective pressure from human activities such as agriculture, which may influence the composition of the local resistome and lead to gene transfer events. Beyond the environment, we are challenged in the clinic by the rise in both frequency and diversity of antibiotic resistant pathogens. We assume that clinical resistance originated in the environment, but few examples of direct gene exchange between the environmental resistome and the clinical resistome have been documented. Strong evidence exists to suggest that clinical aminoglycoside and vancomycin resistance enzymes, the extended-spectrum β-lactamase CTX-M and the quinolone resistance gene Qnr have direct links to the environmental resistome. In this review, we highlight recent advances in our understanding of horizontal gene transfer of antibiotic resistance genes from the environment to the clinic. Improvements in sequencing technologies coupled with functional metagenomic studies have revealed previously underappreciated diversity in the environmental resistome, and also established novel genetic links to the clinic. Understanding mechanisms of gene exchange becomes vital in controlling the future dissemination of antibiotic resistance.

  8. In Vitro Activities of Nisin and Nisin Derivatives Alone and In Combination with Antibiotics against Staphylococcus Biofilms

    Science.gov (United States)

    Field, Des; O’ Connor, Rory; Cotter, Paul D.; Ross, R. Paul; Hill, Colin

    2016-01-01

    The development and spread of pathogenic bacteria that are resistant to the existing catalog of antibiotics is a major public health threat. Biofilms are complex, sessile communities of bacteria embedded in an organic polymer matrix which serve to further enhance antimicrobial resistance. Consequently, novel compounds and innovative methods are urgently required to arrest the proliferation of drug-resistant infections in both nosocomial and community environments. Accordingly, it has been suggested that antimicrobial peptides could be used as novel natural inhibitors that can be used in formulations with synergistically acting antibiotics. Nisin is a member of the lantibiotic family of antimicrobial peptides that exhibit potent antibacterial activity against many Gram-positive bacteria. Recently we have used bioengineering strategies to enhance the activity of nisin against several high profile targets, including multi-drug resistant clinical pathogens such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, staphylococci, and streptococci associated with bovine mastitis. We have also identified nisin derivatives with an enhanced ability to impair biofilm formation and to reduce the density of established biofilms of methicillin resistant S. pseudintermedius. The present study was aimed at evaluating the potential of nisin and nisin derivatives to increase the efficacy of conventional antibiotics and to assess the possibility of killing and/or eradicating biofilm-associated cells of a variety of staphylococcal targets. Growth curve-based comparisons established that combinations of derivatives nisin V + penicillin or nisin I4V + chloramphenicol had an enhanced inhibitory effect against S. aureus SA113 and S. pseudintermedius DSM21284, respectively, compared to the equivalent nisin A + antibiotic combinations or when each antimicrobial was administered alone. Furthermore, the metabolic activity of established biofilms treated with nisin

  9. In vitro activities of nisin and nisin derivatives alone and in combination with antibiotics against Staphylococcus biofilms

    Directory of Open Access Journals (Sweden)

    Des eField

    2016-04-01

    Full Text Available The development and spread of pathogenic bacteria that are resistant to the existing catalogue of antibiotics is a major public health threat. Biofilms are complex, sessile communities of bacteria embedded in an organic polymer matrix which serve to further enhance antimicrobial resistance. Consequently, novel compounds and innovative methods are urgently required to arrest the proliferation of drug-resistant infections in both nosocomial and community environments. Accordingly, it has been suggested that antimicrobial peptides could be used as novel natural inhibitors that can be used in formulations with synergistically-acting antibiotics. Nisin is a member of the lantibiotic family of antimicrobial peptides that exhibit potent antibacterial activity against many Gram-positive bacteria. Recently we have used bioengineering strategies to enhance the activity of nisin against several high profile targets, including multi-drug resistant clinical pathogens such as methicillin-resistant Staphylococcus aureus (MRSA, vancomycin-resistant enterococci (VRE, staphylococci and streptococci associated with bovine mastitis. We have also identified nisin derivatives with an enhanced ability to impair biofilm formation and to reduce the density of established biofilms of methicillin resistant Staphylococcus pseudintermedius (MRSP. The present study was aimed at evaluating the potential of nisin and nisin derivatives to increase the efficacy of conventional antibiotics and to assess the possibility of killing and/or eradicating biofilm-associated cells of a variety of staphylococcal targets. Growth curve-based comparisons established that combinations of derivatives nisin V + penicillin or nisin I4V + chloramphenicol had an enhanced inhibitory effect against S. aureus SA113 and S. pseudintermedius DSM21284 respectively compared to the equivalent nisin A + antibiotic combinations or when each antimicrobial was administered alone. Furthermore, the metabolic

  10. Bactericidal Antibiotics Induce Toxic Metabolic Perturbations that Lead to Cellular Damage

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    Peter Belenky

    2015-11-01

    Full Text Available Understanding how antibiotics impact bacterial metabolism may provide insight into their mechanisms of action and could lead to enhanced therapeutic methodologies. Here, we profiled the metabolome of Escherichia coli after treatment with three different classes of bactericidal antibiotics (β-lactams, aminoglycosides, quinolones. These treatments induced a similar set of metabolic changes after 30 min that then diverged into more distinct profiles at later time points. The most striking changes corresponded to elevated concentrations of central carbon metabolites, active breakdown of the nucleotide pool, reduced lipid levels, and evidence of an elevated redox state. We examined potential end-target consequences of these metabolic perturbations and found that antibiotic-treated cells exhibited cytotoxic changes indicative of oxidative stress, including higher levels of protein carbonylation, malondialdehyde adducts, nucleotide oxidation, and double-strand DNA breaks. This work shows that bactericidal antibiotics induce a complex set of metabolic changes that are correlated with the buildup of toxic metabolic by-products.

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

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    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.

  12. 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

  13. [In vitro antibacterial activity of rokitamycin, a new macrolide antibiotic. Results of a multicenter study].

    Science.gov (United States)

    Soussy, C J; Le Van Thoi, J; Meyran, M; Joly, B; Derlot, E; Morel, C

    1990-05-01

    Minimal inhibitory concentrations (MIC) of rokitamycin (R) were evaluated by agar dilution for 914 bacterial strain isolated in 4 hospitals and classed as a function of susceptibility and resistance to Macrolides-Lincosamides-Streptogramines group (MLS). MICs of R ranged from 0.06 to 1 microgram/ml (mode MIC 0.25-0.5) on Staphylococci susceptible to MLS and on MLSB inducible strains; R was inactive on MLSB constitutive strains. MICs of R ranged from 0.008 to 0.5 microgram/ml (mode MIC 0.06 to 0.25) for Streptococci and Pneumococci susceptible to erythromycin (E) and from 0.06 to greater than 128 for strains resistant to E. Enterococci susceptible to E were inhibited by 0.06 to 0.5 microgram/ml (mode MIC 0.5) and strains resistant to E by 0.25 to greater than 128. Haemophilus were inhibited by 0.5 to 0.65 microgram/ml (mode MICs of R ranged generally from 0.016 to 0.5 microgram/ml (mode MIC 0.12) for C. perfringens and from 0.016 to 1 (mode MIC 0.06) for B. fragilis. Thus, R was shown to be among macrolide antibiotics of resistance strains. Its activity was superior to that of other products of this group spiramycin, josamycin, miokamycin, particularly on Gram positive cocci. R had a good activity on Neisseria, Branhamella, anaerobes and, as others macrolides, was poorly active on Haemophilus.

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

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    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.

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

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    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.

  16. ASSESSMENT OF ANTIMICROBIAL ACTIVITY OF PUNICA GRANATUM AGAINST ANTIBIOTIC-RESISTANT CLOSTRIDIUM PERFRINGENS TYPE (D

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    FRDOOS AL FADEL , SHAZA AL LAHAM, HASSANA CHOUR

    2015-06-01

    Full Text Available The search for new antibiotics and alternative products to solve the increasing number of bacterial resistance to customary antibiotics has become an urgent need. To investigate the effectiveness of the extracts prepared from different parts of Syrian Punica granatum Linn (family Punicaceae, against Clostridium perfringens type (D, which is resistant against many antibiotics, 684 samples were isolated from intestines and livers of death goats by using blood agar, and a selective agar for growing of Clostridium perfringens(SPS agar. The isolated bacteria were typed by using ELISA apparatus. Many parts of Punica granatum was extracted with water, absolute alcohol, then ether by using soxhlet apparatus and rotary evaporator. The Antibiotic susceptibility testing of many antibiotics was conducted by using disc diffusion method in anaerobic atmosphere and break points method. The alcoholic extracts prepared from many parts of punica granatum (pericarp, leaves, flowers, seeds showed different antibacterial effect against Clostridium perfringens type(D,whereas the studied antibiotics had not shown any antibacterial effect, except Clindamycin which showed partial effectiveness. 

  17. 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.

  18. Evolutionary Origin and Conserved Structural Building Blocks of Riboswitches and Ribosomal RNAs: Riboswitches as Probable Target Sites for Aminoglycosides Interaction

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    Elnaz Mehdizadeh Aghdam

    2014-05-01

    Full Text Available Purpose: Riboswitches, as noncoding RNA sequences, control gene expression through direct ligand binding. Sporadic reports on the structural relation of riboswitches with ribosomal RNAs (rRNA, raises an interest in possible similarity between riboswitches and rRNAs evolutionary origins. Since aminoglycoside antibiotics affect microbial cells through binding to functional sites of the bacterial rRNA, finding any conformational and functional relation between riboswitches/rRNAs is utmost important in both of medicinal and basic research. Methods: Analysis of the riboswitches structures were carried out using bioinformatics and computational tools. The possible functional similarity of riboswitches with rRNAs was evaluated based on the affinity of paromomycin antibiotic (targeting “A site” of 16S rRNA to riboswitches via docking method. Results: There was high structural similarity between riboswitches and rRNAs, but not any particular sequence based similarity between them was found. The building blocks including "hairpin loop containing UUU", "peptidyl transferase center conserved hairpin A loop"," helix 45" and "S2 (G8 hairpin" as high identical rRNA motifs were detected in all kinds of riboswitches. Surprisingly, binding energies of paromomycin with different riboswitches are considerably better than the binding energy of paromomycin with “16S rRNA A site”. Therefore the high affinity of paromomycin to bind riboswitches in comparison with rRNA “A site” suggests a new insight about riboswitches as possible targets for aminoglycoside antibiotics. Conclusion: These findings are considered as a possible supporting evidence for evolutionary origin of riboswitches/rRNAs and also their role in the exertion of antibiotics effects to design new drugs based on the concomitant effects via rRNA/riboswitches.

  19. ANTIBACTERIAL ACTIVITY OF SOME WILD MEDICAL PLANTS EXTRACT TO ANTIBIOTIC RESISTANT ESCHERICHIA COLI

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    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

  20. Immunochemical detection of aminoglycosides in milk and kidney

    NARCIS (Netherlands)

    Haasnoot, W.; Stouten, P.; Cazemier, G.; Lommen, A.; Nouws, J.F.M.; Keukens, H.J.

    1999-01-01

    In 1996, the European Union established provisional maximum residue limits (MRL) for gentamicin, neomycin, streptomycin and dihydrostreptomycin in milli and tissue (0.1-5 mg kg-1). For the detection of these four aminoglycosides, three enzyme linked immunosorbent assays (ELISA) for applications in m

  1. Aminoglycosides block the Kv3.1 potassium channel and reduce the ability of inferior colliculus neurons to fire at high frequencies.

    Science.gov (United States)

    Liu, Si-Qiong J; Kaczmarek, Leonard K

    2005-03-01

    The Kv3.1 potassium channel is expressed at high levels in auditory nuclei and contributes to the ability of auditory neurons to fire at high frequencies. We have tested the effects of streptomycin, an agent that produces progressive hearing loss, on the firing properties of inferior colliculus neurons and on Kv3.1 currents in transfected cells. We found that in inferior colliculus neurons, intracellular streptomycin decreased the current density of a high threshold, noninactivating outward current and reduced the rate of repolarization of action potentials and the ability of these neurons to fire at high frequencies. Furthermore, potassium current in CHO cells transfected with the Kv3.1 gene was reduced by 50% when cells were cultured in the presence of streptomycin or when streptomycin was introduced intracellularly in the pipette solution. In the presence of intracellular streptomycin, the activation rate of Kv3.1 current increased and inhibition by extracellular TEA become voltage-dependent. The data indicate that streptomycin inhibits Kv3.1 currents by inducing a conformational change in the Kv3.1 channel. The hearing loss caused by aminoglycoside antibiotics may be partially mediated by their inhibition of Kv3.1 current in auditory neurons.

  2. Polyprenols of Ginkgo biloba Enhance Antibacterial Activity of Five Classes of Antibiotics

    Science.gov (United States)

    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 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. PMID:27642597

  3. 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.

  4. Degradation of ciprofloxacin and sulfamethoxazole by ferrous-activated persulfate: implications for remediation of groundwater contaminated by antibiotics.

    Science.gov (United States)

    Ji, Yuefei; Ferronato, Corinne; Salvador, Arnaud; Yang, Xi; Chovelon, Jean-Marc

    2014-02-15

    The wide occurrence of antibiotics in groundwater raised great scientific interest as well as public awareness in recent years due to their potential ability to spread antibiotic resistant gene and pose risk to humans. The present study investigated the ferrous ion (Fe(II)) activated decomposition of persulfate (S2O8(2-)), as a potential in situ chemical oxidation (ISCO) approach, for remediation of groundwater contaminated by antibiotics. Fe(II)-persulfate mediated ciprofloxacin (CIP) degradation was found to be more efficient than sulfamethoxazole (SMX) at near neutral pH (pH6.0), probably due to the higher electric density in CIP molecule and its ability to form complex with Fe(II) as a ligand. Hydroxyl (HO) and sulfate radical (SO4(-)) were determined to be responsible for the degradation of CIP and SMX in Fe(II)-persulfate system by molecular probes. No enhancement in the degradation of CIP was observed when citrate (CA), ethylenediaminetetraacetate (EDTA) and (S,S)-ethylenediamine-N,N'-disuccinate (EDDS) were used as Fe(II) chelating agents in Fe(II)-persulfate system. For SMX, CA and EDTA accelerated the degradation by Fe(II)-persulfate. Degradation of antibiotics in river water matrix was nearly the same as that in Milli-Q water, implying the possibility of using Fe(II)-persulfate for antibiotics depletion under environmentally relevant condition. A comparison of the degradation efficiency of SMX with other sulfonamides and sulfanilic acid indicated that the heterocyclic ring has a large impact on the degradation of sulfonamides. Transformation products of CIP and SMX by Fe(II)-persulfate were analyzed by solid phase extraction-liquid chromatography-mass spectrometry (SPE-LC-MS) technique. Based on the intermediate products, Fe(II)-persulfate mediated CIP degradation pathways were tentatively proposed.

  5. Comparison of the antibiotic activities of Daptomycin, Vancomycin, and the investigational Fluoroquinolone Delafloxacin against biofilms from Staphylococcus aureus clinical isolates.

    Science.gov (United States)

    Siala, Wafi; Mingeot-Leclercq, Marie-Paule; Tulkens, Paul M; Hallin, Marie; Denis, Olivier; Van Bambeke, Françoise

    2014-11-01

    Biofilm-related infections remain a scourge. In an in vitro model of biofilms using Staphylococcus aureus reference strains, delafloxacin and daptomycin were found to be the most active among the antibiotics from 8 different pharmacological classes (J. Bauer, W. Siala, P. M. Tulkens, and F. Van Bambeke, Antimicrob. Agents Chemother. 57:2726-2737, 2013, doi:10.1128/AAC.00181-13). In this study, we compared delafloxacin to daptomycin and vancomycin using biofilms produced by 7 clinical strains (S. aureus epidemic clones CC5 and CC8) in order to rationalize the differences observed between the antibiotics and strains. The effects of the antibiotics on bacterial viability (resazurin reduction assay) and biomass (crystal violet staining) were measured and correlated with the proportion of polysaccharides in the matrix, the local microenvironmental pH (micro-pH), and the antibiotic penetration in the biofilm. At clinically meaningful concentrations, delafloxacin, daptomycin, and vancomycin caused a ≥25% reduction in viability against the biofilms formed by 5, 4, and 3 strains, respectively. The antibiotic penetration within the biofilms ranged from 0.6 to 52% for delafloxacin, 0.2 to 10% for daptomycin, and 0.2 to 1% for vancomycin; for delafloxacin, this was inversely related to the polysaccharide proportion in the matrix. Six biofilms were acidic, explaining the high potency of delafloxacin (lower MICs at acidic pH). Norspermidine and norspermine (disassembling the biofilm matrix) drastically increased delafloxacin potency and efficacy (50% reduction in viability for 6 biofilms at clinically meaningful concentrations) in direct correlation with its increased penetration within the biofilm, while they only modestly improved daptomycin efficacy (50% reduction in viability for 2 biofilms) and penetration, and they showed marginal effects with vancomycin. Delafloxacin potency and efficacy against biofilms are benefited by its penetration into the matrix and the local

  6. Decay mechanisms of protonated 4-quinolone antibiotics after electrospray ionization and ion activation.

    Science.gov (United States)

    Kovačević, Borislav; Schorr, Pascal; Qi, Yulin; Volmer, Dietrich A

    2014-11-01

    This study presents a detailed experimental investigation of charge isomers of protonated 4-quinolone antibiotics molecules formed during electrospray ionization (ESI) with proposed dissociation mechanisms after collisional activation. Piperazinyl quinolones have been previously shown to exhibit erratic behavior during tandem MS analyses of biological samples, which originated from varying ratios of two isomeric variants formed during ESI. Here, a combination of ESI-collision-induced dissociation (CID), differential ion mobility spectrometry (DMS), high resolution MS, and density functional theory (DFT) was used to investigate the underlying mechanisms of isomer formation and their individual dissociation behaviors. The study focused on ciprofloxacin; major findings were confirmed using structurally related 4-quinolones. DFT calculations showed a reversal of basicity for piperazinyl quinolones between liquid and gas phase. We provide an experimental comparison and theoretical treatment of factors influencing the formation ratio of the charge isomers during ESI, including solvent pH, protic/aprotic nature of solvent, and structural effects such as pK a and proton affinity. The actual dissociation mechanisms of the isomers of the protonated molecules were studied by separating the individual isomers via DMS-MS, which allowed type-specific CID spectra to be recorded. Both primary CID reactions of the two charge isomers originated from the same carboxyl group by charge-remote (CO(2) loss) and charge-mediated (H(2)O loss) fragmentation of the piperazinyl quinolones, depending on whether the proton resides on the more basic keto or the piperazinyl group, followed by a number of secondary dissociation reactions. The proposed mechanisms were supported by calculated energies of precursors, transition states, and products for competing pathways.

  7. Demographics of antibiotic persistence

    DEFF Research Database (Denmark)

    Steiner, Ulrich; Kollerova, Silvia; Jouvet, Lionel

    2016-01-01

    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....

  8. 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.

  9. 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.

  10. Degradation and antibiotic activity reduction of chloramphenicol in aqueous solution by UV/H2O2 process.

    Science.gov (United States)

    Zuorro, Antonio; Fidaleo, Marco; Fidaleo, Marcello; Lavecchia, Roberto

    2014-01-15

    The efficacy of the UV/H2O2 process to degrade the antibiotic chloramphenicol (CHL) was investigated at 20 °C using a low-pressure mercury lamp as UV source. A preliminary analysis of CHL degradation showed that the process followed apparent first-order kinetics and that an optimum H2O2 concentration existed for the degradation rate. The first-order rate constant was used as the response variable and its dependence on initial CHL and H2O2 concentrations, UV light intensity and reaction time was investigated by a central composite design based on the response surface methodology. Analysis of response surface plots revealed a large positive effect of radiation intensity, a negative effect of CHL concentration and that there was a region of H2O2 concentration leading to maximum CHL degradation. CHL solutions submitted to the UV/H2O2 process were characterized by TOC and their activity against Escherichia coli and Staphylococcus aureus was assessed. No residual antibiotic activity was detected, even at CHL concentrations higher than those used in the designed experiments. Overall, the obtained results strongly support the possibility of reducing the risks associated with the release of CHL into the environment, including the spread of antibiotic resistance, by the UV/H2O2 process.

  11. Effectiveness of antibiotic combination therapy as evaluated by the Break-point Checkerboard Plate method for multidrug-resistant Pseudomonas aeruginosa in clinical use.

    Science.gov (United States)

    Nakamura, Itaru; Yamaguchi, Tetsuo; Tsukimori, Ayaka; Sato, Akihiro; Fukushima, Shinji; Mizuno, Yasutaka; Matsumoto, Tetsuya

    2014-04-01

    Multidrug-resistant Pseudomonas aeruginosa (MDRP) strains are defined as having resistance to the following 3 groups of antibiotics: carbapenems, aminoglycosides, and fluoroquinolones. Antibiotic combinations have demonstrated increased activity in vitro compared with a single agent. As an in vitro method of determining the combination activity of antibiotics, the Break-point Checkerboard Plate (BC-plate) can be used routinely in clinical microbiology laboratories. We evaluated the effectiveness of the BC-plate for MDRP infections in clinical settings. We retrospectively selected cases of MDRP infection treated with combination therapy of antibiotics in Tokyo Medical University Hospital (1015 beds), Tokyo, Japan, from November 2010 to October 2012. A total of 28 MDRP strains were clinically isolated from 28 patients during the study period. This study design is a case series of MDRP infection. Six infections among the 28 patients were treated based on the results of the BC-plate assay, and the 6 strains tested positive for MBL. One patient had pneumonia, 3 had urinary tract infections, 1 had vertebral osteomyelitis, and 1 had nasal abscess. The combination of aztreonam with amikacin demonstrated the most frequently recognized in vitro effect (5 patients). Next, aztreonam with ciprofloxacin and piperacillin with amikacin revealed equivalent in vitro effects (3 patients, respectively). The clinical cure rate was 83.3% (5/6 patients). Antibiotic combination therapy based on the results of the BC-plate assay might indicate the effective therapy against MDRP infection in clinical settings.

  12. Compatibility and anticoccidial activity of lasalocid in combination with roxarsone and antibiotics against Eimeria mixed infection in chicks.

