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Sample records for nisin resistance mechanism

  1. Spontaneous nisin-resistant Listeria monocytogenes mutants with increased expression of a putative penicillin-binding protein and their sensitivity to various antibiotics

    DEFF Research Database (Denmark)

    Gravesen, Anne; Sorensen, K.; Aarestrup, Frank Møller

    2001-01-01

    A concern regarding the use of bacteriocins, as for example the lantibiotic nisin, for biopreservation of certain food products is the possibility of resistance development and potential cross-resistance to antibiotics in the target organism. The genetic basis for nisin resistance development...... is as yet unknown. We analyzed changes in gene expression following nisin resistance development in Listeria monocytogenes 412 by restriction fragment differential display. The mutant had increased expression of a protein with strong homology to the glycosyltransferase domain of high...... a prevalent nisin resistance mechanism under the employed isolation conditions. Increased expression of the putative PBP may affect the cell wall composition and thereby alter the sensitivity to cell wall-targeting compounds, The mutants had an isolate-specific increase in sensitivity to different