    Science.gov (United States)

    Schildknecht, E G; Trainor, C; Givens, S V; De Young, W W; Mitrovic, M

    1980-02-01

    Lasalocid at the concentration of .0075% (68 g/ton) with and without roxarsone 45.4 g/ton was fed in combination with the growth promotants bacitracin methylene disalicylate 200 g/ton, bambermycins 2 g/ton, lincomycin 4 g/ton, nosiheptide 2.5 g/ton, zinc bacitracin 200 g/ton g/ton, and virginiamycin 20 g/ton exhibited a high degree of anticoccidial activity against mixed Eimeria infection in chickens in 9 day challenged battery trials. In these short term challenge trials chicks fed lasalocid, and the lasalocid growth promotant combinations, performed significantly better (P roxarsone-antibiotic combinations allowed for numerical increases in gains, improvement in feed conversion, and numerical decreases in lesions (in some cases, statistically significant (P roxarsone was combined with the antibiotics, the combination resulted in numerically improved performance, reduced mortality, and in most instances, statistically significant decreases in lesions (P .05) over the infected, unmedicated control.

  13. 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…

  14. 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 ...

  15. 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....

  16. In Vitro Antibiotic Susceptibilities of Yersinia pestis Determined by Broth Microdilution following CLSI Methods

    OpenAIRE

    2015-01-01

    In vitro susceptibilities to 45 antibiotics were determined for 30 genetically and geographically diverse strains of Yersinia pestis by the broth microdilution method at two temperatures, 28°C and 35°C, following Clinical and Laboratory Standards Institute (CLSI) methods. The Y. pestis strains demonstrated susceptibility to aminoglycosides, quinolones, tetracyclines, β-lactams, cephalosporins, and carbapenems. Only a 1-well shift was observed for the majority of antibiotics between the two te...

  17. 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.

  18. Validated spectrofluorimetric method for determination of selected aminoglycosides

    Science.gov (United States)

    Omar, Mahmoud A.; Ahmed, Hytham M.; Hammad, Mohamed A.; Derayea, Sayed M.

    2015-01-01

    New, sensitive, and selective spectrofluorimetric method was developed for determination of three aminoglycoside drugs in different dosage forms, namely; neomycin sulfate (NEO), tobramycin (TOB) and kanamycin sulfate (KAN). The method is based on Hantzsch condensation reaction between the primary amino group of aminoglycosides with acetylacetone and formaldehyde in pH 2.7 yielding highly yellow fluorescent derivatives measured emission (471 nm) and excitation (410 nm) wavelengths. The fluorescence intensity was directly proportional to the concentration over the range 10-60, 40-100 and 5-50 ng/mL for NEO, TOB and KAN respectively. The proposed method was applied successfully for determination of these drugs in their pharmaceutical dosage forms.

  19. 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.

  20. 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.

  1. Possible postsynaptic action of aminoglycosides in the frog rectus abdominis.

    Directory of Open Access Journals (Sweden)

    Karataş Y

    2000-04-01

    Full Text Available The present study was undertaken to investigate the postsynaptic effects of aminoglycosides on contractions evoked by acetylcholine (ACh, KCl, electrical field stimulation (EFS and Na(+- and Ca(2+-free Ringer solution with 0.2 mM Na2 EDTA (NaFCaFR in the isolated frog rectus abdominis. Neomycin inhibited contraction elicited by ACh, NaFCaFR, and EFS at the higher frequencies (8 and 10 Hz but not those elicited by KCl and EFS at the lower frequencies (2, 3 and 5 Hz. D-tubocurarine inhibited ACh-induced contractions in a concentration-dependent manner. In addition, drug reduced EFS-evoked contractions to a limited extent. Lower concentrations (10(-5, 5 x 10(-5, 10(-4, 2 x 10(-4 and 3 x 10(-4 M but not higher concentrations (4 x 10(-4 and 5 x 10(-4 M of methoxyverapamil exhibited a concentration-dependent inhibitory action on NaFCaFR-induced contractions. Similar inhibitions of the same type of contraction were displayed by aminoglycosides (neomycin, streptomycin, netilmycin, gentamycin and amikacin. These results suggest that in addition to their antagonistic action on nicotinic receptors in the frog rectus abdominis, aminoglycosides may exert stabilizing effects on some functional components contributing to contractions at the membrane.

  2. COMBINATIONAL ADMINISTRATION OF AMINOGLYCOSIDES AND LOOP DIURETICS AS AN EFFICIENT STRATEGY TO ESTABLISH DEAFNESS MODELS IN RATS

    Institute of Scientific and Technical Information of China (English)

    CONG Tao; LIU Riyuan; YUAN Shuolong; XU Liangwei; YANG Shiming

    2014-01-01

    It is known that aminoglycoside antibiotics can damage the vestibular and auditory sensory epithelia, and the loop diuretics can enhance the ototoxic effect of aminoglycosides. Previous studies on the synergistic effect of these two types of drugs have used mice, guinea pigs and cats, but not rats. The aim of this study was to determine this synergistic effects in rat cochleae. Rats received intravenous injections of different doses of furosemide and/or intramuscular injections of kanamycin sulfate. Au-ditory brainstem response (ABR), scanning electron microscopy (SEM) and immunocytochemistry were used to determine the effects of drug administration. In the group receiving combined administration of furosemide and kanamycin, the ABR thresh-old showed significant elevation 3 days after drug administration, greater than single drug administration. The hair cells showed various degrees of injury from the apical turn to the basal turn of the cochlea and from the outer hair cells to the inner hair cells. Neuron fibers of the hair cells showed significant loss 7 days after the drug administration, but the number of spiral ganglia did not decrease and supporting cells showed no signs of injury. Our study suggest that combined administration of fu-rosemide and kanamycin has an synergistic ototoxic effect, and can result in hair cell loss and hearing loss in rats.

  3. Phytochemical Analysis and Modulation of Antibiotic Activity by Luehea paniculata Mart. & Zucc. (Malvaceae) in Multiresistant Clinical Isolates of Candida Spp.

    Science.gov (United States)

    Calixto Júnior, João T.; Morais, Selene M.; Martins, Clécio G.; Vieira, Larissa G.; Morais-Braga, Maria Flaviana B.; Carneiro, Joara N. P.; Machado, Antonio J. P.; Menezes, Irwin R. A.; Tintino, Saulo R.; Coutinho, Henrique D. M.

    2015-01-01

    The high incidence of fungal infections has led to the continuous search for new drugs. Extracts of Luehea paniculata, a tree of multiple medicinal uses, were evaluated for anti-Candida activity, as well as its modulator potential of the Fluconazole antibiotic. Chemical prospecting of ethanol extracts of leaf and bark was carried out, the quantification of total phenols and flavonoids, characterized by the HPLC-DAD technique. The rosmarinic acid and the vitexin flavonoid were observed as major constituents in ELELP and ESWELP, respectively. Antioxidant activity was also evaluated by the method of scavenging the free radical DPPH, and quercetin was used as standard, obtaining IC50 values: 0.341 (mg/mL) for ELELP and 0.235 (mg/mL) for ESWELP. The microdilution assay was performed for antifungal activity against strains of Candida albicans, C. krusei, and C. tropicalis and showed minimum inhibitory concentrations values ≥1024 μg/mL. In the modulator action of extracts on Fluconazole against multiresistant clinical isolates of Candida (subinhibitory concentration minimum of 128 μg/mL), a significant synergism was observed, indicating that the extracts potentiated the antifungal effect against C. tropicalis, where antioxidant flavonoids could be responsible. This is the first report about modifying activity of the antibiotic action of a species of the genus Luehea. PMID:25821822

  4. Phytochemical analysis and modulation of antibiotic activity by Luehea paniculata Mart. & Zucc. (Malvaceae) in multiresistant clinical isolates of Candida spp.

    Science.gov (United States)

    Calixto Júnior, João T; Morais, Selene M; Martins, Clécio G; Vieira, Larissa G; Morais-Braga, Maria Flaviana B; Carneiro, Joara N P; Machado, Antonio J P; Menezes, Irwin R A; Tintino, Saulo R; Coutinho, Henrique D M

    2015-01-01

    The high incidence of fungal infections has led to the continuous search for new drugs. Extracts of Luehea paniculata, a tree of multiple medicinal uses, were evaluated for anti-Candida activity, as well as its modulator potential of the Fluconazole antibiotic. Chemical prospecting of ethanol extracts of leaf and bark was carried out, the quantification of total phenols and flavonoids, characterized by the HPLC-DAD technique. The rosmarinic acid and the vitexin flavonoid were observed as major constituents in ELELP and ESWELP, respectively. Antioxidant activity was also evaluated by the method of scavenging the free radical DPPH, and quercetin was used as standard, obtaining IC50 values: 0.341 (mg/mL) for ELELP and 0.235 (mg/mL) for ESWELP. The microdilution assay was performed for antifungal activity against strains of Candida albicans, C. krusei, and C. tropicalis and showed minimum inhibitory concentrations values ≥1024 μg/mL. In the modulator action of extracts on Fluconazole against multiresistant clinical isolates of Candida (subinhibitory concentration minimum of 128 μg/mL), a significant synergism was observed, indicating that the extracts potentiated the antifungal effect against C. tropicalis, where antioxidant flavonoids could be responsible. This is the first report about modifying activity of the antibiotic action of a species of the genus Luehea.

  5. Cymbopogon citratus protects against the renal injury induced by toxic doses of aminoglycosides in rabbits

    Directory of Open Access Journals (Sweden)

    N Ullah

    2013-01-01

    Full Text Available Renal injury is the most common side-effect of aminoglycosides. These antimicrobial drugs are particularly effective against Gram-negative microorganisms. The present study was conducted to investigate the renal protective activity of Cymbopogon citratus in gentamicin-induced nephrotoxicity. Male rabbits were divided into four groups (n=6 including group 1 (0.9% saline treated, group 2 (80 mg/kg/day gentamicin-treated, group 3 (200 mg/kg/day Cymbopogon citratus treated and group 4 (80 mg/kg/day gentamicin and 200 mg/kg/day Cymbopogon citratus treated. Biochemical kidney functioning parameters, urinary enzymes and histopathological examination were performed. The results of the present study showed that simultaneous administration of Cymbopogon citrates and gentamicin significantly protected alteration in body weight, blood urea nitrogen, serum creatinine, creatinine clearance, serum uric acid, serum electrolytes, urinary volume, urinary protein, urinary lactate dehydrogenase and urinary alkaline phosphatase induced by gentamicin. Histological examination of the kidney also suggested the same. It is concluded from the current study that co-administration of Cymbopogon citratus with gentamicin for 3 weeks successfully prevented renal damage associated with aminoglycosides.

  6. Intrinsic resistance to aminoglycosides in Enterococcus faecium is conferred by the 16S rRNA m5C1404-specific methyltransferase EfmM

    DEFF Research Database (Denmark)

    Galimand, Marc; Schmitt, Emmanuelle; Panvert, Michel;

    2011-01-01

    confers resistance to these drugs. The EfmM protein shows significant sequence similarity to E. coli RsmF (previously called YebU), which is a 5-methylcytidine (m(5)C) methyltransferase modifying 16S rRNA nucleotide C1407. The target for EfmM is shown by mass spectrometry to be a neighboring 16S r......RNA nucleotide at C1404. EfmM uses the methyl group donor S-adenosyl-L-methionine to catalyze formation of m(5)C1404 on the 30S ribosomal subunit, whereas naked 16S rRNA and the 70S ribosome are not substrates. Addition of the 5-methyl to C1404 sterically hinders aminoglycoside binding. Crystallographic......Aminoglycosides are ribosome-targeting antibiotics and a major drug group of choice in the treatment of serious enterococcal infections. Here we show that aminoglycoside resistance in Enterococcus faecium strain CIP 54-32 is conferred by the chromosomal gene efmM, encoding the E. faecium...

  7. 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.

  8. 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

  9. 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.

  10. 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.

  11. Modulation of the Antibiotic Activity by Extracts from Amburana cearensis A. C. Smith and Anadenanthera macrocarpa (Benth. Brenan

    Directory of Open Access Journals (Sweden)

    Fernando G. Figueredo

    2013-01-01

    Full Text Available The aim of this study was to verify the possible interactions between ethanol extracts of Amburana cearensis A. C. Smith and Anadenanthera macrocarpa (Benth. Brenan, combined with six antimicrobial drugs against multiresistant strains of Staphylococcus aureus and Escherichia coli isolated from humans. The antibacterial activity of the extracts was determined using the minimum inhibitory concentration (MIC. The microdilution assay was performed to verify the interactions between the natural products and the antibiotics using a subinhibitory concentration. The activity of amikacin associated with the extract of Anadenanthera macrocarpa against EC 27 was enhanced, demonstrating an MIC reduction from 128 to 4 μg/mL. Among the β-lactams, no potentiation on its activity was observed, with exception to the antagonism of the natural products with ampicillin against S. aureus 358.

  12. Electrophoretic deposition of CdS coatings and their photocatalytic activities in the degradation of tetracycline antibiotic

    Science.gov (United States)

    Vázquez, A.; Hernández-Uresti, D. B.; Obregón, S.

    2016-11-01

    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.

  13. The bactericidal activity of β-lactam antibiotics is increased by metabolizable sugar species

    DEFF Research Database (Denmark)

    Thorsing, Mette; Bentin, Thomas; Givskov, Michael;

    2015-01-01

    Here, the influence of metabolizable sugars on the susceptibility of Escherichia coli to β-lactam antibiotics was investigated. Notably, monitoring growth and survival of mono- and combination-treated planktonic cultures showed a 1000- to 10 000-fold higher antibacterial efficacy of carbenicillin...... and cefuroxime in the presence of certain sugars, whereas other metabolites had no effect on β-lactam sensitivity. This effect was unrelated to changes in growth rate. Light microscopy and flow cytometry profiling revealed that bacterial filaments, formed due to β-lactam-mediated inhibition of cell division......, rapidly appeared upon β-lactam mono-treatment and remained stable for up to 18 h. The presence of metabolizable sugars in the medium did not change the rate of filamentation, but led to lysis of the filaments within a few hours. No lysis occurred in E. coli mutants unable to metabolize the sugars, thus...

  14. 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.

  15. 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.

  16. 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.

  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. Multiple antibiotic sensitivity in a pediatric population.

    Science.gov (United States)

    Kamada, M M; Twarog, F; Leung, D Y

    1991-01-01

    Multiple antibiotic sensitivity (MAS), a common but complex clinical problem, has not been reviewed in the pediatric population. We evaluated 120 children with a history of MAS. The offending antibiotics were beta lactam (186 adverse reactions), sulfonamide (86 adverse reactions), macrolide (32 adverse reactions), erythromycin/sulfisoxazole (26 adverse reactions), aminoglycoside (2 adverse reactions), and tetracycline (2 adverse reactions). Urticaria occurred in 183 reactions, followed by polymorphous rash (n = 71), angioedema (n = 19), erythema multiform (n = 9), bronchospasm (n = 8), arthralgia (n = 7), serum sickness (n = 4), and laryngeal edema (n = 3), the mean age for the first reaction was 3 years (range 1 month to 13 years). Adverse reaction to three classes of antibiotics were noted in 22 patients, and two patients were noted to have adverse reactions to four or more antibiotic classes. Skin tests (ST) were performed in 98 children using penicillin G, a commercial benzyl penicilloyl polylysine, a minor determinant mixture, and a beta lactam analog. Positive ST were noted in 26% (31/120) of the MAS patients. Children with a history of MAS are likely to have true IgE-mediated reactions as documented by positive immediate hypersensitivity reactions to penicillin and/or its minor determinants. Therefore, MAS patients should be carefully evaluated for antibiotic sensitivity and not be assumed to have sensitivity to drug formulation as a basis for MAS.

  19. Hearing loss and nephrotoxicity treatment in patients with in long-term aminoglycoside tuberculosis

    NARCIS (Netherlands)

    van Altena, R

    2002-01-01

    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 fre

  20. Spectrophotometric Determination of Aminoglycoside Antibiotics Based on their Oxidation by Potassium Permanganate

    Energy Technology Data Exchange (ETDEWEB)

    El-Didamony, A. M.; Ghoneim, A. K.; Telebany, A. M. [Zagazig University, Zagazig (Egypt); Amin, A. S. [Banha University, Banha (Egypt)

    2006-08-15

    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{sub 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{sup -1} for neomycin and streptomycin, respectively. The apparent molar absorptivity and sandell sensitivity values are in the range 5.47-6.20x10{sup 4}, 2.35-2.91x10{sup 5} L mol{sup -1} cm{sup -1} and 7.57-8.59, 5.01-6.2 ng cm{sup -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.

  1. Quantifying the associations between antibiotic exposure and resistance - a step towards personalised antibiograms.

    Science.gov (United States)

    Sanden, L; Paul, M; Leibovici, L; Andreassen, S

    2016-12-01

    Empirical antibiotic treatment is selected to target causative bacteria with antibiotics to which they are not resistant. We analysed the increase in bacterial resistance among individual patients associated with antibiotic exposure in the month prior to infection onset, compared to unexposed patients. From a series of prospective cohort studies in the period 2002-2011 at Beilinson Hospital, Israel, 4232 consecutive patients suspected of infection were included. We analysed resistance to antibiotics in bacterial isolates from patients with clinically significant and microbiologically documented infections, starting antibiotics after obtaining cultures (n = 775). In Gram-negative bacteria, significantly higher rates of resistance was associated with exposure to antibiotics, while no significant associations were found for Gram-positive bacteria. Significant odds ratios (ORs) for increased resistance to classes of antibiotics ranged from 2.1 to 3.3 in Gram-negative bacteria from patients exposed to any antibiotic(s), with quinolones having the highest OR, followed by aminoglycosides, penicillins with β-lactamase inhibitor and cephalosporins. The majority of significant associations also had significant ORs after exposure to another class of antibiotics, indicating a substantial effect of cross-resistance. In conclusion, increased resistance was observed following exposure to antibiotics, both from the same class and from other classes. The results indicate a reason to adjust the expected coverage of empirical antibiotic treatments for patients recently exposed to antibiotics, with some antibiotics being more affected than others.

  2. 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.

  3. Selective antimicrobial activity and mode of action of adepantins, glycine-rich peptide antibiotics based on anuran antimicrobial peptide sequences.

    Science.gov (United States)

    Ilić, Nada; Novković, Mario; Guida, Filomena; Xhindoli, Daniela; Benincasa, Monica; Tossi, Alessandro; Juretić, Davor

    2013-03-01

    A challenge when designing membrane-active peptide antibiotics with therapeutic potential is how to ensure a useful antibacterial activity whilst avoiding unacceptable cytotoxicity for host cells. Understanding their mode of interaction with membranes and the reasons underlying their ability to distinguish between bacterial and eukaryotic cytoplasmic cells is crucial for any rational attempt to improve this selectivity. We have approached this problem by analysing natural helical antimicrobial peptides of anuran origin, using a structure-activity database to determine an antimicrobial selectivity index (SI) relating the minimal inhibitory concentration against Escherichia coli to the haemolytic activity (SI=HC(50)/MIC). A parameter that correlated strongly with SI, derived from the lengthwise asymmetry of the peptides' hydrophobicity (sequence moment), was then used in the "Designer" algorithm to propose novel, highly selective peptides. Amongst these are the 'adepantins', peptides rich in glycines and lysines that are highly selective for Gram-negative bacteria, have an exceptionally low haemolytic activity, and are less than 50% homologous to any other natural or synthetic antimicrobial peptide. In particular, they showed a very high SI for E. coli (up to 400) whilst maintaining an antimicrobial activity in the 0.5-4μM range. Experiments with monomeric, dimeric and fluorescently labelled versions of the adepantins, using different bacterial strains, host cells and model membrane systems provided insight into their mechanism of action.

  4. Rapid and liquid-based selection of genetic switches using nucleoside kinase fused with aminoglycoside phosphotransferase.

    Directory of Open Access Journals (Sweden)

    Masahiro Tominaga

    Full Text Available The evolutionary design of genetic switches and circuits requires iterative rounds of positive (ON- and negative (OFF- selection. We previously reported a rapid OFF selection system based on the kinase activity of herpes simplex virus thymidine kinase (hsvTK on the artificial mutator nucleoside dP. By fusing hsvTK with the kanamycin resistance marker aminoglycoside-(3'-phosphotransferase (APH, we established a novel selector system for genetic switches. Due to the bactericidal nature of kanamycin and nucleoside-based lethal mutagenesis, both positive and negative selection could be completed within several hours. Using this new selector system, we isolated a series of homoserine lactone-inducible genetic switches with different expression efficiencies from libraries of the Vibrio fischeri lux promoter in two days, using only liquid handling.

  5. Development of antibiotic resistance in Pseudomonas aeruginosa during two decades of antipseudomonal treatment at the Danish CF Center

    DEFF Research Database (Denmark)

    Ciofu, O; Giwercman, B; Pedersen, S S

    1994-01-01

    was found between the MIC and the number of antipseudomonal courses of antibiotics. The proportion of resistant in vivo selected P. aeruginosa strains, presumed to be stably derepressed producers of chromosomal beta-lactamase, also increased significantly during the period studied. Our results confirm...... that the beta-lactamase production is an important mechanism of antibiotic resistance in P. aeruginosa.......At the Danish CF Center patients with chronic Pseudomonas aeruginosa lung infection were treated 3-4 times a year (from 1976) with a 2-week intravenous antipseudomonal course which included preferentially an aminoglycoside and a beta-lactam antibiotic. We investigated the development of antibiotic...

  6. 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.

  7. 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.

  8. 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.

  9. 3 Certain Shell Hospital Inpatient Antibiotic Uses are Analysed%某三甲医院住院病人抗生素利用分析

    Institute of Scientific and Technical Information of China (English)

    刘伟卿

    2002-01-01

    Objective We appraise the application condition of 3 certain shell hospital antibiotics. Methods According to medicine, we use research method. As the 280 certain courtyard regular inpatients of May 2001 use the condition of antibiotic,investigate. With the survey that DDD studies as medicine use, we worth. Is judgement doctor with DUI reasonable use the standard of medicine? Results 185 examples are used antibiotic, take 66.07%. With penicillins, Quinolones and Aminoglycosides use count frequently highest. Before locating in, 5 antibiotics are in proper order. Penicillin G, Clindamycin,Amikacin, Sodium Cefotaxime, and Ciprofloxacin. Conclusions The most antibiotic DUI ≤ 1, whole, the application ofantibiotic is reasonable.

  10. Staphylococcus aureus Alters Growth Activity, Autolysis, and Antibiotic Tolerance in a Human Host-Adapted Pseudomonas aeruginosa Lineage

    DEFF Research Database (Denmark)

    Frydenlund Michelsen, Charlotte; Christensen, Anne-Mette; Bojer, Martin Saxtorph

    2014-01-01

    Interactions among members of polymicrobial infections or between pathogens and the commensal flora may determine disease outcomes. Pseudomonas aeruginosa and Staphylococcus aureus are important opportunistic human pathogens and are both part of the polymicrobial infection communities in human....... aeruginosa DK2 strains outcompeted S. aureus during coculture on agar plates, we found that later P. aeruginosa DK2 strains showed a commensal-like interaction, where S. aureus was not inhibited by P. aeruginosa and the growth activity of P. aeruginosa was enhanced in the presence of S. aureus. This effect...... is mediated by one or more extracellular S. aureus proteins greater than 10 kDa, which also suppressed P. aeruginosa autolysis and prevented killing by clinically relevant antibiotics through promoting small-colony variant (SCV) formation. The commensal interaction was abolished with S. aureus strains mutated...

  11. 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.

  12. Comparative study of antibacterial activity of wood-decay fungi and antibiotics

    OpenAIRE

    A. F. Md. Hassan Iftekhar; Zubaida Khatoon Choudhry; Md. Ismail Khan; Ahmed Abu Saleh

    2011-01-01

    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.

  13. 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.

  14. 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

  15. 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

    Full Text Available BACKGROUND: 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. METHODS AND FINDINGS: 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. CONCLUSION: Analysis of associations

  16. 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.

  17. Imipenem-cilastatin sodium, a broad-spectrum carbapenem antibiotic combination.

    Science.gov (United States)

    Pastel, D A

    1986-09-01

    The chemistry, antimicrobial spectrum, mechanism of action, pharmacology and pharmacokinetics, clinical use, adverse effects, dosage and administration, place in therapy, cost-effectiveness, and formulary considerations of imipenem-cilastatin sodium are reviewed. Imipenem is the first carbapenem antibiotic of the thienamycin class to be used clinically. Imipenem has the widest spectrum of antimicrobial activity of currently available beta-lactam agents and, in contrast to other beta-lactam antibiotics, lacks cross resistance with recently introduced extended-spectrum penicillins and third-generation cephalosporins. Against gram-positive and gram-negative aerobic and anaerobic organisms, imipenem demonstrates excellent activity. Pseudomonas maltophilia, some strains of Pseudomonas cepacia, and Streptococcus faecium are resistant. Strains of methicillin-resistant staphylococci should also be considered resistant to imipenem. For clinical use imipenem is coadministered in equal parts with cilastatin. Cilastatin is a renal dehydropeptidase inhibitor that inhibits the metabolism of imipenem by renal brush-border enzymes, thus increasing imipenem concentrations in urine. Imipenem-cilastatin is administered by the intravenous route only. The adverse reaction profile of imipenem-cilastatin is similar to t that of other beta-lactam antibiotics. Recommended dosage reductions appropriate for renal impairment should be guided by periodic assessments of renal function, with close adherence to recommended dosage schedules, particularly among patients who are predisposed to seizures or receiving anticonvulsant medication. Imipenem-cilastatin performed well in both comparative and noncomparative trials of clinical efficacy and safety. For infections with multiple organisms (e.g., pelvic, intra-abdominal, or soft-tissue infections), imipenem-cilastatin may be a cost-effective and less toxic single-agent alternative to "standard" combination (e.g., aminoglycoside-penicillin plus an

  18. EF-Tu from the enacyloxin producing Frateuria W-315 strain: Structure/activity relationship and antibiotic resistance.

    Science.gov (United States)

    Créchet, Jean-Bernard; Malosse, Christian; Hountondji, Codjo

    2016-08-01

    In this report, we have demonstrated that the poly(U)-dependent poly(Phe) synthesis activity of elongator factor Tu (EF-Tu) from the enacyloxin producing strain Frateuria sp. W-315 is inhibited by the antibiotic similarly to that of Escherichia coli EF-Tu. The inhibitory effect of enacyloxin observed in a purified system was the same as that obtained with an S30 extract from E. coli or Frateuria sp. W-315, respectively, suggesting that antibiotic resistance of enacyloxin producing Frateuria sp. W-315 is not due neither to EF-Tu nor to other components of the translation machinery but to a still unknown mechanism. The EF-Tu gene, as PCR amplified from Frateuria W-315 genomic DNA and sequenced represented an ORF of 1191 nucleotides corresponding to 396 amino acids. This protein is larger than the product of tufA from E. coli by only two amino acid residues. Alignment of the amino acid sequence of EF-Tu from E. coli with those of Frateuria and Ralstonia solanacearum indicates on average 80% identical amino acid residues and 9.7% conservative replacements between EF-Tu Frateuria and EF-Tu E. coli, on one hand, and 97% identity and 1.7% conservative replacement between EF-Tu Frateuria and EF-Tu Ralstonia solanacearum, on the other hand. These strong primary structure similarities between EF-Tu from different origins are consistent with the fact that this factor is essential for the translation process in all kingdoms of life. Comparison of the effects of antibiotics on EF-Tu Frateuria and EF-Tu E. coli revealed that enacyloxin, kirromycin and pulvomycin exert a stronger stimulation of the GDP dissociation rate on EF-Tu Frateuria, while the effects of the antibiotics on the GDP association rate were comparable for the two EF-Tu species. Different mutants of EF-Tu E. coli were constructed with the help of site directed mutagenesis by changing one or several residues of EF-Tu E. coli by the corresponding residues of EF-Tu Frateuria. The single A45K substitution did

  19. Risk Analysis of Antibiotic Resistance, Berlin, BfR, 10-12 November 2003: activities of the Codex Alimentarius Commission related to antibiotic resistance.

    Science.gov (United States)

    Doyran, S H

    2004-01-01

    The FAO/WHO Codex Alimentarius Commission develops recommendations concerning risk management related to regulatory issues, on the basis of scientific advice provided by FAO and WHO. The complex question of anti-microbial resistance that requires a multidisciplinary approach, has been considered from different point of views in the framework of Codex, especially food hygiene and veterinary drugs and to a lesser extent, plant protection. Antibiotic resistance was considered from the perspective of the food chain and a risk profile was developed. Risk management options were also considered and may be grouped in two main categories: prevention of contamination through the food chain; and prudent use of anti-microbials. It is recognized that further scientific advice is necessary before developing specific risk management options in the framework of Codex. It is expected that the results of the FAO/OIE/WHO Expert Consultations on anti-microbial resistance will provide the necessary guidance for further action.

  20. Structure-activity relationships in aminosterol antibiotics: the effect of stereochemistry at the 7-OH group.

    Science.gov (United States)

    Tessema, Tsemre-Dingel; Gassler, Frank; Shu, Youheng; Jones, Stephen; Selinsky, Barry S

    2013-06-01

    Squalamine and three aminosterol analogs have been shown to inhibit bacterial cell growth and induce lysis of large unilamellar phospholipid vesicles. The analogs differ in the identity of the polyamine attached at C3 of the sterol, and the stereochemistry of a hydroxyl substituent at C7. Analogs with a tetraammonium spermine polyamine are somewhat more active than analogs with a shorter trisammonium spermidine polyamine, and analogs with an axial (α) hydroxyl substituent at C7 are more active than analogs with the corresponding equatorial (β) hydroxyl group. There is some variability noted; the 7β-OH spermine analog is the most active compound against Escherichia coli, but the least effective against Pseudomonas aeruginosa. Lytic activity correlates well with antimicrobial activity of the compounds, but the lytic activity varies with the phospholipid composition of the vesicles.

  1. 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, OP; 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

  2. 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...

  3. Transcriptional regulation of the redD transcriptional activator gene accounts for growth-phase-dependent production of the antibiotic undecylprodigiosin in Streptomyces coelicolor A3(2)

    NARCIS (Netherlands)

    Takano, E.; Gramajo, H.C.; Strauch, E.; White, J.; Bibb, M.J.

    1992-01-01

    Transcription of redD, the activator gene required for production of the red-pigmented antibiotic undecylprodigiosin by Streptomyces coelicolor A3(2), showed a dramatic increase during the transition from exponential to stationary phase. The increase in redD expression was followed by transcription

  4. Artesunate has its enhancement on antibacterial activity of β-lactams via increasing the antibiotic accumulation within methicillin-resistant Staphylococcus aureus (MRSA).

    Science.gov (United States)

    Jiang, Weiwei; Li, Bin; Zheng, Xinchuan; Liu, Xin; Pan, Xichun; Qing, Rongxin; Cen, Yanyan; Zheng, Jiang; Zhou, Hong

    2013-06-01

    Methicillin-resistant Staphylococcus aureus (MRSA) has now emerged as a predominant and serious pathogen because of its resistance to a large group of antibiotics, leading to high morbidity and mortality. Therefore, to develop new agents against resistance is urgently required. Previously, artesunate (AS) was found to enhance the antibacterial effect of β-lactams against MRSA. In this study, AS was first found to increase the accumulation of antibiotics (daunorubicin and oxacillin) within MRSA by laser confocal microscopy and liquid chromatography-tandem MS method, suggesting the increased antibiotics accumulation might be related to the enhancement of AS on antibiotics. Furthermore, AS was found not to destroy the cell structure of MRSA by transmission electron microscope. AS was found to inhibit gene expressions of important efflux pumps such as NorA, NorB and NorC, but not MepA, SepA and MdeA. In conclusion, our results showed that AS was capable of enhancing the antibacterial activity of β-lactams via increasing antibiotic accumulations within MRSA through inhibiting gene expressions of efflux pumps such as NorA, NorB and NorC, but did not destroy the cell structure of MRSA. AS could be further investigated as a candidate drug for treatment of MRSA infection.

  5. 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

  6. Specific antibiotics and nematode trophic groups agree in assessing fungal:bacterial activity in agricultural soil

    DEFF Research Database (Denmark)

    Christensen, S; Dam, M; Vestergaard, M;

    2012-01-01

    There are no methods at hand with a long and proven record for assessing the relative contribution of fungi and bacteria to decomposer activity in soil. Whereas a multitude of methods to determine fungal and bacterial biomass are available, activity assays traditionally relied on the substrate...

  7. 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.

  8. Aminoglycoside-induced hair cell death of inner ear organs causes functional deficits in adult zebrafish (Danio rerio.

    Directory of Open Access Journals (Sweden)

    Phillip M Uribe

    Full Text Available Aminoglycoside antibiotics, like gentamicin, kill inner ear sensory hair cells in a variety of species including chickens, mice, and humans. The zebrafish (Danio rerio has been used to study hair cell cytotoxicity in the lateral line organs of larval and adult animals. Little is known about whether aminoglycosides kill the hair cells within the inner ear of adult zebrafish. We report here the ototoxic effects of gentamicin on hair cells in the saccule, the putative hearing organ, and utricle of zebrafish. First, adult zebrafish received a single 30 mg/kg intraperitoneal injection of fluorescently-tagged gentamicin (GTTR to determine the distribution of gentamicin within inner ear sensory epithelia. After 4 hours, GTTR was observed in hair cells throughout the saccular and utriclar sensory epithelia. To assess the ototoxic effects of gentamicin, adult zebrafish received a single 250 mg/kg intraperitoneal injection of gentamicin and, 24 hours later, auditory evoked potential recordings (AEPs revealed significant shifts in auditory thresholds compared to untreated controls. Zebrafish were then euthanized, the inner ear fixed, and labeled for apoptotic cells (TUNEL reaction, and the stereociliary bundles of hair cells labeled with fluorescently-tagged phalloidin. Whole mounts of the saccule and utricle were imaged and cells counted. There were significantly more TUNEL-labeled cells found in both organs 4 hours after gentamicin injection compared to vehicle-injected controls. As expected, significantly fewer hair cell bundles were found along the rostral-caudal axis of the saccule and in the extrastriolar and striolar regions of the utricle in gentamicin-treated animals compared to untreated controls. Therefore, as in other species, gentamicin causes significant inner ear sensory hair cell death and auditory dysfunction in zebrafish.

  9. 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.

  10. In Vitro Activity of Polymyxin B in Combination with Various Antibiotics against Extensively Drug-Resistant Enterobacter cloacae with Decreased Susceptibility to Polymyxin B.

    Science.gov (United States)

    Cai, Yiying; Lim, Tze-Peng; Teo, Jocelyn; Sasikala, Suranthran; Lee, Winnie; Hong, Yanjun; Chan, Eric Chun Yong; Tan, Thean Yen; Tan, Thuan-Tong; Koh, Tse Hsien; Hsu, Li Yang; Kwa, Andrea L

    2016-09-01

    Against extensively drug-resistant (XDR) Enterobacter cloacae, combination antibiotic therapy may be the only option. We investigated the activity of various antibiotics in combination with polymyxin B using time-kill studies (TKS). TKS were conducted with four nonclonal XDR E. cloacae isolates with 5 log10 CFU/ml bacteria against maximum, clinically achievable concentrations of polymyxin B alone and in two-drug combinations with 10 different antibiotics. A hollow-fiber infection model (HFIM) simulating clinically relevant polymyxin B and tigecycline dosing regimens was conducted for two isolates over 240 h. Emergence of resistance was quantified using antibiotic-containing (3× MIC) media. Biofitness and stability of resistant phenotypes were determined. All XDR E. cloacae isolates were resistant to all antibiotics except for polymyxin B (polymyxin B MIC, 1 to 4 mg/liter). All isolates harbored metallo-β-lactamases (two with NDM-1, two with IMP-1). In single TKS, all antibiotics alone demonstrated regrowth at 24 h, except amikacin against two strains and polymyxin B and meropenem against one strain each. In combination TKS, only polymyxin B plus tigecycline was bactericidal against all four XDR E. cloacae isolates at 24 h. In HFIM, tigecycline and polymyxin B alone did not exhibit any killing activity. Bactericidal kill was observed at 24 h for both isolates for polymyxin B plus tigecycline; killing was sustained for one isolate but regrowth was observed for the second. Phenotypically stable resistant mutants with reduced in vitro growth rates were observed. Polymyxin B plus tigecycline is a promising combination against XDR E. cloacae However, prolonged and indiscriminate use can result in resistance emergence.

  11. 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...... wrong. Shared decision making might be a solution, as it enables clinician and patient to participate jointly in making a health decision, having discussed the options together with the evidence for their harms as well as benefits. Furthermore, GPs' diagnostic uncertainty - often leading...... 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....

  12. Antibiotic Resistance

    DEFF Research Database (Denmark)

    Munck, Christian

    morbidity and mortality as well as an increase in the cost of treatment. Understanding how bacteria respond to antibiotic exposure gives the foundations for a rational approach to counteract antimicrobial resistance. In the work presented in this thesis, I explore the two fundamental sources...... of antimicrobial resistance: (1) adaptive mutations and (2) horizontal acquisition of resistance genes from antibiotic gene reservoirs. By studying the geno- and phenotypic changes of E. coli in response to single and drug-pair exposures, I uncover the evolutionary trajectories leading to adaptive resistance. I...... to rationally design drug combinations that limit the evolution of antibiotic resistance due to counteracting evolutionary trajectories. My results highlight that an in-depth knowledge about the genetic responses to the individual antimicrobial compounds enables the prediction of responses to drug combinations...

  13. Aerosolized Antibiotics.

    Science.gov (United States)

    Restrepo, Marcos I; Keyt, Holly; Reyes, Luis F

    2015-06-01

    Administration of medications via aerosolization is potentially an ideal strategy to treat airway diseases. This delivery method ensures high concentrations of the medication in the targeted tissues, the airways, with generally lower systemic absorption and systemic adverse effects. Aerosolized antibiotics have been tested as treatment for bacterial infections in patients with cystic fibrosis (CF), non-CF bronchiectasis (NCFB), and ventilator-associated pneumonia (VAP). The most successful application of this to date is treatment of infections in patients with CF. It has been hypothesized that similar success would be seen in NCFB and in difficult-to-treat hospital-acquired infections such as VAP. This review summarizes the available evidence supporting the use of aerosolized antibiotics and addresses the specific considerations that clinicians should recognize when prescribing an aerosolized antibiotic for patients with CF, NCFB, and VAP.

  14. 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.

  15. Increasing antibiotic activity against a multidrug-resistant Acinetobacter spp by essential oils of Citrus limon and Cinnamomum zeylanicum.

    Science.gov (United States)

    Guerra, Felipe Queiroga Sarmento; Mendes, Juliana Moura; Sousa, Janiere Pereira de; Morais-Braga, Maria F B; Santos, Bernadete Helena Cavalcante; Melo Coutinho, Henrique Douglas; Lima, Edeltrudes de Oliveira

    2012-01-01

    The genus Acinetobacter has gained importance in recent years due to involvement in serious infections and antimicrobial resistance. Many plants have been evaluated not only for direct antimicrobial activity, but also as resistance modifying agents. The Essential oil of Citrus limon (EOCL) addition at 156.25 µgmL(-1) (MIC/8) sub-inhibitory concentration in the growth medium led to MIC decrease for amikacin, imipenem and meropenem. The Essential oil of Cinnamomum zeylanicum (EOCZ) addition at 78.125 µg mL(-1) (MIC/8) sub-inhibitory concentrations in the growth medium caused drastic MIC reduction of amikacin. Results of combining antibiotics and essential oils had shown us a synergistic effect with both essential oils/amikacin combinations. An additive effect was observed with the combinations of both essential oils and gentamicin. The results of this study suggest that essential oil of C. limon and C. zeylanicum may suppress the growth of Acinetobacter species and could be a source of metabolites with antibacterial modifying activity.

  16. Fabrication of SERS-active substrates using silver nanofilm-coated porous anodic aluminum oxide for detection of antibiotics.

    Science.gov (United States)

    Chen, Jing; Feng, Shaolong; Gao, Fang; Grant, Edward; Xu, Jie; Wang, Shuo; Huang, Qian; Lu, Xiaonan

    2015-04-01

    We have developed a silver nanofilm-coated porous anodic aluminum oxide (AAO) as a surface-enhanced Raman scattering (SERS)-active substrate for the detection of trace level of chloramphenicol, a representative antibiotic in food systems. The ordered aluminum template generated during the synthesis of AAO serves as a patterned matrix on which a coated silver film replicates the patterned AAO matrix to form a 2-dimensional ordered nanostructure. We used atomic force microscopy and scanning electron microscopy images to determine the morphology of this nanosubstrate, and characterized its localized surface plasmon resonance by ultraviolet-visible reflection. We gauged the SERS effect of this nanosubstrate by confocal micro-Raman spectroscopy (782-nm laser), finding a satisfactory and consistent performance with enhancement factors of approximately 2 × 10(4) and a limit of detection for chloramphenicol of 7.5 ppb. We applied principal component analysis to determine the limit of quantification for chloramphenicol of 10 ppb. Using electromagnetic field theory, we developed a detailed mathematical model to explain the mechanism of Raman signal enhancement of this nanosubstrate. With simple sample pretreatment and separation steps, this silver nanofilm-coated AAO substrate could detect 50 ppb chloramphenicol in milk, indicating good potential as a reliable SERS-active substrate for rapid detection of chemical contaminants in agricultural and food products.

  17. [Quorum sensing systems of regulation, synthesis of phenazine antibiotics, and antifungal (corrected) activity in rhizospheric bacterium Pseudomonas chlororaphis 449].

    Science.gov (United States)

    Veselova, M a; Klein, Sh; Bass, I A; Lipasova, V A; Metlitskaia, A Z; Ovadis, M I; Chernin, L S; Khmel', I A

    2008-12-01

    Strain Pseudomonas chlororaphis 449, an antagonist of a broad spectrum of phytopathogenic microorganisms isolated from the maize rhizosphere, was shown to produce three phenazine antibiotics: phenazine-1-carboxylic acid (PCA), 2-hydroxylphenazine-1-carboxylic acid (2-OH-PCA), and 2-hydroxylphenazine (2-OH-PHZ). Two Quorum Sensing (QS) systems of regulation were identified: PhzIR and CsaI/R. Genes phzI and csaI were cloned and sequenced. Cells of strain 449 synthesize at least three types of AHL: N-butanoyl-L-homoserine lactone (C4-AHL), N-hexanoyl-L-homoserine lactone (C6-AHL), and N-(3-oxo-hexanoyl)-L-homoserine lactone (30C6-AHL). Transposon mutagenesis was used to generate mutants of strain 449 deficient in synthesis of phenazines, which carried inactivated phzA and phzB genes of the phenazine operon and gene phzO. Mutations phzA- and phzB-caused a drastic reduction in the antagonistic activity of bacteria toward phytopathogenic fungi. Both mutants lost the ability to protect cucumber and leguminous plants against phytopathogenic fungi Rhizoctonia solani and Sclerotinia sclerotiorum. These results suggest a significant role of phenazines in the antagonistic activity of P. chlororaphis 449.

  18. Antibiotic Conjugated Fluorescent Carbon Dots as a Theranostic Agent for Controlled Drug Release, Bioimaging, and Enhanced Antimicrobial Activity

    Directory of Open Access Journals (Sweden)

    Mukeshchand Thakur

    2014-01-01

    Full Text Available A novel report on microwave assisted synthesis of bright carbon dots (C-dots using gum arabic (GA and its use as molecular vehicle to ferry ciprofloxacin hydrochloride, a broad spectrum antibiotic, is reported in the present work. Density gradient centrifugation (DGC was used to separate different types of C-dots. After careful analysis of the fractions obtained after centrifugation, ciprofloxacin was attached to synthesize ciprofloxacin conjugated with C-dots (Cipro@C-dots conjugate. Release of ciprofloxacin was found to be extremely regulated under physiological conditions. Cipro@C-dots were found to be biocompatible on Vero cells as compared to free ciprofloxacin (1.2 mM even at very high concentrations. Bare C-dots (∼13 mg mL−1 were used for microbial imaging of the simplest eukaryotic model—Saccharomyces cerevisiae (yeast. Bright green fluorescent was obtained when live imaging was performed to view yeast cells under fluorescent microscope suggesting C-dots incorporation inside the cells. Cipro@C-dots conjugate also showed enhanced antimicrobial activity against both model gram positive and gram negative microorganisms. Thus, the Cipro@C-dots conjugate paves not only a way for bioimaging but also an efficient new nanocarrier for controlled drug release with high antimicrobial activity, thereby serving potential tool for theranostics.

  19. 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.

  20. THE STUDY OF ANTIBIOTIC- AND FAGOSENSITIVITY OF NOSOCOMIAL STRAINS BACTERIA ISOLATED FROM TRANSPLANTED PATIENTS

    Directory of Open Access Journals (Sweden)

    N. I. Gabrielan

    2011-01-01

    Full Text Available Antibiotic and fagosensitivity most etiologically important nosocomial strains of bacteria – Pseudomonas aeru- ginosa, Klebsiella pneumoniae, E. coli, Proteus spp., Staphylococcus spp. were studied. Multiple drug-resistant bacteria as gram-positive and gram-negative, isolated from 8 substrates, had been demonstrated. With regard to the sensitivity of Pseudomonas aeruginosa >40% was observed in 40–50% of the strains to aminoglycosides – aztreonam, amikacin, netilmicin, and only 23–25% of the strains – to gentamicin and levofloxacin (an average of antibiotic susceptibility was 27%. All strains of ESBL Klebsiella drew up and were sensitive only to imipenem, meropenem and aminoglycosides. Specific phages lysed 43–48% of the strains Pseudomonas aeruginosa and Klebsiella pneumoniae, E. coli, Pro- teus spp., multidrug resistant strains of Staphylococcus spp. It is proposed to introduce the use of phages in clinical practice. 

  1. Aminoglycoside ototoxicity in three murine strains and effects on NKCC1 of stria vascularis

    Institute of Scientific and Technical Information of China (English)

    CHU Han-qi; XIONG Hao; Zhou Xiao-qin; HAN Fang; WU Zhen-gong; ZHANG Ping; HUANG Xiao-wen; CUI Yong-hua

    2006-01-01

    Background After establishing a murine model of aminoglycoside antibiotic (AmAn) induced ototoxicity, the sensitivity of AmAn induced ototoxicity in three murine strains and the effect of kanamycin on the expression of Na-K-2C1 cotransporter-1 (NKCC 1) in stria vascularis were investigated.Methods C57BL/6J, CBA/CaJ, NKCC1+/- mice (24 of each strain) were randomly divided into four experimental groups: A: kanamycin alone; B: kanamycin plus 2,3-dihydroxybenzoate; C: 2,3-dihydroxybenzoate alone; and D: control group. Mice were injected with kanamycin or/and 2,3-dihydroxybenzoate twice daily for 14 days. Auditory brainstem response (ABR) was measured and morphology of cochlea delineated with succinate dehydrogenase staining. Expression of NKCC1 in stria vascularis was detected immunohistochemically.Results All three strains in groups A and B developed significant ABR threshold shifts (P<0.01), which were accompanied by outer hair cell loss. NKCC 1 expression in stria vascularis was the weakest in group A (A cf D,P<0.01) and the strongest in groups C and D (P<0.05). CBA/CaJ mice had the highest sensitivity to AmAn.Conclusions Administration of kanamycin established AmAn induced ototoxicity. Kanamycin inhibited the expression of NKCC1 in stria vascularis. 2, 3-dihydroxybenzoate attenuated AmAn induced ototoxicitypossibly by enhancing the expression of NKCC1. Age related hearing loss did not show additional sensitivity to AmAn induced ototoxicity in murine model.

  2. Characterization of a C3 Deoxygenation Pathway Reveals a Key Branch Point in Aminoglycoside Biosynthesis.

    Science.gov (United States)

    Lv, Meinan; Ji, Xinjian; Zhao, Junfeng; Li, Yongzhen; Zhang, Chen; Su, Li; Ding, Wei; Deng, Zixin; Yu, Yi; Zhang, Qi

    2016-05-25

    Apramycin is a clinically interesting aminoglycoside antibiotic (AGA) containing a highly unique bicyclic octose moiety, and this octose is deoxygenated at the C3 position. Although the biosynthetic pathways for most 2-deoxystreptamine-containing AGAs have been well characterized, the pathway for apramycin biosynthesis, including the C3 deoxygenation process, has long remained unknown. Here we report detailed investigation of apramycin biosynthesis by a series of genetic, biochemical and bioinformatical studies. We show that AprD4 is a novel radical S-adenosyl-l-methionine (SAM) enzyme, which uses a noncanonical CX3CX3C motif for binding of a [4Fe-4S] cluster and catalyzes the dehydration of paromamine, a pseudodisaccharide intermediate in apramycin biosynthesis. We also show that AprD3 is an NADPH-dependent reductase that catalyzes the reduction of the dehydrated product from AprD4-catalyzed reaction to generate lividamine, a C3' deoxygenated product of paromamine. AprD4 and AprD3 do not form a tight catalytic complex, as shown by protein complex immunoprecipitation and other assays. The AprD4/AprD3 enzyme system acts on different pseudodisaccharide substrates but does not catalyze the deoxygenation of oxyapramycin, an apramycin analogue containing a C3 hydroxyl group on the octose moiety, suggesting that oxyapramycin and apramycin are partitioned into two parallel pathways at an early biosynthetic stage. Functional dissection of the C6 dehydrogenase AprQ shows the crosstalk between different AGA biosynthetic gene clusters from the apramycin producer Streptomyces tenebrarius, and reveals the remarkable catalytic versatility of AprQ. Our study highlights the intriguing chemistry in apramycin biosynthesis and nature's ingenuity in combinatorial biosynthesis of natural products.

  3. Antiproliferative Activity of Polyether Antibiotic--Cinchona Alkaloid Conjugates Obtained via Click Chemistry.

    Science.gov (United States)

    Skiera, Iwona; Antoszczak, Michał; Trynda, Justyna; Wietrzyk, Joanna; Boratyński, Przemysław; Kacprzak, Karol; Huczyński, Adam

    2015-10-01

    A series of eight new conjugates of salinomycin or monensin and Cinchona alkaloids were obtained by the Cu(I)-catalysed 1,3-dipolar Huisgen cycloaddition (click chemistry) of respective N-propargyl amides of salinomycin or monensin with four different Cinchona alkaloid derived azides. In vitro antiproliferative activity of these conjugates evaluated against three cancer cell lines (LoVo, LoVo/DX, HepG2) showed that four of the compounds exhibited high antiproliferative activity (IC50 below 3.00 μm) and appeared to be less toxic and more selective against normal cells than two standard anticancer drugs.

  4. 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 wi

  5. Whole genome sequencing of diverse Shiga toxin-producing and non-producing Escherichia coli strains reveals a variety of virulence and novel antibiotic resistance plasmids

    Science.gov (United States)

    The genomes of a diverse set of Shiga toxin-producing E. coli strains and the presence of 38 plasmids among all the isolates were determined. Among the novel plasmids found, there were eight that encoded resistance genes to antibiotics, including aminoglycosides, carbapenems, penicillins, cephalosp...

  6. PCR-based site-specific mutagenesis of peptide antibiotics FALL-39 and its biologic activities

    Institute of Scientific and Technical Information of China (English)

    Yun-xia YANG; Yun FENG; Bo-yao WANG; Qi WU

    2004-01-01

    AIM: To construct PGEX-1λT-FALL-39 expression vector and its mutant vector, and study the relationship of function and structure. METHODS: A cDNA encoding mature FALL-39 was cloned from SPCA- 1 cell mRNA and the prokaryotic expression vector PGEX- 1λT-FALL-39 was constructed. Two kinds of polymerase chain reaction (PCR) for the site-direction mutagenesis were used to construct FALL-39 mutant expression vector, FALL-39-Lys-32 and FALL-39-Lys-24. Minimal effective concentration, minimal inhibitory concentration, and minimal bactericidal concentration were used to assay the antibacterial activities of these peptides. Effects of different solution on the antibacterial activity of FALL-39 and FALL-39-Lys-32 were observed by CFU determination. The hemolytic effects of these peptides were also examined on human red blood cells. RESULTS: Two site-specific mutants FALL-39-Lys-32 and FALL-39-Lys24 were obtained by PCR-induced mutagenesis. In comparison with two-step PCR which required two pairs of primers, one step PCR which required one pair of primers is a simple and efficient method for the PCR based site-specific mutagenesis. Using the prokaryotic expression system, the E coli-based products of recombinant FALL39 and its mutant peptides were also obtained. The antibacterial assay showed that FALL-39-Lys-32 and FALL-39-Lys24 were more potential in the antibacterial activity against E coli ML35p and Pseltdomonas aeruginosa ATCC27853 than that of FALL-39, and no increase in hemolysis was observed at the antibacterial concentrations. The antibacterial activity of FALL-39-Lys-32 against E coli was more potent than that of FALL-39 in NaCl-containing LB medium, while its activity was almost the same as FALL-39 in SO2-4 containing Medium E. CONCLUSION: PCR-based mutagensis is a useful model system for studying the structure and function relationship of antimicrobial peptides. Keeping α-helical conformation of FALL-39 and increasing net positive charge can increase the

  7. 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…

  8. 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...

  9. Antimicrobial activity of biopolymer–antibiotic thin films fabricated by advanced pulsed laser methods

    Energy Technology Data Exchange (ETDEWEB)

    Cristescu, R., E-mail: rodica.cristescu@inflpr.ro [National Institute for Lasers, Plasma and Radiation Physics, Lasers Department, P.O. Box MG-36, Bucharest-Magurele (Romania); Popescu, C.; Dorcioman, G.; Miroiu, F.M.; Socol, G.; Mihailescu, I.N. [National Institute for Lasers, Plasma and Radiation Physics, Lasers Department, P.O. Box MG-36, Bucharest-Magurele (Romania); Gittard, S.D.; Miller, P.R.; Narayan, R.J. [Biomedical Engineering, University of North Carolina and North Carolina State University, Chapel Hill, NC 27599-7575 (United States); Enculescu, M. [National Institute for Materials Physics, PO Box MG-7, Bucharest-Magurele (Romania); Chrisey, D.B. [Tulane University, Department of Physics and Engineering Physics, New Orleans, LA (United States)

    2013-08-01

    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.

  10. Enhancement of antibacterial activity of capped silver nanoparticles in combination with antibiotics, on model gram-negative and gram-positive bacteria.

    Science.gov (United States)

    Kora, Aruna Jyothi; Rastogi, Lori

    2013-01-01

    The nanoparticles used in this study were prepared from AgNO3 using NaBH4 in the presence of capping agents such as citrate, sodium dodecyl sulfate, and polyvinylpyrrolidone. The formed nanoparticles were characterized with UV-Vis, TEM, and XRD. The generation of silver nanoparticles was confirmed from the appearance of yellow colour and an absorption maximum between 399 and 404 nm. The produced nanoparticles were found to be spherical in shape and polydisperse. For citrate, SDS, and PVP capped nanoparticles, the average particle sizes were 38.3 ± 13.5, 19.3 ± 6.0, and 16.0 ± 4.8 nm, respectively. The crystallinity of the nanoparticles in FCC structure is confirmed from the SAED and XRD patterns. Also, the combined antibacterial activity of these differently capped nanoparticles with selected antibiotics (streptomycin, ampicillin, and tetracycline) was evaluated on model Gram-negative and Gram-positive bacteria, employing disc diffusion assay. The activity of the tested antibiotics was enhanced in combination with all the stabilized nanoparticles, against both the Gram classes of bacteria. The combined effects of silver nanoparticles and antibiotics were more prominent with PVP capped nanoparticles as compared to citrate and SDS capped ones. The results of this study demonstrate potential therapeutic applications of silver nanoparticles in combination with antibiotics.

  11. Enhancement of Antibacterial Activity of Capped Silver Nanoparticles in Combination with Antibiotics, on Model Gram-Negative and Gram-Positive Bacteria

    Directory of Open Access Journals (Sweden)

    Aruna Jyothi Kora

    2013-01-01

    Full Text Available The nanoparticles used in this study were prepared from AgNO3 using NaBH4 in the presence of capping agents such as citrate, sodium dodecyl sulfate, and polyvinylpyrrolidone. The formed nanoparticles were characterized with UV-Vis, TEM, and XRD. The generation of silver nanoparticles was confirmed from the appearance of yellow colour and an absorption maximum between 399 and 404 nm. The produced nanoparticles were found to be spherical in shape and polydisperse. For citrate, SDS, and PVP capped nanoparticles, the average particle sizes were 38.3±13.5, 19.3±6.0, and 16.0±4.8 nm, respectively. The crystallinity of the nanoparticles in FCC structure is confirmed from the SAED and XRD patterns. Also, the combined antibacterial activity of these differently capped nanoparticles with selected antibiotics (streptomycin, ampicillin, and tetracycline was evaluated on model Gram-negative and Gram-positive bacteria, employing disc diffusion assay. The activity of the tested antibiotics was enhanced in combination with all the stabilized nanoparticles, against both the Gram classes of bacteria. The combined effects of silver nanoparticles and antibiotics were more prominent with PVP capped nanoparticles as compared to citrate and SDS capped ones. The results of this study demonstrate potential therapeutic applications of silver nanoparticles in combination with antibiotics.

  12. First study on antimicriobial activity and synergy between isothiocyanates and antibiotics against selected Gram-negative and Gram-positive pathogenic bacteria from clinical and animal source.

    Science.gov (United States)

    Dias, Carla; Aires, Alfredo; Bennett, Richard N; Rosa, Eduardo A S; Saavedra, Maria J

    2012-05-01

    The emergence of new diseases and the resurgence of several infections that were controlled in the past, associated with recent increase of bacterial resistance have created the necessity for more studies towards to the development of new antimicrobials and new treatment strategies. The aim of the present study was to evaluate the in vitro synergy between different classes of important glucosinolates hydrolysis products-isothiocyanates with antibiotics (gentamycin and vancomycin), against important pathogenic bacteria: Escherichia coli, Enterococcus faecalis, Listeria monocytogenes, Pseudomonas aeruginosa and Staphylococcus aureus. A disc diffusion method was used to evaluate the antibacterial activity. The antimicrobial activity of phytochemicals and combinations between gentamycin, vancomycin and phytochemicals were quantitatively assessed by measuring the inhibitory halos. The results showed a selective antimicrobial effect of isothiocyanates, and this effect was strictly related with their chemical structure. In general the benzylisothiocyanate was the most effective compound against both Gram-positive and Gram-negative bacteria. The Listeria monocytogenes and Staphylococcus aureus were the bacteria most affected either by the phytochemicals alone or by the combination phytochemical-antibiotic. The bacteria Pseudomonas aeruginosa was the less affected pathogen. The most important synergism detected occurred between the commercial antibiotics with benzylisothiocyanate and 2-phenylethylisothiocyanate. In conclusion, some isothiocyanates are effective inhibitors of in vitro bacterial growth, and they can act synergistically with antibiotics.

  13. Antibiotic-Associated Diarrhea

    Science.gov (United States)

    Antibiotic-associated diarrhea Overview By Mayo Clinic Staff Antibiotic-associated diarrhea refers to passing loose, watery stools ... after taking medications used to treat bacterial infections (antibiotics). Most often, antibiotic-associated diarrhea is mild and ...

  14. Tryptophan-containing lipopeptide antibiotics derived from polymyxin B with activity against Gram positive and Gram negative bacteria.

    Science.gov (United States)

    Grau-Campistany, Ariadna; Manresa, Ángeles; Pujol, Montserrat; Rabanal, Francesc; Cajal, Yolanda

    2016-02-01

    Resistance to all known antibiotics is a growing concern worldwide, and has renewed the interest in antimicrobial peptides, a structurally diverse class of amphipathic molecules that essentially act on the bacterial membrane. Propelled by the antimicrobial potential of this compound class, we have designed three new lipopeptides derived from polymyxin B, sp-34, sp-96 and sp-100, with potent antimicrobial activity against both Gram positive and Gram negative bacteria. The three peptides bind with high affinity to lipopolysaccharide as demonstrated by monolayer penetration and dansyl-displacement. The interaction with the cytoplasmic membrane has been elucidated by biophysical experiments with model membranes of POPG or POPE/POPG (6:4), mimicking the Gram positive and Gram negative bacterial membrane. Trp-based fluorescence experiments including steady-state, quenching, anisotropy and FRET, reveal selectivity for anionic phospholipids and deep insertion into the membrane. All three lipopeptides induce membrane fusion and leakage from anionic vesicles, a process that is favored by the presence of POPE. The molecules bind to zwitterionic POPC vesicles, a model of the eukaryotic membrane, but in a different way, with lower affinity, less penetration into the bilayer and no fusion or permeabilization of the membrane. Results in model membranes are consistent with flow cytometry experiments in Escherichia coli and Staphylococcus aureus using a membrane potential sensitive dye (bis-oxonol) and a nucleic acid dye (propidium iodide), suggesting that the mechanism of action is based on membrane binding and collapse of membrane integrity by depolarization and permeabilization.

  15. Optically pure, water-stable metallo-helical ‘flexicate’ assemblies with antibiotic activity

    Science.gov (United States)

    Howson, Suzanne E.; Bolhuis, Albert; Brabec, Viktor; Clarkson, Guy J.; Malina, Jaroslav; Rodger, Alison; Scott, Peter

    2012-01-01

    The helicates—chiral assemblies of two or more metal atoms linked by short or relatively rigid multidentate organic ligands—may be regarded as non-peptide mimetics of α-helices because they are of comparable size and have shown some relevant biological activity. Unfortunately, these beautiful helical compounds have remained difficult to use in the medicinal arena because they contain mixtures of isomers, cannot be optimized for specific purposes, are insoluble, or are too difficult to synthesize. Instead, we have now prepared thermodynamically stable single enantiomers of monometallic units connected by organic linkers. Our highly adaptable self-assembly approach enables the rapid preparation of ranges of water-stable, helicate-like compounds with high stereochemical purity. One such iron(II) ‘flexicate’ system exhibits specific interactions with DNA, promising antimicrobial activity against a Gram-positive bacterium (methicillin-resistant Staphylococcus aureus, MRSA252), but also, unusually, a Gram-negative bacterium (Escherichia coli, MC4100), as well as low toxicity towards a non-mammalian model organism (Caenorhabditis elegans).

  16. RpoS plays a central role in the SOS induction by sub-lethal aminoglycoside concentrations in Vibrio cholerae.

    Directory of Open Access Journals (Sweden)

    Zeynep Baharoglu

    Full Text Available Bacteria encounter sub-inhibitory concentrations of antibiotics in various niches, where these low doses play a key role for antibiotic resistance selection. However, the physiological effects of these sub-lethal concentrations and their observed connection to the cellular mechanisms generating genetic diversification are still poorly understood. It is known that, unlike for the model bacterium Escherichia coli, sub-minimal inhibitory concentrations (sub-MIC of aminoglycosides (AGs induce the SOS response in Vibrio cholerae. SOS is induced upon DNA damage, and since AGs do not directly target DNA, we addressed two issues in this study: how sub-MIC AGs induce SOS in V. cholerae and why they do not do so in E. coli. We found that when bacteria are grown with tobramycin at a concentration 100-fold below the MIC, intracellular reactive oxygen species strongly increase in V. cholerae but not in E. coli. Using flow cytometry and gfp fusions with the SOS regulated promoter of intIA, we followed AG-dependent SOS induction. Testing the different mutation repair pathways, we found that over-expression of the base excision repair (BER pathway protein MutY relieved this SOS induction in V. cholerae, suggesting a role for oxidized guanine in AG-mediated indirect DNA damage. As a corollary, we established that a BER pathway deficient E. coli strain induces SOS in response to sub-MIC AGs. We finally demonstrate that the RpoS general stress regulator prevents oxidative stress-mediated DNA damage formation in E. coli. We further show that AG-mediated SOS induction is conserved among the distantly related Gram negative pathogens Klebsiella pneumoniae and Photorhabdus luminescens, suggesting that E. coli is more of an exception than a paradigm for the physiological response to antibiotics sub-MIC.

  17. 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.

  18. Screening for alternative antibiotics: an investigation into the antimicrobial activities of medicinal food plants of Mauritius.

    Science.gov (United States)

    Mahomoodally, M F; Gurib-Fakim, A; Subratty, A H

    2010-04-01

    The present study was designed to evaluate the antimicrobial activities of 2 endemic medicinal plants; Faujasiopsis flexuosa (Asteraceae) (FF) and Pittosporum senacia (Pittosporaceae) (PS) and 2 exotic medicinal plants, Momordica charantia (Cucurbitaceae) (MC) and Ocimum tenuiflorum (Lamiaceae) (OT) that forms part of local pharmacopoeia of Mauritius and correlate any observed activity with its phytochemical profile. Aqueous and organic fractions of the leaves, fruits, and seeds of these plants were subjected to antimicrobial testing by the disc diffusion method against 8 clinical isolates of bacteria and 2 strains of fungus. It was found that MC, OT, and FF possessed antimicrobial properties against the test organisms. The MIC for MC ranged from 0.5 to 9 mg/mL and that of FF from 2 to 10 mg/mL and the lowest MIC value (0.5 mg/mL) was recorded for the unripe fruits of MC against E. coli. On the other hand, higher concentration of the unripe MC fruit extract of 9 mg/mL was needed to be effective against a resistant strain of Staphylococcus aureus (MRSA). The antimicrobial effect against MRSA was lost upon ripening of the fruits. The methanolic extract of both MC and FF showed highest MIC values compared to the corresponding aqueous extract, which indicates the low efficacy and the need of higher doses of the plant extract. Phytochemical screening of the plants showed the presence of at least tannins, phenols, flavonoids, and alkaloids, which are known antimicrobial phyto-compounds. In conclusion, the observed antimicrobial properties would tend to further validate the medicinal properties of these commonly used endemic medicinal and food plants of Mauritius.

  19. 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, Lívia; Howe, Orla; McCarron, Pauraic; McCann, Malachy; Devereux, Michael

    2016-10-03

    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 centre, with the inclusion of appropriate auxiliary ligands in the structure, offering the opportunity to target different biochemical pathways in bacteria. In this review, we summarize what is currently known about the antibacterial capability of metal-phen complexes and their mechanisms of action.

  20. Efficient removal of antibiotics in a fluidized bed reactor by facile fabricated magnetic powdered activated carbon.

    Science.gov (United States)

    Ma, Jianqing; Yang, Qunfeng; Xu, Dongmei; Zeng, Xiaomei; Wen, Yuezhong; Liu, Weiping

    2017-02-01

    Powdered activated carbons (PACs) with micrometer size are showing great potential for enabling and improving technologies in water treatment. The critical problem in achieving practical application of PAC involves simple, effective fabrication of magnetic PAC and the design of a feasible reactor that can remove pollutants and recover the adsorbent efficiently. Herein, we show that such materials can be fabricated by the combination of PAC and magnetic Fe3O4 with chitosan-Fe hydrogel through a simple co-precipitation method. According to the characterization results, CS-Fe/Fe3O4/PAC with different micrometers in size exhibited excellent magnetic properties. The adsorption of tetracycline was fast and efficient, and 99.9% removal was achieved in 30 min. It also possesses good usability and stability to co-existing ions, organics, and different pH values due to its dispersive interaction nature. Finally, the prepared CS-Fe/Fe3O4/PAC also performed well in the fluidized bed reactor with electromagnetic separation function. It could be easily separated by applying a magnetic field and was effectively in situ regenerated, indicating a potential of practical application for the removal of pollutants from water.

  1. Antibacterial activity of plant extracts and phytochemicals on antibiotic-resistant bacteria Atividade de extratos vegetais e fitofármacos sobre bactérias resistentes a antibióticos

    OpenAIRE

    Nascimento,Gislene G. F.; Juliana Locatelli; Freitas,Paulo C.; Silva,Giuliana L.

    2000-01-01

    The antimicrobial activity of plant extracts and phytochemicals was evaluated with antibiotic susceptible and resistant microorganisms. In addition, the possible synergistic effects when associated with antibiotics were studied. Extracts from the following plants were utilized: Achillea millifolium (yarrow), Caryophyllus aromaticus (clove), Melissa offficinalis (lemon-balm), Ocimun basilucum (basil), Psidium guajava (guava), Punica granatum (pomegranate), Rosmarinus officinalis (rosemary), Sa...

  2. An antibiotic complex from Lysobacter enzymogenes strain C3: antimicrobial activity and role in plant disease control.

    Science.gov (United States)

    Li, S; Jochum, C C; Yu, F; Zaleta-Rivera, K; Du, L; Harris, S D; Yuen, G Y

    2008-06-01

    Lysobacter enzymogenes C3 is a bacterial biological control agent that exhibits antagonism against multiple fungal pathogens. Its antifungal activity was attributed in part to lytic enzymes. In this study, a heat-stable antifungal factor (HSAF), an antibiotic complex consisting of dihydromaltophilin and structurally related macrocyclic lactams, was found to be responsible for antagonism by C3 against fungi and oomycetes in culture. HSAF in purified form exhibited inhibitory activity against a wide range of fungal and oomycetes species in vitro, inhibiting spore germination, and disrupting hyphal polarity in sensitive fungi. When applied to tall fescue leaves as a partially-purified extract, HSAF at 25 mug/ml and higher inhibited germination of conidia of Bipolaris sorokiniana compared with the control. Although application of HSAF at 12.5 mug/ml did not reduce the incidence of conidial germination, it inhibited appressorium formation and suppressed Bipolaris leaf spot development. Two mutant strains of C3 (K19 and DeltaNRPS) that were disrupted in different domains in the hybrid polyketide synthase-nonribosomal peptide synthetase gene for HSAF biosynthesis and had lost the ability to produce HSAF were compared with the wild-type strain for biological control efficacy against Bipolaris leaf spot on tall fescue and Fusarium head blight, caused by Fusarium graminearum, on wheat. Both mutant strains exhibited decreased capacity to reduce the incidence and severity of Bipolaris leaf spot compared with C3. In contrast, the mutant strains were as efficacious as the wild-type strain in reducing the severity of Fusarium head blight. Thus, HSAF appears to be a mechanism for biological control by strain C3 against some, but not all, plant pathogenic fungi.

  3. Analysis of 76 veterinary pharmaceuticals from 13 classes including aminoglycosides in bovine muscle by hydrophilic interaction liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Dasenaki, Marilena E; Michali, Christina S; Thomaidis, Nikolaos S

    2016-06-24

    A multiresidue/multiclass method for the simultaneous determination of 76 veterinary drugs and pharmaceuticals in bovine muscle tissue has been developed and validated according to the requirements of European Commission Decision 2002/657/EC. The analytes belong in 13 different classes, including aminoglycoside antibiotics, whose different physicochemical properties (extremely polar character) render their simultaneous determination with other veterinary drugs quite problematic. The method combines a two-step extraction procedure (extraction with acetonitrile followed by an acidic aqueous buffer extraction) with hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) determination, allowing confirmation and quantification in a single chromatographic run. Further cleanup with solid phase extraction was performed using polymeric SPE cartridges. A thorough ionization study of aminoglycosides was performed in order to increase their sensitivity and significant differences in the abundance of the precursor ions of the analytes were revealed, depending on the composition of the mobile phase tested. Further gradient elution optimization and injection solvent optimization were performed for all target analytes.The method was validated according to the European Commission Decision 2002/657. Quantitative analysis was performed by means of standard addition calibration. Recoveries varied from 37.4% (bromhexine) to 106% (kanamycin) in the lowest validation level and 82% of the compounds showed recovery >70%. Detection capability (CCβ) varied from 2.4 (salinomycin) to 1302 (apramycin) μgkg(-1).

  4. Antimicrobial Activity and Stability of Short and Long Based Arachnid Synthetic Peptides in the Presence of Commercial Antibiotics

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    Ivan Arenas

    2016-02-01

    Full Text Available Four antimicrobial peptides (AMPs named Pin2[G], Pin2[14], P18K and FA1 were chemically synthesized and purified. The four peptides were evaluated in the presence of eight commercial antibiotics against four microorganisms of medical importance: Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The commercial antibiotics used were amoxicillin, azithromycin, ceftriaxone, gentamicin, levofloxacin, sulfamethoxazole, trimethoprim and vancomycin. The best AMP against P. aeruginosa was the peptide FA1, and the best AMP against S. aureus was Pin2[G]. Both FA1 and Pin2[G] were efficient against E. coli, but they were not effective against K. pneumoniae. As K. pneumoniae was resistant to most of the commercial antibiotics, combinations of the AMPs FA1 and Pin2[G] were prepared with these antibiotics. According to the fractional inhibitory concentration (FIC index, the best antimicrobial combinations were obtained with concomitant applications of mixtures of FA1 with levofloxacin and sulfamethoxazole. However, combinations of FA1 or Pin2[G] with other antibiotics showed that total inhibitory effect of the combinations were greater than the sum of the individual effects of either the antimicrobial peptide or the antibiotic. We also evaluated the stability of the AMPs. The AMP Pin2[G] manifested the best performance in saline buffer, in supernatants of bacterial growth and in human blood plasma. Nevertheless, all AMPs were cleaved using endoproteolytic enzymes. These data show advantages and disadvantages of AMPs for potential clinical treatments of bacterial infections, using them in conjunction with commercial antibiotics.

  5. Enhancement of the antibiotic activity of erythromycin by volatile compounds of Lippia alba (Mill. N.E. Brown against Staphylococcus aureus

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    Helenicy N.H. Veras

    2011-01-01

    Full Text Available 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.

  6. Infections in neurologic surgery. The intraventricular use of antibiotics.

    Science.gov (United States)

    Wen, D Y; Bottini, A G; Hall, W A; Haines, S J

    1992-04-01

    Intraventricular antibiotic therapy appears to be a useful treatment modality in those CSF infections in which systemic therapy may fail. Consideration should be given to using this form of treatment when infecting organisms are only sensitive to antibiotics with poor penetration of the CSF (e.g., aminoglycosides and vancomycin) and for cases in which intravenous therapy has failed to sterilize the CSF, toxicity from systemic therapy precludes further increases in dosages, and shunts or other CSF hardware might be expected to reduce the efficacy of systemic therapy by providing a foreign body to harbor organisms. Shunts or reservoirs that are infected may be successfully sterilized with IVT therapy alone or in conjunction with systemic therapy, but this has a lower success rate than cases in which the shunt is removed. There is a wealth of clinical experience with IVT vancomycin and gentamicin that suggests that they are relatively safe. Until more data are available on other aminoglycosides and newer antibiotics, these two agents should be considered the antibiotics of choice for IVT therapy. In situations in which the organism is sensitive to both vancomycin and gentamicin, vancomycin should be used in view of the documented neurotoxicity seen with gentamicin. When gentamicin resistance occurs, amikacin and tobramycin are appropriate alternatives. The high risk of epilepsy with the penicillins and cephalosporins makes them less suited for IVT therapy, although the newer cephalosporins have some promise for IVT therapy. CNS fungal infections can be treated effectively with IVT amphotericin B but with a high risk of significant toxicity. Miconazole appears to be safer than amphotericin B but there is less clinical experience with this drug. Table 1 summarizes the dosages, indications, and toxicity of those antibiotics commonly used for intraventricular administration, which have been reported previously.

  7. Squalamine: an aminosterol antibiotic from the shark.

    OpenAIRE

    1993-01-01

    In recent years, a variety of low molecular weight antibiotics have been isolated from diverse animal species. These agents, which include peptides, lipids, and alkaloids, exhibit antibiotic activity against environmental microbes and are thought to play a role in innate immunity. We report here the discovery of a broad-spectrum steroidal antibiotic isolated from tissues of the dogfish shark Squalus acanthias. This water-soluble antibiotic, which we have named squalamine, exhibits potent bact...

  8. Evaluation of the mutagenic activity of leucinostatins, a novel class of antibiotic peptides produced by Paecilomyces marquandii, in the modul Aspergillus nidulans.

    Science.gov (United States)

    Crebelli, R; Carere, A; Conti, G; Conti, L; Rossi, C; Tuttobello, L

    1988-10-01

    Leucinostatins A, B, C, D, E, G, H, and K were thoroughly investigated for their genotoxic activity using the modul Aspergillus nidulans as the test organism. The results of assays for gene mutation (8-azaguanine resistance and methionine suppressors), gene conversion, mitotic crossing-over and mitotic aneuploidy induction suggest that these peptide antibiotics lack significant mutagenicity and that non-genotoxic mechanism(s) underlie their cytotoxic properties.

  9. Occurrence of Antibiotics and Emerging Contaminants in Dairy Farming

    Science.gov (United States)

    Watanabe, N.; Harter, T.; Bergamaschi, B.

    2007-12-01

    Intense animal husbandry is of growing concern as a potential contamination source of a variety of emerging contaminants including pathogens, naturally occurring and synthetic steroid hormones, and various pharmaceuticals, particularly antibiotics. For example, more than twenty million pounds of antibiotics are sold for use in animal husbandry with 95% going towards therapeutic use. Here, we focus on the application and potential environmental occurrence of pharmaceuticals and disinfectants on dairies. Recommended drug applications are available from national databases. Statistical data on actual usage, however, are not available. We complement national data with interviews and dairy visits for further evaluation of drug and chemical usage (not including pesticides used on crops and fertilizer) and an overall assessment of the potential antibiotics output in dairy waste. We find that aminoglycosides, tetracyclines, and coccidiostats make up much of the total mass of antibiotics used. On dairies using the ionophoric antibiotic monensin as feed additive, monensin makes up a large fraction of the total antibiotics use (by mass). Other chemicals of potential concern include disinfectants used to prevent mastitis, detergents used in the milking parlor, footbath reagents to prevent and treat lameness, and insecticides used to control flies and mites.

  10. Structure of the Antibiotic Resistance Factor Spectinomycin Phosphotransferase from Legionella pneumophila

    Energy Technology Data Exchange (ETDEWEB)

    Fong, D.; Lemke, C; Huang, J; Xiong, B; Berghuis, A

    2010-01-01

    Aminoglycoside phosphotransferases (APHs) constitute a diverse group of enzymes that are often the underlying cause of aminoglycoside resistance in the clinical setting. Several APHs have been extensively characterized, including the elucidation of the three-dimensional structure of two APH(3{prime}) isozymes and an APH(2{double_prime}) enzyme. Although many APHs are plasmid-encoded and are capable of inactivating numerous 2-deoxystreptmaine aminoglycosides with multiple regiospecificity, APH(9)-Ia, isolated from Legionella pneumophila, is an unusual enzyme among the APH family for its chromosomal origin and its specificity for a single non-2-deoxystreptamine aminoglycoside substrate, spectinomycin. We describe here the crystal structures of APH(9)-Ia in its apo form, its binary complex with the nucleotide, AMP, and its ternary complex bound with ADP and spectinomycin. The structures reveal that APH(9)-Ia adopts the bilobal protein kinase-fold, analogous to the APH(3{prime}) and APH(2{double_prime}) enzymes. However, APH(9)-Ia differs significantly from the other two types of APH enzymes in its substrate binding area and that it undergoes a conformation change upon ligand binding. Moreover, kinetic assay experiments indicate that APH(9)-Ia has stringent substrate specificity as it is unable to phosphorylate substrates of choline kinase or methylthioribose kinase despite high structural resemblance. The crystal structures of APH(9)-Ia demonstrate and expand our understanding of the diversity of the APH family, which in turn will facilitate the development of new antibiotics and inhibitors.

  11. DOWN-STREAM SPATIAL DISTRIBUTION OF ANTIBIOTIC RESISTANCE TRAITS ALONG METAL CONTAMINATED STREAM REACHES

    Energy Technology Data Exchange (ETDEWEB)

    Tuckfield, C; J V Mcarthur (NOEMAIL), J

    2007-04-16

    Sediment bacteria samples were collected from three streams in South Carolina, two contaminated with multiple metals (Four Mile Creek and Castor Creek), one uncontaminated (Meyers Branch), and another metal contaminated stream (Lampert Creek) in northern Washington State. Growth plates inoculated with Four Mile Creek sample extracts show bacteria colony growth after incubation on plates containing either one of two aminoglycosides (kanamycin or streptomycin), tetracycline or chloramphenocol. This study analyzes the spatial pattern of antibiotic resistance in culturable sediment bacteria in all four streams that may be due to metal contamination. We summarize the two aminoglycoside resistance measures and the 10 metals concentrations by Principal Components Analysis. Respectively, 63% and 58% of the variability was explained in the 1st principal component of each variable set. We used the respective multivariate summary metrics (i.e. 1st principal component scores) as input measures for exploring the spatial correlation between antibiotic resistance and metal concentration for each stream reach sampled. Results show a significant and negative correlation between metals scores versus aminoglycoside resistance scores and suggest that selection for metal tolerance among sediment bacteria may influence selection for antibiotic resistance differently than previously supposed.. In addition, we borrow a method from geostatistics (variography) wherein a spatial cross-correlation analysis shows that decreasing metal concentrations scores are associated with increasing aminoglycoside resistance scores as the separation distance between sediment samples decreases, but for contaminated streams only. Since these results were counter to our initial expectation and to other experimental evidence for water column bacteria, we suspect our field results are influenced by metal bioavailability in the sediments and by a contaminant promoted interaction or ''cocktail effect

  12. Mitochondrial DNA A1555G mutation screening using a testing kit method and its significance in preventing aminoglycoside-related hearing loss

    Institute of Scientific and Technical Information of China (English)

    LIU Xin; YANG Weiyan; HAN Dongyi; JIN Zhengce; GUAN Minxin; DAI Pu; HUANG Deliang; YUAN Huijun; LI Weiming; YU Fei; ZHANG Xin; KANG Dongyang; CAO Juyang

    2006-01-01

    To report a new screening method for mitochondrial DNA 1555A→G mutation and the results of genotype analysis in 19 maternal inherited deafness pedigrees. Method Five hundred and forty-six non-syndromic neuro-sensory hearing loss patients were tested for 1555A→G mutation using a new compact testing kit, which allows clear distinction between wild type and 1555 A→G mutated mtDNAs. Results Nineteen subjects among the 546 patients (3.48%) were found to carry mtDNA A1555G mutation. The results were confirmed by sequencing in an ABI 3100 Avant sequencer. Conclusions Maternal inherited deafness families are a frequently seen in outpatient group. The detection ofmtDNA 1555 A→G mutation with a low cost, ready to use detection kit is needed and suitable in China for large scale screening and preventive testing before usage of aminoglycoside antibiotics.

  13. Antibiotic susceptibility testing of the Gram-negative bacteria based on flow cytometry

    Directory of Open Access Journals (Sweden)

    Claude Saint-Ruf

    2016-07-01

    Full Text Available Rapidly treating infections with adequate antibiotics is of major importance. This requires a fast and accurate determination of the antibiotic susceptibility of bacterial pathogens. The most frequently used methods are slow because they are based on the measurement of growth inhibition. Faster methods, such as PCR-based detection of determinants of antibiotic resistance, do not always provide relevant information on susceptibility, particularly that which is not genetically based. Consequently, new methods, such as the detection of changes in bacterial physiology caused by antibiotics using flow cytometry and fluorescent viability markers, are being explored. In this study, we assessed whether Alexa Fluor® 633 Hydrazide (AFH, which targets carbonyl groups, can be used for antibiotic susceptibility testing. Carbonylation of cellular macromolecules, which increases in antibiotic-treated cells, is a particularly appropriate to assess for this purpose because it is irreversible. We tested the susceptibility of clinical isolates of Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, to antibiotics from the three classes: β-lactams, aminoglycosides and fluoroquinolones. In addition to AFH, we used TO-PRO®-3, which enters cells with damaged membranes and binds to DNA, and DiBAC4 (3, which enters cells with depolarized membranes. We also monitored antibiotic-induced morphological alterations of bacterial cells by analyzing light scattering signals. Although all tested dyes and light scattering signals allowed for the detection of antibiotic-sensitive cells, AFH proved to be the most suitable for the fast and reliable detection of antibiotic susceptibility.

  14. Antibiotic Susceptibility Testing of the Gram-Negative Bacteria Based on Flow Cytometry.

    Science.gov (United States)

    Saint-Ruf, Claude; Crussard, Steve; Franceschi, Christine; Orenga, Sylvain; Ouattara, Jasmine; Ramjeet, Mahendrasingh; Surre, Jérémy; Matic, Ivan

    2016-01-01

    Rapidly treating infections with adequate antibiotics is of major importance. This requires a fast and accurate determination of the antibiotic susceptibility of bacterial pathogens. The most frequently used methods are slow because they are based on the measurement of growth inhibition. Faster methods, such as PCR-based detection of determinants of antibiotic resistance, do not always provide relevant information on susceptibility, particularly that which is not genetically based. Consequently, new methods, such as the detection of changes in bacterial physiology caused by antibiotics using flow cytometry and fluorescent viability markers, are being explored. In this study, we assessed whether Alexa Fluor® 633 Hydrazide (AFH), which targets carbonyl groups, can be used for antibiotic susceptibility testing. Carbonylation of cellular macromolecules, which increases in antibiotic-treated cells, is a particularly appropriate to assess for this purpose because it is irreversible. We tested the susceptibility of clinical isolates of Gram-negative bacteria, Escherichia coli and Pseudomonas aeruginosa, to antibiotics from the three classes: β-lactams, aminoglycosides, and fluoroquinolones. In addition to AFH, we used TO-PRO®-3, which enters cells with damaged membranes and binds to DNA, and DiBAC4 (3), which enters cells with depolarized membranes. We also monitored antibiotic-induced morphological alterations of bacterial cells by analyzing light scattering signals. Although all tested dyes and light scattering signals allowed for the detection of antibiotic-sensitive cells, AFH proved to be the most suitable for the fast and reliable detection of antibiotic susceptibility.

  15. Antibiotics and breast-feeding: a critical review of the literature.

    Science.gov (United States)

    Chung, Allison M; Reed, Michael D; Blumer, Jeffrey L

    2002-01-01

    Continuous breast-feeding, an integral component of the postpartum period, is often threatened upon maternal initiation of antibiotics. The real risk of antibiotic use while breast-feeding must be carefully analysed with regard to all the variables that influence the extent of antibiotic distribution into breast milk, including breast milk composition, physicochemical properties of the antibiotic (molecular weight, lipid solubility, pH, protein binding), length of feeding, and maternal disposition. In addition, infant disposition, including ability to absorb, metabolize, eliminate, and tolerate any amounts of antibiotic, must also be considered prior to maternal administration of antibiotic. The milk to plasma (M/P) ratio is a frequently quoted parameter used to predict drug distribution into breast milk. However, its utility is questionable and often fraught with misinterpretation. An alternative approach when the amount of antibiotic concentration in breast milk is known (through clinical trials) is to calculate an estimated or expected infant drug exposure factoring in known/expected milk consumption, drug concentration and bioavailability. In this review, the following antibiotic classes and current literature regarding their distribution into breast milk are critically reviewed: beta-lactam antibiotics, fluoroquinolones, sulfonamides, macrolides, aminoglycosides, tetracyclines, nitrofurantoin, metronidazole, vancomycin, clindamycin and chloramphenicol. In the majority of instances, these antibiotics do not distribute into breast milk in sufficient concentrations to be of any clinical consequence in the breast-feeding infant.

  16. Detection of high-level aminoglycoside resistant pattern of Enterococci isolated from urine samples at a tertiary care hospital in Bengaluru

    Directory of Open Access Journals (Sweden)

    Smeeta Huidrom

    2016-01-01

    Full Text Available Aims: Enterococcus species are major nosocomial pathogens and they most commonly cause urinary tract infections (UTIs, exhibiting vancomycin and high-level aminoglycoside resistance (HLAR with increasing frequency, resulting in high mortality of patients with serious enterococcal infections. Detection of resistance is thus of paramount importance. The present study aims to detect and determine the HLAR pattern of Enterococci isolated from urine samples of patients diagnosed with UTI at our hospital. Materials and Methods: This study was carried out at a tertiary care hospital in Bengaluru for a period of 1 year from January 2013 to December 2013. A total of 105 enterococcal strains were isolated from urine samples and speciated as per the scheme of Facklam and Collins. Antibiotic susceptibility was determined for various drugs by Kirby–Bauer disc diffusion method. The results were interpreted as per the Clinical and Laboratory Standards Institute (CLSI guidelines. Results: Ninety-three of the 105 (88.6% isolates showed high-level resistance to gentamicin and/or streptomycin. Combined resistance to both the aminoglycosides, high level gentamicin and streptomycin (HLAR, was seen only in Enterococcus faecalis 20/105 (19.04%. Of the two isolates of Enterococcus faecium, 1 (50% was seen to be resistant to high level gentamicin. The HLAR E. faecalis and E. faecium isolates also showed concordant resistance to multiple antibiotics including vancomycin. Conclusion: This study highlights the need to screen for HLAR in patients suffering from enterococcal infections. Routine screening for HLAR is important to limit the spread of resistance and to have a surveillance program.

  17. Self-enhanced targeted delivery of a cell wall– and membrane-active antibiotics, daptomycin, against staphylococcal pneumonia

    Directory of Open Access Journals (Sweden)

    Hong Jiang

    2016-07-01

    Full Text Available Considering that some antibacterial agents can identify the outer structure of pathogens like cell wall and/or cell membrane, we explored a self-enhanced targeted delivery strategy by which a small amount of the antibiotic molecules were modified on the surface of carriers as targeting ligands of certain bacteria while more antibiotic molecules were loaded inside the carriers, and thus has the potential to improve the drug concentration at the infection site, enhance efficacy and reduce potential toxicity. In this study, a novel targeted delivery system against methicillin-resistant Staphylococcus aureus (MRSA pneumonia was constructed with daptomycin, a lipopeptide antibiotic, which can bind to the cell wall of S. aureus via its hydrophobic tail. Daptomycin was conjugated with N-hydroxysuccinimidyl–polyethylene glycol–1,2-distearoyl-sn-glycero-3-phosphoethanolamine to synthesize a targeting compound (Dapt–PEG–DSPE which could be anchored on the surface of liposomes, while additional daptomycin molecules were encapsulated inside the liposomes. These daptomycin-modified, daptomycin-loaded liposomes (DPD-L[D] showed specific binding to MRSA as detected by flow cytometry and good targeting capabilities in vivo to MRSA-infected lungs in a pneumonia model. DPD-L[D] exhibited more favorable antibacterial efficacy against MRSA than conventional PEGylated liposomal daptomycin both in vitro and in vivo. Our study demonstrates that daptomycin-modified liposomes can enhance MRSA-targeted delivery of encapsulated antibiotic, suggesting a novel drug delivery approach for existing antimicrobial agents.

  18. Assessing the antibiotic susceptibility of freshwater cyanobacteria spp.

    Directory of Open Access Journals (Sweden)

    Elsa eDias

    2015-08-01

    Full Text Available Freshwater is a vehicle for the emergence and dissemination of antibiotic resistance. Cyanobacteria are ubiquitous in freshwater, where they are exposed to antibiotics and resistant organisms, but their role on water resistome was never evaluated. Data concerning the effects of antibiotics on cyanobacteria, obtained by distinct methodologies, is often contradictory. This emphasizes the importance of developing procedures to understand the trends of antibiotic susceptibility in cyanobacteria. In this study we aimed to evaluate the susceptibility of four cyanobacterial isolates from different genera (Microcystis aeruginosa, Aphanizomenon gracile, Chrisosporum bergii, Planktothix agradhii, and among them nine isolates from the same specie (M. aeruginosa to distinct antibiotics (amoxicillin, ceftazidime, ceftriaxone, kanamycine, gentamicine, tetracycline, trimethoprim, nalidixic acid, norfloxacin. We used a method adapted from the bacteria standard broth microdilution. Cyanobacteria were exposed to serial dilution of each antibiotic (0.0015-1.6 mg/L in Z8 medium (20 ± 1 ºC; 14/10 h L/D cycle; light intensity 16 ± 4 µEm-2 s-1. Cell growth was followed overtime (OD450nm/microscopic examination and the minimum inhibitory concentrations (MICs were calculated for each antibiotic/isolate. We found that -lactams exhibited the lower MICs, aminoglycosides, tetracycline and norfloxacine presented intermediate MICs; none of the isolates were susceptible to trimethoprim and nalidixic acid. The reduced susceptibility of all tested cyanobacteria to some antibiotics suggests that they might be naturally non-susceptible to these compounds, or that that they might became non-susceptible due to antibiotic contamination pressure, or to the transfer of genes from resistant bacteria present in the environment.

  19. Vancomycin and High Level Aminoglycoside Resistance in Enterococcus spp. in a Tertiary Health Care Centre: A Therapeutic Concern

    Directory of Open Access Journals (Sweden)

    Seema Mittal

    2016-01-01

    Full Text Available Aims. This study was aimed at knowing the prevalence of vancomycin and high level aminoglycoside resistance in enterococcal strains among clinical samples. Study Design. It was an investigational study. Place and Duration of Study. It was conducted on 100 Enterococcus isolates, in the Department of Microbiology, Pt. BDS PGIMS, Rohtak, over a period of six months from July to December 2014. Methodology. Clinical specimens including urine, pus, blood, semen, vaginal swab, and throat swab were processed and Enterococcus isolates were identified by standard protocols. Antibiotic sensitivity testing of enterococci was performed using Kirby-Bauer disc diffusion method. Results. High level gentamicin resistance (HLGR was more common in urine samples (41.5% followed by blood (36% samples. High level streptomycin resistance (HLSR was more common in pus samples (52.6% followed by blood samples (36%. Resistance to vancomycin was maximum in blood isolates. Conclusion. Enterococci resistant to multiple antimicrobial agents have been recognized. Thus, it is crucial for laboratories to provide accurate antimicrobial resistance patterns for enterococci so that effective therapy and infection control measures can be initiated.

  20. Validation of a Strategy for Cancer Therapy: Delivering Aminoglycoside Drugs to Mitochondria in HeLa Cells.

    Science.gov (United States)

    Abe, Jiro; Yamada, Yuma; Harashima, Hideyoshi

    2016-02-01

    Mitochondria in human cancer cells have been implicated in cancer cell proliferation, invasion, metastasis, and even drug-resistance mechanisms, making them a potential target organelle for the treatment of human malignancies. Gentamicin (GM), an aminoglycoside drug (AG), is a small molecule that functions as an antibiotic and has ototoxic and nephrotoxic characteristics. Thus, the delivery of GM to mitochondria in cancer cells would be an innovative anticancer therapeutic strategy. In this study, we attempted mitochondrial delivery of GM in HeLa cells derived from a human cervical cancer. For the mitochondrial delivery, we used MITO-Porter, a liposomal nanocarrier for mitochondrial delivery via membrane fusion. We first encapsulated GM in the aqueous phase of the carrier to construct GM-MITO-Porter. Flow cytometry analysis and fluorescent microscopy observations permitted us to confirm that the GM-MITO-Porter was efficiently taken up by HeLa cells and accumulated in mitochondria, whereas naked GM was not taken up by the cells. Moreover, cell viability assays using HeLa cells showed that the GM-MITO-Porter induced strong cytotoxic effects related to mitochondrial disorder. This finding is the first report of the mitochondrial delivery of an AG to cancer cells for cancer therapeutic strategy.

  1. Facts about Antibiotic Resistance

    Science.gov (United States)

    ... Cost References Español: Datos breves Facts about Antibiotic Resistance Antibiotic resistance is one of the world’s most pressing public ... antibiotic use is a key strategy to control antibiotic resistance. Antibiotic resistance in children and older adults are ...

  2. Cilia-Associated Genes Play Differing Roles in Aminoglycoside-Induced Hair Cell Death in Zebrafish

    Directory of Open Access Journals (Sweden)

    Tamara M. Stawicki

    2016-07-01

    Full Text Available Hair cells possess a single primary cilium, called the kinocilium, early in development. While the kinocilium is lost in auditory hair cells of most species it is maintained in vestibular hair cells. It has generally been believed that the primary role of the kinocilium and cilia-associated genes in hair cells is in the establishment of the polarity of actin-based stereocilia, the hair cell mechanotransduction apparatus. Through genetic screening and testing of candidate genes in zebrafish (Danio rerio we have found that mutations in multiple cilia genes implicated in intraflagellar transport (dync2h1, wdr35, ift88, and traf3ip, and the ciliary transition zone (cc2d2a, mks1, and cep290 lead to resistance to aminoglycoside-induced hair cell death. These genes appear to have differing roles in hair cells, as mutations in intraflagellar transport genes, but not transition zone genes, lead to defects in kinocilia formation and processes dependent upon hair cell mechanotransduction activity. These mutants highlight a novel role of cilia-associated genes in hair cells, and provide powerful tools for further study.

  3. Cilia-Associated Genes Play Differing Roles in Aminoglycoside-Induced Hair Cell Death in Zebrafish.

    Science.gov (United States)

    Stawicki, Tamara M; Hernandez, Liana; Esterberg, Robert; Linbo, Tor; Owens, Kelly N; Shah, Arish N; Thapa, Nihal; Roberts, Brock; Moens, Cecilia B; Rubel, Edwin W; Raible, David W

    2016-01-01

    Hair cells possess a single primary cilium, called the kinocilium, early in development. While the kinocilium is lost in auditory hair cells of most species it is maintained in vestibular hair cells. It has generally been believed that the primary role of the kinocilium and cilia-associated genes in hair cells is in the establishment of the polarity of actin-based stereocilia, the hair cell mechanotransduction apparatus. Through genetic screening and testing of candidate genes in zebrafish (Danio rerio) we have found that mutations in multiple cilia genes implicated in intraflagellar transport (dync2h1, wdr35, ift88, and traf3ip), and the ciliary transition zone (cc2d2a, mks1, and cep290) lead to resistance to aminoglycoside-induced hair cell death. These genes appear to have differing roles in hair cells, as mutations in intraflagellar transport genes, but not transition zone genes, lead to defects in kinocilia formation and processes dependent upon hair cell mechanotransduction activity. These mutants highlight a novel role of cilia-associated genes in hair cells, and provide powerful tools for further study.

  4. Modeling RNA-ligand interactions: the Rev-binding element RNA-aminoglycoside complex.

    Science.gov (United States)

    Leclerc, F; Cedergren, R

    1998-01-15

    An approach to the modeling of ligand-RNA complexes has been developed by combining three-dimensional structure-activity relationship (3D-SAR) computations with a docking protocol. The ability of 3D-SAR to predict bound conformations of flexible ligands was first assessed by attempting to reconstruct the known, bound conformations of phenyloxazolines complexed with human rhinovirus 14 (HRV14) RNA. Subsequently, the same 3D-SAR analysis was applied to the identification of bound conformations of aminoglycosides which associate with the Rev-binding element (RBE) RNA. Bound conformations were identified by parsing ligand conformational data sets with pharmacophores determined by the 3D-SAR analysis. These "bioactive" structures were docked to the receptor RNA, and optimization of the complex was undertaken by extensive searching of ligand conformational space coupled with molecular dynamics computations. The similarity between the bound conformations of the ligand from the 3D-SAR analysis and those found in the docking protocol suggests that this methodology is valid for the prediction of bound ligand conformations and the modeling of the structure of the ligand-RNA complexes.

  5. The antibiotic activity of some Brazilian medicinal plants Atividade antibiótica de algumas plantas medicinais brasileiras

    Directory of Open Access Journals (Sweden)

    Maria R. Ferreira de Lima

    2006-09-01

    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.As atividades antibióticas de extratos etanólicos de 16 espécies de plantas usadas em medicina popular no Brasil foram determinadas contra Staphylococcus aureus, Micrococcus flavus, Bacillus cereus, B. subtilis, Salmonella enteretidis, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Serratia marcescens, Mycobacterium phlei, M. smegmatis e M. fortuitum, contra as leveduras Candida albicans e C. krusei. Entre os trinta e dois extratos testados, somente aqueles derivados de Lafoensia pacari e Pterodon polygalaeflorus mostraram atividade contra as cepas bacterianas e nenhum deles apresentou atividade contra as leveduras. O

  6. In vitro antibiotic susceptibilities of Yersinia pestis determined by broth microdilution following CLSI methods.

    Science.gov (United States)

    Heine, Henry S; Hershfield, Jeremy; Marchand, Charles; Miller, Lynda; Halasohoris, Stephanie; Purcell, Bret K; Worsham, Patricia L

    2015-04-01

    In vitro susceptibilities to 45 antibiotics were determined for 30 genetically and geographically diverse strains of Yersinia pestis by the broth microdilution method at two temperatures, 28°C and 35°C, following Clinical and Laboratory Standards Institute (CLSI) methods. The Y. pestis strains demonstrated susceptibility to aminoglycosides, quinolones, tetracyclines, β-lactams, cephalosporins, and carbapenems. Only a 1-well shift was observed for the majority of antibiotics between the two temperatures. Establishing and comparing antibiotic susceptibilities of a diverse but specific set of Y. pestis strains by standardized methods and establishing population ranges and MIC50 and MIC90 values provide reference information for assessing new antibiotic agents and also provide a baseline for use in monitoring any future emergence of resistance.

  7. Probiotic lactobacilli and bifidobacteria in a fermented milk product with added fruit preparation reduce antibiotic associated diarrhea and Helicobacter pylori activity.

    Science.gov (United States)

    de Vrese, Michael; Kristen, Holger; Rautenberg, Peter; Laue, Christiane; Schrezenmeir, Jürgen

    2011-11-01

    To investigate matrix-specifity of probiotic effects and particularly of the reduction of antibiotics-associated diarrhea, a controlled, randomized, double-blind study was performed, in which 88 Helicobacter pylori-infected but otherwise healthy subjects were given for eight weeks either a) a probiotic fruit yoghurt "mild" containing Lactobacillus acidophilus LA-5 plus Bifidobacterium lactis BB-12, n = 30), b) the same product but pasteurized after fermentation (n = 29) or c) milk acidified with lactic acid (control, n = 29). During week five, a Helicobacter eradication therapy was performed. Helicobacter activity was measured via 13C-2-urea breath tests and antibiotic-associated diarrhoea and other gastrointestinal complaints were recorded by validated questionnaires. In intervention group a, b and c the mean number of days with diarrhoea was 4, 10 and 10 (Pantibiotics treatment was -1·4 ± 1·1, -1·2 ± 1·1, 2·6 ± 1·1 points/four weeks (Pprobiotic bacteria but (rather) to components of acidified milk (most probably lactic acid). Fruit-yogurt-like fermented milk products with living probiotic bacteria significantly shorten the duration of antibiotics-associated diarrhoea and improve gastrointestinal complaints. Fruit yogurt-like fermented milk is a matrix suitable for probiotic bacteria.

  8. A novel cysteine-free venom peptide with strong antimicrobial activity against antibiotics-resistant pathogens from the scorpion Opistophthalmus glabrifrons.

    Science.gov (United States)

    Bao, Aorigele; Zhong, Jie; Zeng, Xian-Chun; Nie, Yao; Zhang, Lei; Peng, Zhao Feng

    2015-10-01

    Antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus, pose serious threat to human health. The outbreak of antibiotic-resistant pathogens in recent years emphasizes once again the urgent need for the development of new antimicrobial agents. Here, we discovered a novel antimicrobial peptide from the scorpion Opistophthalmus glabrifrons, which was referred to as Opisin. Opisin consists of 19 amino acid residues without disulfide bridges. It is a cationic, amphipathic, and α-helical molecule. Protein sequence homology search revealed that Opisin shares 42.1-5.3% sequence identities to the 17/18-mer antimicrobial peptides from scorpions. Antimicrobial assay showed that Opisin is able to potently inhibit the growth of the tested Gram-positive bacteria with the minimal inhibitory concentration (MIC) values of 4.0-10.0 μM; in contrast, it possesses much lower activity against the tested Gram-negative bacteria and a fungus. It is interesting to see that Opisin is able to strongly inhibit the growth of methicillin- and vancomycin-resistant pathogens with the MICs ranging from 2.0 to 4.0 μM and from 4.0 to 6.0 μM, respectively. We found that at a concentration of 5 × MIC, Opisin completely killed all the cultured methicillin-resistant Staphylococcus aureus. These results suggest that Opisin is a promising therapeutic candidate for the treatment of the antibiotic-resistant bacterial infections.

  9. Catechol siderophores repress the pyochelin pathway and activate the enterobactin pathway in Pseudomonas aeruginosa: an opportunity for siderophore-antibiotic conjugates development.

    Science.gov (United States)

    Gasser, Véronique; Baco, Etienne; Cunrath, Olivier; August, Pamela Saint; Perraud, Quentin; Zill, Nicolas; Schleberger, Christian; Schmidt, Alexander; Paulen, Aurélie; Bumann, Dirk; Mislin, Gaëtan L A; Schalk, Isabelle J

    2016-03-01

    Previous studies have suggested that antibiotic vectorization by siderophores (iron chelators produced by bacteria) considerably increases the efficacy of such drugs. The siderophore serves as a vector: when the pathogen tries to take up iron via the siderophore, it also takes up the antibiotic. Catecholates are among the most common iron-chelating compounds used in synthetic siderophore-antibiotic conjugates. Using reverse transcription polymerase chain reaction and proteomic approaches, we showed that the presence of catecholate compounds in the medium of Pseudomonas aeruginosa led to strong activation of the transcription and expression of the outer membrane transporter PfeA, the ferri-enterobactin importer. Iron-55 uptake assays on bacteria with and without PfeA expression confirmed that catechol compounds imported iron into P. aeruginosa cells via PfeA. Uptake rates were between 0.3 × 10(3) and 2 × 10(3) Fe atoms/bacterium/min according to the used catechol siderophore in iron-restricted medium, and remained as high as 0.8 × 10(3) Fe atoms/bacterium/min for enterobactin, even in iron-rich medium. Reverse transcription polymerase chain reaction and proteomic approaches showed that in parallel to this switching on of PfeA expression, a repression of the expression of pyochelin (PCH) pathway genes (PCH being one of the two siderophores produced by P. aeruginosa for iron acquisition) was observed.

  10. Antibiotic / Antimicrobial Resistance Glossary

    Science.gov (United States)

    ... Submit Search The CDC Get Smart: Know When Antibiotics Work Note: Javascript is disabled or is not ... What Everyone Should Know What You Can Do Antibiotic Resistance Q&As Fast Facts Antibiotics Quiz Glossary ...

  11. Nationwide German Multicenter Study on Prevalence of Antibiotic Resistance in Staphylococcal Bloodstream Isolates and Comparative In Vitro Activities of Quinupristin-Dalfopristin

    Science.gov (United States)

    von Eiff, Christof; Reinert, Ralf René; Kresken, Michael; Brauers, Johannes; Hafner, Dieter; Peters, Georg

    2000-01-01

    Antibiotic-resistant gram-positive bacteria have become an increasing problem in the last two decades. In order to evaluate the prevalence of antibiotic resistance in staphylococcal bloodstream isolates in Germany, 2,042 staphylococci collected in 21 tertiary-care hospitals were investigated during a 3-year period (March 1996 to March 1999). Altogether, 1,448 S. aureus isolates and 594 coagulase-negative staphylococci (CoNS) that comprised 13 different species were included. Furthermore, the antistaphylococcal activities of quinupristin-dalfopristin were compared with those of eight other compounds by the broth microdilution method. The rates of oxacillin resistance in Staphylococcus aureus, S. epidermidis, S. haemolyticus, and other CoNS were 13.5, 69, 90, and 34%, respectively. In oxacillin-resistant strains high rates of resistance (up to 100%) to erythromycin, clindamycin, ciprofloxacin, and gentamicin were also observed. However, no strain appeared to be resistant to vancomycin or quinupristin-dalfopristin. The streptogramin combination exhibited excellent in vitro activity against all staphylococcal species tested, regardless of the patterns of resistance to other drug classes. In terms of MICs at which 90% of the isolates are inhibited, quinupristin-dalfopristin was 2 times more active against S. aureus isolates, 4 to 16 times more active against S. haemolyticus, and 8 to 32 times more active against S. epidermidis than vancomycin or teicoplanin. PMID:10921933

  12. Antibiotics produced by marine bacteria and the evaluation of their activity; Kaiyo saikin no seisansuru kosei busshitsu to sono kassei hyoka

    Energy Technology Data Exchange (ETDEWEB)

    Yoshikawa, K.

    1997-09-10

    Researches continue into physiologically active substances metabolized by marine bacteria and, in this report, some that exhibit antibacterial activity (antibiotics) are introduced. A detailed description is given of a new, peculiar antibiotic named Koromicin discovered in this project. Since a number of terrestrial bacteria have already been investigated, marine halophiles, especially those adhering to large seaweed in eutrophic environments, are taken up in this paper. This is because they are easy to culture. Many are collected in Japan and South-Sea islands, and some are selected for culture in view of their capability for producing active substances. Active compounds are extracted from them, refined, isolated, and their structures are determined. It is found that many of the thus-obtained compounds are those that have already been isolated from marine creatures in the past, but this verifies the effectiveness of selecting the marine bacteria as the source from which to collect physiologically active substances. Koromicin discovered in this process is unique in that it impedes the growth of marine Gram-negative bacteria only. 11 refs., 4 figs., 2 tabs.

  13. Gene Sequence Based Clustering Assists in Dereplication of Pseudoalteromonas luteoviolacea Strains with Identical Inhibitory Activity and Antibiotic Production

    DEFF Research Database (Denmark)

    Vynne, Nikolaj Grønnegaard; Månsson, Maria; Gram, Lone

    2012-01-01

    of the present study was to determine whether such bioactivity differences could be linked to genotypes allowing methods from phylogenetic analysis to aid in selection of strains for biodiscovery. Thirteen P. luteoviolacea strains divided into three chemotypes based on production of known antibiotics and four......Some microbial species are chemically homogenous, and the same secondary metabolites are found in all strains. In contrast, we previously found that five strains of P. luteoviolacea were closely related by 16S rRNA gene sequence but produced two different antibiotic profiles. The purpose...... correlation to chemotypes and inhibition profiles, while clustering based on concatenated 16S rRNA, gyrB, and recA gene sequences resulted in three clusters, two of which uniformly consisted of strains of identical chemotype and inhibition profile. A major time sink in natural products discovery is the effort...

  14. Antibiotic resistance potential of the healthy preterm infant gut microbiome

    Science.gov (United States)

    Shaw, Alexander G.; Sim, Kathleen; Wooldridge, David J.; Li, Ming-Shi; Gharbia, Saheer; Misra, Raju; Kroll, John Simon

    2017-01-01

    Background Few studies have investigated the gut microbiome of infants, fewer still preterm infants. In this study we sought to quantify and interrogate the resistome within a cohort of premature infants using shotgun metagenomic sequencing. We describe the gut microbiomes from preterm but healthy infants, characterising the taxonomic diversity identified and frequency of antibiotic resistance genes detected. Results Dominant clinically important species identified within the microbiomes included C. perfringens, K. pneumoniae and members of the Staphylococci and Enterobacter genera. Screening at the gene level we identified an average of 13 antimicrobial resistance genes per preterm infant, ranging across eight different antibiotic classes, including aminoglycosides and fluoroquinolones. Some antibiotic resistance genes were associated with clinically relevant bacteria, including the identification of mecA and high levels of Staphylococci within some infants. We were able to demonstrate that in a third of the infants the S. aureus identified was unrelated using MLST or metagenome assembly, but low abundance prevented such analysis within the remaining samples. Conclusions We found that the healthy preterm infant gut microbiomes in this study harboured a significant diversity of antibiotic resistance genes. This broad picture of resistances and the wider taxonomic diversity identified raises further caution to the use of antibiotics without consideration of the resident microbial communities. PMID:28149696

  15. Antibiotic resistance potential of the healthy preterm infant gut microbiome

    Directory of Open Access Journals (Sweden)

    Graham Rose

    2017-01-01

    Full Text Available Background Few studies have investigated the gut microbiome of infants, fewer still preterm infants. In this study we sought to quantify and interrogate the resistome within a cohort of premature infants using shotgun metagenomic sequencing. We describe the gut microbiomes from preterm but healthy infants, characterising the taxonomic diversity identified and frequency of antibiotic resistance genes detected. Results Dominant clinically important species identified within the microbiomes included C. perfringens, K. pneumoniae and members of the Staphylococci and Enterobacter genera. Screening at the gene level we identified an average of 13 antimicrobial resistance genes per preterm infant, ranging across eight different antibiotic classes, including aminoglycosides and fluoroquinolones. Some antibiotic resistance genes were associated with clinically relevant bacteria, including the identification of mecA and high levels of Staphylococci within some infants. We were able to demonstrate that in a third of the infants the S. aureus identified was unrelated using MLST or metagenome assembly, but low abundance prevented such analysis within the remaining samples. Conclusions We found that the healthy preterm infant gut microbiomes in this study harboured a significant diversity of antibiotic resistance genes. This broad picture of resistances and the wider taxonomic diversity identified raises further caution to the use of antibiotics without consideration of the resident microbial communities.

  16. Diurnal variations in the occurrence and the fate of hormones and antibiotics in activated sludge wastewater treatment in Oslo, Norway

    Energy Technology Data Exchange (ETDEWEB)

    Plosz, Benedek Gy., E-mail: benedek.plosz@niva.no [Norwegian Institute for Water Research, NIVA, Gaustadalleen 21, NO-0349, Oslo (Norway); Leknes, Henriette [Norwegian Institute for Air Research NILU, 2027 Kjeller (Norway); Liltved, Helge; Thomas, Kevin V. [Norwegian Institute for Water Research, NIVA, Gaustadalleen 21, NO-0349, Oslo (Norway)

    2010-03-15

    We present an assessment of the dynamics in the influent concentration of hormones (estrone, estriol) and antibiotics (trimethoprim, sulfamethoxazole, tetracycline, ciprofloxacin) in the liquid phase including the efficiency of biological municipal wastewater treatment. The concentration of estradiol, 17-{alpha}-ethinylestradiol, doxycycline, oxytetracycline, demeclocycline, chlortetracycline, cefuroxime, cyclophosphamide, and ifosfamide were below the limit of detection in all of the sewage samples collected within this study. Two different types of diurnal variation pattern were identified in the influent mass loads of selected antibiotics and hormones that effectively correlate with daily drug administration patterns and with the expected maximum human hormone release, respectively. The occurrence of natural hormones and antimicrobials, administered every 12 hours, shows a daily trend of decreasing contaminant mass load, having the maximum values in the morning hours. The occurrence of antibiotics, typically administered every 8 hours, indicates a daily peak value in samples collected under the highest hydraulic loading. The efficiency of biological removal of both hormones and antibiotics is shown to be limited. Compared to the values obtained in the influent samples, increased concentrations are observed in the biologically treated effluent for trimethoprim, sulfamethoxazole and ciprofloxacin, mainly as a result of deconjugation processes. Ciprofloxacin is shown as the predominant antimicrobial compound in the effluent, and it is present at quantities approximately 10 fold greater than the total mass of the other of the compounds due to poor removal efficiency and alternating solid-liquid partitioning behaviour. Our results suggest that, to increase the micro-pollutant removal and the chemical dosing efficiency in enhanced tertiary treatment, significant benefits can be derived from the optimisation of reactor design and the development of control schemes that

  17. Investigation on Antibacterial and Antioxidant Activities, Phenolic and Flavonoid Contents of Some Thai Edible Plants as an Alternative for Antibiotics

    OpenAIRE

    Lee, J. H.; S. Cho; Paik, H. D.; Choi, C. W.; Nam, K. T.; Hwang, S. G.; Kim, S.K.

    2014-01-01

    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. ...

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

    Directory of Open Access Journals (Sweden)

    Dragana D Bozic

    2014-01-01

    Interpretation & conclusions: o0 ur 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.

  19. Validation and nephrotoxicity of a simplified once-daily aminoglycoside dosing schedule and guidelines for monitoring therapy.

    Science.gov (United States)

    Prins, J M; Weverling, G J; de Blok, K; van Ketel, R J; Speelman, P

    1996-11-01

    There is no established dosing schedule for once-daily aminoglycoside dosing regimens, and accepted guidelines for monitoring therapy are lacking. We derived a simplified schedule from the Hull and Sarubbi (J. H. Hull and F. A. Sarubbi, Ann. Intern. Med. 85:183-189, 1976) nomogram, for which efficacy and safety in a once-daily dosing regimen were previously demonstrated, and prospectively followed serum aminoglycoside levels in patients. The standard treatment was gentamicin or tobramycin at 4 mg/kg of body weight given intravenously once daily. When the renal function was decreased, the daily dose was reduced, as follows: for an estimated creatinine clearance of between 50 and 80 ml/min, the daily dose was 3.25 mg/kg, for an estimated creatinine clearance of between 30 and 50 ml/min, the daily dose was 2.5 mg/kg, and for an estimated creatinine clearance of below 30 ml/min, the daily dose was 2 mg/kg. A total of 221 patients were studied (184 received gentamicin and 37 received tobramycin). First trough levels above 2 mg/liter were recorded in 11% of the patients, and they all had a baseline creatinine clearance below 50 ml/min, or a substantial decrease in clearance between enrollment and the day that the trough level was obtained. A peak level below 6 mg/liter was recorded in 6% of the patients, and half of them received the lowest daily dose. Twenty-five of the 179 evaluable patients (14%; 95% confidence interval, 9 to 19%) fulfilled the criteria for nephrotoxicity. In a multiple regression analysis, the duration of treatment and the use of other nephrotoxic antibiotics or high-dose furosemide, but not trough levels, were significant risk factors. Since the meaning of low peak levels is unclear and since most studies with multiple daily regimens confirm the lack of an association between trough levels and toxicity, we believe that monitoring of serum drug levels can be restricted to monitoring of trough levels in patients with a creatinine clearance below 50 ml

  20. [Investigation for Filamentous Bacteria Community Diversity in Activated Sludge Under Various Kinds and Concentration Conditions of Antibiotics].

    Science.gov (United States)

    Wang, Run-fang; Wang, Qin; Zhang, Hong; Qi, Rong

    2015-06-01

    Three kinds of synthetic antibiotic (spiramycin, oxytetracycline, streptomycin) wastewater were continuously treated by parallel aerobic biofilm reactors for 6 months, respectively. Sludge bulking phenomenon caused by overgrowth of filamentous bacteria was observed under long-term high rbCOD and high C/N conditions in all reactors as showed by the Eikelboom and Jenkins examinations. The qualitative analysis of filamentous bacterial population in the biofilm and suspended sludge using fluorescence in situ hybridization (FISH) showed that the dominated filamentous bacteria in the bioreactor were N. limicola II and Thiothrix II. Under conditions of different antibiotic concentrations (5 mg x L(-1), 25 mg x L(-1)), there was no obvious change in the COD removal efficiency of the parallel reactors, while the NH4+ -N concentration (about 20 mg x L(-1)) occurred under high streptomycin concentration. The filamentous bacteria abundance was reduced with the increasing antibiotic concentration, especially significant for N. limicola II. Terramycin had a significant inhibitory effect on filamentous bacteria population, followed by Streptomycin and Spiramycin.

  1. Ocorrência e diversidade estrutural de metabólitos fúngicos com atividade antibiótica Occurrence and structural diversity of fungal metabolites with antibiotic activity

    Directory of Open Access Journals (Sweden)

    Jacqueline Aparecida Takahashi

    2008-01-01

    Full Text Available Several reasons motivated the development of new generations of antibiotics, such as their high ability to develop resistance to virtually all kinds of anti-infective agents and the crescent market demand for new drugs to treat special demanding patients. After penicillin discovery, several antibiotics were developed from fungal metabolites, since antibacterial secondary metabolites consists on a fungal endogenous protective mechanism against natural competitors. The aim of this review is to present the structural diversity of antibacterial and antifungal metabolites produced by fungi, mentioning sources of fungal isolates, cultivation process and details on the scope of their antibiotic activity.

  2. Intense association of non-culturable endophytic bacteria with antibiotic-cleansed in vitro watermelon and their activation in degenerating cultures.

    Science.gov (United States)

    Thomas, Pious

    2011-12-01

    The study was undertaken with a view to unravel the source of bacterial colony growth observed in a section of micropropagated triploid watermelon cultures that were supposedly cleansed of the associated endophytic bacteria through antibiotic treatment, and thereafter maintained under stringent sterility checks to prevent lateral intrusion of contaminants. Five different bacteria were retrieved from colony growth-displaying watermelon cultures that were previously treated with gentamycin and five isolates from cefazolin-treated stocks with the organisms showing tolerance to the respective antibiotic. These watermelon cultures were in degeneration phase (over 6 months after the previous sub-culturing), while the actively maintained counterpart stocks appeared healthy with no colony growth on different bacteriological media during tissue-screenings. The latter cultures, however, revealed abundant motile, tetrazolium-stained bacterial cells in microscopy, suggesting tissue colonization by non-culturable endophytes. PCR screening on healthy cultures endorsed tissue colonization by different bacterial phylogenic groups. A few organisms could be activated to cultivation from healthy watermelon stocks through host tissue extract supplementation, which also enhanced the growth of all the organisms. The study indicated that a fraction of antibiotic-tolerant bacteria survived intra-tissue in non-culturable form during the preceding cleansing activity, multiplied to substantial numbers thereafter, and turned cultivable in degenerating cultures contributed by tissue breakdown products. This study brings out the existence of a deep endophyte association in tissue cultures which is not easily dissociable. It also signifies the utility of in vitro system for investigations into plant-endophyte association and to bring normally non-culturable novel organisms to cultivation facilitating their future exploitation.

  3. Toward an Alternative Therapeutic Approach for Skin Infections: Antagonistic Activity of Lactobacilli Against Antibiotic-Resistant Staphylococcus aureus and Pseudomonas aeruginosa.

    Science.gov (United States)

    Hafez, Mohamed M; Maghrabi, Ibrahim A; Zaki, Noha M

    2013-09-01

    The wide spread of antimicrobial resistance has urged the need of alternative therapeutic approach. In this context, probiotic lactobacilli have been reported for the prevention and treatment of many gastrointestinal and urogenital infections. However, very little is known about their antagonistic activity against skin pathogens. Accordingly, the present study aimed to investigate the potential of lactobacilli to interfere with pathogenesis features of two antibiotic-resistant skin pathogens, namely methicillin-resistant Staphylococcus aureus and multiple-resistant Pseudomonas aeruginosa. A total of 49 lactobacilli were recovered, identified and tested for their antagonistic activities against the aforementioned pathogens. Of these, eight isolates were capable of blocking the adherence of pathogens to mammalian cells independent of the skin pathogen tested or model adopted. Moreover, three Lactobacillus isolates (LRA4, LC2 and LR5) effectively prevented the pathogen internalization into epithelial cells in addition to potentiating phagocyte-mediated pathogen killing. Interestingly, the lactobacilli LC2, LF9 and LRA4 markedly inhibited the growth of P. aeruginosa and S. aureus isolates in coculture experiments. Besides, the lactobacilli LRA4, LC2, LR5 and LF9 have counteracted pathogen cytotoxicity. Taken together, the present study revealed some inhibitory activities of lactobacilli against two antibiotic-resistant skin pathogens. Moreover, it revealed two lactobacilli, namely LC2 and LRA4, with antagonistic capacity against different virulence determinants of skin pathogens. These lactobacilli are considered promising probiotic candidates that may represent an alternative therapeutic approach for skin infections.

  4. Influence of linker length and composition on enzymatic activity and ribosomal binding of neomycin dimers.

    Science.gov (United States)

    Watkins, Derrick; Kumar, Sunil; Green, Keith D; Arya, Dev P; Garneau-Tsodikova, Sylvie

    2015-07-01

    The human and bacterial A site rRNA binding as well as the aminoglycoside-modifying enzyme (AME) activity against a series of neomycin B (NEO) dimers is presented. The data indicate that by simple modifications of linker length and composition, substantial differences in rRNA selectivity and AME activity can be obtained. We tested five different AMEs with dimeric NEO dimers that were tethered via triazole, urea, and thiourea linkages. We show that triazole-linked dimers were the worst substrates for most AMEs, with those containing the longer linkers showing the largest decrease in activity. Thiourea-linked dimers that showed a decrease in activity by AMEs also showed increased bacterial A site binding, with one compound (compound 14) even showing substantially reduced human A site binding. The urea-linked dimers showed a substantial decrease in activity by AMEs when a conformationally restrictive phenyl linker was introduced. The information learned herein advances our understanding of the importance of the linker length and composition for the generation of dimeric aminoglycoside antibiotics capable of avoiding the action of AMEs and selective binding to the bacterial rRNA over binding to the human rRNA.

  5. Clonal origin of aminoglycoside-resistant Citrobacter freundii isolates in a Danish county

    DEFF Research Database (Denmark)

    Norskov-Lauritsen, N.; Sandvang, Dorthe; Hedegaard, J.;

    2001-01-01

    During 1997, attention was drawn to an increased frequency of aminoglycoside-resistant Citrobacter freundii in a Danish county, when a total of 24 resistant C. freundii isolates was detected. In this study, 15 such isolates were typed by pulsed-field gel electrophoresis, riboprinting and partial...

  6. A new aspect of aminoglycoside ototoxicity : impairment of cochlear dopamine release

    NARCIS (Netherlands)

    Gáborján, A; Halmos, G; Répássy, G; Vizi, E S

    2001-01-01

    Aminoglycoside ototoxicity is a well-documented process via several pathophysiological pathways. The protective role of cochlear dopamine, released from the lateral olivocochlear efferents, was implicated previously in case of ischemia or acoustic trauma, as it postsynaptically inhibits the effect o

  7. 21 CFR 573.130 - Aminoglycoside 3′-phospho- transferase II.

    Science.gov (United States)

    2010-04-01

    ... genetically modified cotton, oilseed rape, and tomatoes in accordance with the following prescribed conditions... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Aminoglycoside 3â²-phospho- transferase II. 573.130 Section 573.130 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND...

  8. 21 CFR 173.170 - Aminoglycoside 3′-phospho-trans-ferase II.

    Science.gov (United States)

    2010-04-01

    ... development of genetically modified cotton, oilseed rape, and tomatoes in accordance with the following... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Aminoglycoside 3â²-phospho-trans-ferase II. 173.170 Section 173.170 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN...

  9. 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 me

  10. A nanoplex PCR assay for the rapid detection of vancomycin and bifunctional aminoglycoside resistance genes in Enterococcus species

    Directory of Open Access Journals (Sweden)

    Ravichandran Manickam

    2007-12-01

    Full Text Available Abstract Background Enterococci have emerged as a significant cause of nosocomial infections in many parts of the world over the last decade. The most common enterococci strains present in clinical isolates are E. faecalis and E. faecium which have acquired resistant to either gentamicin or vancomycin. The conventional culture test takes 2–5 days to yield complete information of the organism and its antibiotic sensitivity pattern. Hence our present study was focused on developing a nanoplex PCR assay for the rapid detection of vancomycin and bifunctional aminoglycoside resistant enterococci (V-BiA-RE. This assay simultaneously detects 8 genes namely 16S rRNA of Enterococcus genus, ddl of E. faecalis and E. faecium, aacA-aphD that encodes high level gentamicin resistance (HLGR, multilevel vancomycin resistant genotypes such as vanA, vanB, vanC and vanD and one internal control gene. Results Unique and specific primer pairs were designed to amplify the 8 genes. The specificity of the primers was confirmed by DNA sequencing of the nanoplex PCR products and BLAST analysis. The sensitivity and specificity of V-BiA-RE nanoplex PCR assay was evaluated against the conventional culture method. The analytical sensitivity of the assay was found to be 1 ng at the DNA level while the analytical specificity was evaluated with 43 reference enterococci and non-enterococcal strains and was found to be 100%. The diagnostic accuracy was determined using 159 clinical specimens, which showed that 97% of the clinical isolates belonged to E. faecalis, of which 26% showed the HLGR genotype, but none were vancomycin resistant. The presence of an internal control in the V-BiA-RE nanoplex PCR assay helped us to rule out false negative cases. Conclusion The nanoplex PCR assay is robust and can give results within 4 hours about the 8 genes that are essential for the identification of the most common Enterococcus spp. and their antibiotic sensitivity pattern. The PCR assay

  11. Insertion sequence IS256 in canine pyoderma isolates of Staphylococcus pseudintermedius associated with antibiotic resistance.

    Science.gov (United States)

    Casagrande Proietti, P; Bietta, A; Coletti, M; Marenzoni, M L; Scorza, A V; Passamonti, F

    2012-06-15

    Staphylococcus pseudintermedius is the most frequent staphylococcal species isolated from canine pyoderma. The control of S. pseudintermedius infection is often difficult due to the expanded antimicrobial resistance phenotypes. Antibiotic resistance in staphylococcal pathogens is often associated to mobile genetic elements such as the insertion sequence IS256 that was first described as a part of the transposon Tn4001, which confers aminoglycoside resistance in Staphylococcus aureus and in Staphylococcus epidermidis. In this study a collection of 70 S. pseudintermedius isolates from canine pyoderma was used to investigate antimicrobial susceptibility to 15 antibiotics and the presence of IS256, not revealed in S. pseudintermedius yet. Antibiotic resistance profiling demonstrated that all S. pseudintermedius isolates had a multi-drug resistance phenotype, exhibiting simultaneous resistance to at least five antibiotics; indeed methicillin resistant S. pseudintermedius isolates were simultaneously resistant to at least nine antibiotics and all were also gentamicin resistant. PCR analyses revealed the presence of IS256 in 43/70 S. pseudintemedius isolates. The association between the presence of IS256 and the resistance was particularly significant for certain antibiotics: cefovecin, amikacin, gentamicin and oxacillin (χ(2)p-valuepseudintermedius isolates and its association with antibiotic resistance. Our findings suggest that S. pseudintermedius may acquire antibiotic resistance genes through mobile genetic elements which may play a predominant role in the dissemination of multi-drug resistance.

  12. Potential of berberine to enhance antimicrobial activity of commonly used antibiotics for dairy cow mastitis caused by multiple drug-resistant Staphylococcus epidermidis infection.

    Science.gov (United States)

    Zhou, X; Yang, C; Li, Y; Liu, X; Wang, Y

    2015-08-19

    Berberine is a plant alkaloid with antimicrobial activity against a variety of microorganisms. In this study, the antimicrobial properties of berberine against multi-drug resistant field isolates of Staphylococcus epidermidis were investigated using berberine alone or in combination with a commonly used antibiotics in veterinary clinics, including penicillin, lincomycin, and amoxicillin. The results indicated that the minimum inhibitory concentrations of berberine, penicillin, lincomycin, and amoxicillin against field S. epidermidis isolates were 2-512, 0.8-213, 0.4-1024, and 0.4-256 mg/mL, respectively. Furthermore, the synergistic effects of antimicrobial activity against these multi-drug resistant isolates were observed when the berberine was combined with penicillin, lincomycin, or amoxicillin; no antagonistic effect of the combination was detected in any of the clinical isolates. These observations were further confirmed using a time-killing assay, in which a combination of 2 agents yielded a greater than 2.03-2.44 log10 decrease in colony-forming unit/mL compared with each agent alone. These findings suggest that berberine is a promising compound for preventing and treating multi-drug resistant S. epidermidis infected mastitis in dairy cows either alone or in combination with other commonly used antibiotics, such as penicillin, lincomycin, and amoxicillin.

  13. Cytosolic Proteome Profiling of Aminoglycosides Resistant Mycobacterium tuberculosis Clinical Isolates Using MALDI-TOF/MS

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    Sharma, Divakar; Lata, Manju; Singh, Rananjay; Deo, Nirmala; Venkatesan, Krishnamurthy; Bisht, Deepa

    2016-01-01

    Emergence of extensively drug resistant tuberculosis (XDR-TB) is the consequence of the failure of second line TB treatment. Aminoglycosides are the important second line anti-TB drugs used to treat the multi drug resistant tuberculosis (MDR-TB). Main known mechanism of action of aminoglycosides is to inhibit the protein synthesis by inhibiting the normal functioning of ribosome. Primary target of aminoglycosides are the ribosomal RNA and its associated proteins. Various mechanisms have been proposed for aminoglycosides resistance but still some are unsolved. As proteins are involved in most of the biological processes, these act as a potential diagnostic markers and drug targets. In the present study we analyzed the purely cytosolic proteome of amikacin (AK) and kanamycin (KM) resistant Mycobacterium tuberculosis isolates by proteomic and bioinformatic approaches. Twenty protein spots were found to have over expressed in resistant isolates and were identified. Among these Rv3208A, Rv2623, Rv1360, Rv2140c, Rv1636, and Rv2185c are six proteins with unknown functions or undefined role. Docking results showed that AK and KM binds to the conserved domain (DUF, USP-A, Luciferase, PEBP and Polyketidecyclase/dehydrase domain) of these hypothetical proteins and over expression of these proteins might neutralize/modulate the effect of drug molecules. TBPred and GPS-PUP predicted cytoplasmic nature and potential pupylation sites within these identified proteins, respectively. String analysis also suggested that over expressed proteins along with their interactive partners might be involved in aminoglycosides resistance. Cumulative effect of these over expressed proteins could be involved in AK and KM resistance by mitigating the toxicity, repression of drug target and neutralizing affect. These findings need further exploitation for the expansion of newer therapeutics or diagnostic markers against AK and KM resistance so that an extreme condition like XDR-TB can be prevented

  14. The Effect of Calcium Phosphate Particle Shape and Size on their Antibacterial and Osteogenic Activity in the Delivery of Antibiotics in vitro

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    Uskoković, Vuk; Batarni, Samir Shariff; Schweicher, Julien; King, Andrew; Desai, Tejal A.

    2013-01-01

    Powders composed of four morphologically different calcium phosphate particles were prepared by precipitation from aqueous solutions: flaky, brick-like, elongated orthogonal, and spherical. The particles were then loaded with either clindamycin phosphate as the antibiotic of choice, or fluorescein, a model molecule used to assess the drug release properties. A comparison was carried out of the comparative effect of such antibiotic-releasing materials on: sustained drug release profiles; Staphylococcus aureus growth inhibition; and osteogenic propensities in vitro. Raman spectroscopic analysis indicated the presence of various calcium phosphate phases, including monetite (flaky and elongated orthogonal particles), octacalcium phosphate (brick-shaped particles) and hydroxyapatite (spherical particles). Testing the antibiotic-loaded calcium phosphate powders for bacterial growth inhibition demonstrated satisfying antibacterial properties both in broths and on agar plates. All four calcium-phosphate-fluorescein powders exhibited sustained drug release over 21 days. The calcium phosphate sample with the highest specific surface area and the smallest, spherical particle size was the most effective in both drug loading and release, consequently having the highest antibacterial efficiency. Moreover, the highest cell viability, the largest gene expression upregulation of three different osteogenic markers – osteocalcin, osteopontin and Runx2 - as well as the least disrupted cell cytoskeleton and cell morphologies were also noticed for the calcium phosphate powder composed of smallest, spherical nanosized particles. Still, all four powders exerted a viable effect on osteoblastic MC3T3-E1 cells in vitro, as evidenced by both morphological assessments on fluorescently stained cells and measurements of their mitochondrial activity. The obtained results suggest that the nanoscale particle size and the corresponding coarseness of the surface of particle conglomerates as the

  15. Degradation kinetics and mechanism of β-lactam antibiotics by the activation of H2O2 and Na2S2O8 under UV-254nm irradiation.

    Science.gov (United States)

    He, Xuexiang; Mezyk, Stephen P; Michael, Irene; Fatta-Kassinos, Despo; Dionysiou, Dionysios D

    2014-08-30

    The extensive production and usage of antibiotics have led to an increasing occurrence of antibiotic residuals in various aquatic compartments, presenting a significant threat to both ecosystem and human health. This study investigated the degradation of selected β-lactam antibiotics (penicillins: ampicillin, penicillin V, and piperacillin; cephalosporin: cephalothin) by UV-254nm activated H2O2 and S2O8(2-) photochemical processes. The UV irradiation alone resulted in various degrees of direct photolysis of the antibiotics; while the addition of the oxidants improved significantly the removal efficiency. The steady-state radical concentrations were estimated, revealing a non-negligible contribution of hydroxyl radicals in the UV/S2O8(2-) system. Mineralization of the β-lactams could be achieved at high UV fluence, with a slow formation of SO4(2-) and a much lower elimination of total organic carbon (TOC). The transformation mechanisms were also investigated showing the main reaction pathways of hydroxylation (+16Da) at the aromatic ring and/or the sulfur atom, hydrolysis (+18Da) at the β-lactam ring and decarboxylation (-44Da) for the three penicillins. Oxidation of amine group was also observed for ampicillin. This study suggests that UV/H2O2 and UV/S2O8(2-) advanced oxidation processes (AOPs) are capable of degrading β-lactam antibiotics decreasing consequently the antibiotic activity of treated waters.

  16. Antimicrobial Activity and Antibiotic Sensitivity of Three Isolates of Lactic Acid Bacteria From Fermented Fish Product, Budu

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    Liasi, S. A.

    2009-01-01

    Full Text Available Three isolates of lactic acid bacteria (LAB from the fermented food product, Budu, were identified as genus lactobacillus (Lactobacillus casei LA17, Lactobacillus plantarum LA22 and L. paracasei LA02, and the highest population was Lb. paracasei LA02. The antibacterial agent produced by the isolates inhibited the growth of a range of gram-positive and gram-negative microorganisms. Antimicrobial sensitivity test to 18 different types of antibiotic were evaluated using the disc diffusion method. Inhibition zone diameter was measured and calculated from the means of five determinations and expressed in terms of resistance or susceptibility. All the LAB isolates were resistant to colestin sulphate, streptomycin, amikacin, norfloxacin, nalidixic acid, mecillinam, sulphanethoxazole/ trimethoprim, kanamycin, neomycin, bacitracin and gentamycin but susceptible to erythromycin, penicillin G, chloramphenicol, tetracycline, ampicillin and nitrofurantion.

  17. Antibacterial and antibiotic-potentiation activities of the methanol extract of some cameroonian spices against Gram-negative multi-drug resistant phenotypes

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    Voukeng Igor K

    2012-06-01

    Full Text Available Abstract Background The present work was designed to evaluate the antibacterial properties of the methanol extracts of eleven selected Cameroonian spices on multi-drug resistant bacteria (MDR, and their ability to potentiate the effect of some common antibiotics used in therapy. Results The extract of Cinnamomum zeylanicum against Escherichia coli ATCC 8739 and AG100 strains showed the best activities, with the lowest minimal inhibitory concentration (MIC of 64 μg/ml. The extract of Dorstenia psilurus was the most active when tested in the presence of an efflux pump inhibitor, phenylalanine Arginine-β- Naphtylamide (PAβN, a synergistic effect being observed in 56.25 % of the tested bacteria when it was combined with Erythromycin (ERY. Conclusion The present work evidently provides information on the role of some Cameroonian spices in the fight against multi-resistant bacteria.

  18. Pediatric fecal microbiota harbor diverse and novel antibiotic resistance genes.

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    Aimée M Moore

    Full Text Available Emerging antibiotic resistance threatens human health. Gut microbes are an epidemiologically important reservoir of resistance genes (resistome, yet prior studies indicate that the true diversity of gut-associated resistomes has been underestimated. To deeply characterize the pediatric gut-associated resistome, we created metagenomic recombinant libraries in an Escherichia coli host using fecal DNA from 22 healthy infants and children (most without recent antibiotic exposure, and performed functional selections for resistance to 18 antibiotics from eight drug classes. Resistance-conferring DNA fragments were sequenced (Illumina HiSeq 2000, and reads assembled and annotated with the PARFuMS computational pipeline. Resistance to 14 of the 18 antibiotics was found in stools of infants and children. Recovered genes included chloramphenicol acetyltransferases, drug-resistant dihydrofolate reductases, rRNA methyltransferases, transcriptional regulators, multidrug efflux pumps, and every major class of beta-lactamase, aminoglycoside-modifying enzyme, and tetracycline resistance protein. Many resistance-conferring sequences were mobilizable; some had low identity to any known organism, emphasizing cryptic organisms as potentially important resistance reservoirs. We functionally confirmed three novel resistance genes, including a 16S rRNA methylase conferring aminoglycoside resistance, and two tetracycline-resistance proteins nearly identical to a bifidobacterial MFS transporter (B. longum s. longum JDM301. We provide the first report to our knowledge of resistance to folate-synthesis inhibitors conferred by a predicted Nudix hydrolase (part of the folate synthesis pathway. This functional metagenomic survey of gut-associated resistomes, the largest of its kind to date, demonstrates that fecal resistomes of healthy children are far more diverse than previously suspected, that clinically relevant resistance genes are present even without recent selective

  19. Ex vivo treatment with a novel synthetic aminoglycoside NB54 in primary fibroblasts from Rett syndrome patients suppresses MECP2 nonsense mutations.

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    Manuela Vecsler

    Full Text Available BACKGROUND: Nonsense mutations in the X-linked methyl CpG-binding protein 2 (MECP2 comprise a significant proportion of causative MECP2 mutations in Rett syndrome (RTT. Naturally occurring aminoglycosides, such as gentamicin, have been shown to enable partial suppression of nonsense mutations related to several human genetic disorders, however, their clinical applicability has been compromised by parallel findings of severe toxic effects. Recently developed synthetic NB aminoglycosides have demonstrated significantly improved effects compared to gentamicin evident in substantially higher suppression and reduced acute toxicity in vitro. RESULTS: We performed comparative study of suppression effects of the novel NB54 and gentamicin on three MECP2 nonsense mutations (R294X, R270X and R168X common in RTT, using ex vivo treatment of primary fibroblasts from RTT patients harboring these mutations and testing for the C-terminal containing full-length MeCP2. We observed that NB54 induces dose-dependent suppression of MECP2 nonsense mutations more efficiently than gentamicin, which was evident at concentrations as low as 50 µg/ml. NB54 read-through activity was mutation specific, with maximal full-length MeCP2 recovery in R168X (38%, R270X (27% and R294X (18%. In addition, the recovered MeCP2 was translocated to the cell nucleus and moreover led to parallel increase in one of the most important MeCP2 downstream effectors, the brain derived neurotrophic factor (BDNF. CONCLUSION: Our findings suggest that NB54 may induce restoration of the potentially functional MeCP2 in primary RTT fibroblasts and encourage further studies of NB54 and other rationally designed aminoglycoside derivatives as potential therapeutic agents for nonsense MECP2 mutations in RTT.

  20. A rapid drug release system with a NIR light-activated molecular switch for dual-modality photothermal/antibiotic treatments of subcutaneous abscesses.

    Science.gov (United States)

    Chiang, Wei-Lun; Lin, Tzu-Tsen; Sureshbabu, Radhakrishnan; Chia, Wei-Tso; Hsiao, Hsu-Chan; Liu, Hung-Yi; Yang, Chih-Man; Sung, Hsing-Wen

    2015-02-10

    Eradicating subcutaneous bacterial infections remains a significant challenge. This work reports an injectable system of hollow microspheres (HMs) that can rapidly produce localized heat activated by near-infrared (NIR) light and control the release of an antibiotic via a "molecular switch" in their polymer shells, as a combination strategy for treating subcutaneous abscesses. The HMs have a shell of poly(d,l-lactic-co-glycolic acid) (PLGA) and an aqueous core that is comprised of vancomycin (Van) and polypyrrole nanoparticles (PPy NPs), which are photothermal agents. Experimental results demonstrate that the micro-HMs ensure efficiently the spatial stabilization of their encapsulated Van and PPy NPs at the injection site in mice with subcutaneous abscesses. Without NIR irradiation, the HMs elute a negligible drug concentration, but release substantially more when exposed to NIR light, suggesting that this system is suitable as a photothermally-responsive drug delivery system. The combination of photothermally-induced hyperthermia and antibiotic therapy with HMs increases cytotoxicity for bacteria in abscesses, to an extent that is greater than the sum of the two treatments alone, demonstrating a synergistic effect. This treatment platform may find other clinical applications, especially for localized hyperthermia-based cancer therapy.

  1. [Sensitivity of Pseudomonas chlororaphis to antibiotics and chemical tools of plant protection].

    Science.gov (United States)

    Shepelevich, V V; Kiprianova, E A; Iaroshenko, L V; Avdeeva, L V

    2012-01-01

    Examination of sensitivity of 10 Pseudomonas chlororaphis strains belonging to different subspecies to 54 antibiotics has shown that all studied representatives of Pchlororaphis subsp. chlororaphis, P. chlororaphis subsp. aureofaciens and Pchlororaphis subsp. aurantiaca were sensitive to aminoglycoside antibiotics and fluoroquinolones derivatives. Only part of studied strains has shown sensitivity to some beta-lactam antibiotics, imipeneme and meropeneme. In contrast to representatives of two other subspecies both strains of P. chlororaphis subsp. chlororaphis proved to be sensitive to chlortetracycline and cefepime that allows to consider this difference as the characteristic useful for differentiation. All studied P. chlororaphis strains were resistant to chemical fungicides (Scor and Svitch) and the insect growth regulators (Match, Lufox, Engio, Actellik). Resistance of bacteria to these herbicides gives evidence that their combined use is possible.

  2. [Emerging and important antibiotic resistance in Gram negative bacteria: epidemiology, theory and practice].

    Science.gov (United States)

    Nordmann, P; Poirel, L

    2014-04-23

    Emerging and clinically-relevant antibiotic resistance mechanisms among Gram-negative rods are the extended-spectrum beta-lactamases (ESBL), carbapenemases, and 16S RNA methylases conferring resistance to aminoglycosides. Those resistance determinants do confer multiresistance to antibiotics. They are found in Enterobacteriaceae (especially community-acquired isolates, Pseudomonas aeruginosa and Acinetobacter baumannii). Detection of ESBL-producing and carbapenemase-producing isolates rely on the use of rapid diagnostic techniques that have to be performed when a reduced susceptibility to 3rd/4th generation cephalosporins or to carbapenems is observed, respectively. Only an early detection of those emerging resistance traits may contribute to limit their nosocomial spread and to optimize the antibiotic stewardship.

  3. Biology of Acinetobacter baumannii: Pathogenesis, Antibiotic Resistance Mechanisms, and Prospective Treatment Options

    Science.gov (United States)

    Lee, Chang-Ro; Lee, Jung Hun; Park, Moonhee; Park, Kwang Seung; Bae, Il Kwon; Kim, Young Bae; Cha, Chang-Jun; Jeong, Byeong Chul; Lee, Sang Hee

    2017-01-01

    Acinetobacter baumannii is undoubtedly one of the most successful pathogens responsible for hospital-acquired nosocomial infections in the modern healthcare system. Due to the prevalence of infections and outbreaks caused by multi-drug resistant A. baumannii, few antibiotics are effective for treating infections caused by this pathogen. To overcome this problem, knowledge of the pathogenesis and antibiotic resistance mechanisms of A. baumannii is important. In this review, we summarize current studies on the virulence factors that contribute to A. baumannii pathogenesis, including porins, capsular polysaccharides, lipopolysaccharides, phospholipases, outer membrane vesicles, metal acquisition systems, and protein secretion systems. Mechanisms of antibiotic resistance of this organism, including acquirement of β-lactamases, up-regulation of multidrug efflux pumps, modification of aminoglycosides, permeability defects, and alteration of target sites, are also discussed. Lastly, novel prospective treatment options for infections caused by multi-drug resistant A. baumannii are summarized. PMID:28348979

  4. Screening and deciphering antibiotic resistance in Acinetobacter baumannii: a state of the art.

    Science.gov (United States)

    Bonnin, Rémy A; Nordmann, Patrice; Poirel, Laurent

    2013-06-01

    Acinetobacter baumannii, recognized as a serious threat in healthcare facilities, has the ability to develop resistance to antibiotics quite easily. This resistance is related to either gene acquisition (horizontal gene transfer) or mutations in the genome, leading to gene disruption, over- or down-expression of genes. The clinically relevant antibiotic resistances in A. baumannii include resistance to aminoglycosides, broad-spectrum cephalosporins, carbapenems, tigecycline and colistin, which are the last resort antibiotics. The intrinsic and acquired resistance mechanisms of A. baumannii are presented here, with special focus on β-lactam resistance. The most up-to-date techniques for identification, including phenotypical and molecular tests, and screening of those emerging resistance traits are also highlighted. The implementation of early detection and identification of multidrug-resistant A. baumannii is crucial to control their spread.

  5. Accumulation of the antibiotic phenazine-1-carboxylic acid in the rhizosphere of dryland wheat

    Science.gov (United States)

    Natural antibiotics are thought to function in microbial defense, fitness, competitiveness, biocontrol, communication and gene regulation activity, and antibiotic-producing species are commonly found in microbial communities throughout nature. However, the frequency and amount of antibiotic producti...

  6. Kinetics of kill of bacterial conjunctivitis isolates with moxifloxacin, a fluoroquinolone, compared with the aminoglycosides tobramycin and gentamicin

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    Rudolph S Wagner

    2010-01-01

    Full Text Available Rudolph S Wagner1, David B Granet2, Steven J Lichtenstein3, Tiffany Jamison4, Joseph J Dajcs4, Robert D Gross5, Paul Cockrum41New Jersey Medical School, Newark, NJ, USA; 2Ratner Children’s Eye Center, University of California – San Diego, La Jolla, CA, USA; 3University of Illinois College of Medicine at Peoria, Peoria, Illinois, USA; 4Alcon Research, Ltd, Fort Worth, TX, USA; 5Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX, USAPurpose: To compare the kinetics and speed of kill of Streptococcus pneumoniae and Haemophilus influenzae on exposure to three topical ophthalmic antibiotic solutions.Materials and methods: Bacterial conjunctivitis isolates of S. pneumoniae and H. influenzae were exposed to 1:1000 dilutions of moxifloxacin 0.5%, tobramycin 0.3%, gentamicin 0.3%, and water (control. At 15, 30, 60, 120, and 180 minutes after exposure, aliquots were collected, cells were cultured, and viable cell counts were determined using standard microbiological methods.Results: Moxifloxacin achieved 99.9% kill (3-log reduction at approximately 2 hours for S. pneumoniae and at 15 minutes for H. influenzae. Tobramycin and gentamicin did not achieve 3-log reduction of S. pneumoniae during the 180-minute study period. An increase in bacterial growth was noted for these isolates. Gentamicin took more than 120 minutes to achieve the 3-log reduction of H. influenzae and tobramycin did not reach the 3-log reduction of this pathogen during the 180-minute study period.Conclusion: Moxifloxacin killed S. pneumoniae and H. influenzae in vitro faster than tobramycin and gentamicin, suggesting its potential clinical benefit as a first-line treatment for bacterial conjunctivitis to minimize patient symptoms and to limit the contagiousness of the disease.Keywords: kinetics of kill, bacterial conjunctivitis, in vitro, Streptococcus pneumoniae, Haemophilus influenzae, fluoroquinolones, aminoglycosides

  7. Redox biotransformation and delivery of anthracycline anticancer antibiotics: How interpretable structure-activity relationships of lethality using electrophilicity and the London formula for dispersion interaction work.

    Science.gov (United States)

    Pang, Siu-Kwong

    2017-03-30

    Quantum chemical methods and molecular mechanics approaches face a lot of challenges in drug metabolism study because of their either insufficient accuracy or huge computational cost, or lack of clear molecular level pictures for building computational models. Low-cost QSAR methods can often be carried out even though molecular level pictures are not well defined; however, they show difficulty in identifying the mechanisms of drug metabolism and delineating the effects of chemical structures on drug toxicity because a certain amount of molecular descriptors are difficult to be interpreted. In order to make a breakthrough, it was proposed that mechanistically interpretable molecular descriptors were used to correlate with biological activity to establish structure-activity plots. The mechanistically interpretable molecular descriptors used in this study include electrophilicity and the mathematical function in the London formula for dispersion interaction, and they were calculated using quantum chemical methods. The biological activity is the lethality of anthracycline anticancer antibiotics denoted as log LD50, which were obtained by intraperitoneal injection into mice. The results reveal that the plots for electrophilicity, which can be interpreted as redox reactivity of anthracyclines, can describe oxidative degradation for detoxification and reductive bioactivation for toxicity induction. The plots for the dispersion interaction function, which represent the attraction between anthracyclines and biomolecules, can describe efflux from and influx into target cells of toxicity. The plots can also identify three structural scaffolds of anthracyclines that have different metabolic pathways, resulting in their different toxicity behavior. This structure-dependent toxicity behavior revealed in the plots can provide perspectives on design of anthracycline anticancer antibiotics.

  8. Increased structural flexibility at the active site of a fluorophore-conjugated beta-lactamase distinctively impacts its binding toward diverse cephalosporin antibiotics.

    Science.gov (United States)

    Wong, Wai-Ting; Chan, Kwok-Chu; So, Pui-Kin; Yap, Hong-Kin; Chung, Wai-Hong; Leung, Yun-Chung; Wong, Kwok-Yin; Zhao, Yanxiang

    2011-09-09

    The Ω-loop at the active site of β-lactamases exerts significant impact on the kinetics and substrate profile of these enzymes by forming part of the substrate binding site and posing as steric hindrance toward bulky substrates. Mutating certain residues on the Ω-loop has been a general strategy for molecular evolution of β-lactamases to expand their hydrolytic activity toward extended-spectrum antibiotics through a mechanism believed to involve enhanced structural flexibility of the Ω-loop. Yet no structural information is available that demonstrates such flexibility or its relation to substrate profile and enzyme kinetics. Here we report an engineered β-lactamase that contains an environment-sensitive fluorophore conjugated near its active site to probe the structural dynamics of the Ω-loop and to detect the binding of diverse substrates. Our results show that this engineered β-lactamase has improved binding kinetics and positive fluorescence signal toward oxyimino-cephalosporins, but shows little such effect to non-oxyimino-cephalosporins. Structural studies reveal that the Ω-loop adopts a less stabilized structure, and readily undergoes conformational change to accommodate the binding of bulky oxyimino-cephalosporins while no such change is observed for non-oxyimino-cephalosporins. Mutational studies further confirm that this substrate-induced structural change is directly responsible for the positive fluorescence signal specific to oxyimino-cephalosporins. Our data provide mechanistic evidence to support the long-standing model that the evolutionary strategy of mutating the Ω-loop leads to increased structural flexibility of this region, which in turn facilitates the binding of extended spectrum β-lactam antibiotics. The oxyimino-cephalosporin-specific fluorescence profile of our engineered β-lactamase also demonstrates the possibility of designing substrate-selective biosensing systems.

  9. Acute renal failure after high-dose antibiotic bone cement: case report and review of the literature.

    Science.gov (United States)

    James, Alexia; Larson, Trent

    2015-07-01

    High-dose antibiotic-loaded bone cement (ALBC) spacers are commonly used to treat prosthetic joint infections following total hip and knee arthroplasties. This methodology can provide high local antibiotic concentrations while minimizing systemic exposure and toxicity. The occurrence of acute kidney injury (AKI) is rarely reported. Available literature suggests that the rate may be higher than previously thought. We report a case of significant systemic tobramycin absorption with concomitant acute renal failure in a 69-year-old female following the implantation of a high-dose ALBC spacer containing both tobramycin and vancomycin. The tobramycin level 24 h post-surgery was 5.8 mcg/mL. Due to concomitant renal failure, antibiotic clearance was poor and resulted in prolonged exposure to elevated aminoglycoside levels. Recovery of renal function occurred, but clinicians should be vigilant in considering the potential impact ALBC spacers can have on post-operative renal function if antibiotic elution is higher than expected.

  10. 'Break-point Checkerboard Plate' for screening of appropriate antibiotic combinations against multidrug-resistant Pseudomonas aeruginosa.

    Science.gov (United States)

    Tateda, Kazuhiro; Ishii, Yoshikazu; Matsumoto, Tetsuya; Yamaguchi, Keizo

    2006-01-01

    Increase of multiple drug resistant Pseudomonas aeruginosa (MDRP) is becoming a serious problem in the clinical setting. Although the checkerboard method to determine FIC index and synergistic effects of antibiotic combinations is useful, it is not well adapted to a routine test, mainly because of its time-consuming and labor-intensive nature. Here we report 'Break-point Checkerboard Plate', in which breakpoint concentrations, such as 'S' (sensitive) and 'I' (intermediate), were combined in a microtiter plate with 8 antibiotics, including carbapenem, aminoglycoside and fluoroquinolone. The results obtained from 12 strains of MDRP demonstrated a strong synergistic effect of some antibiotic co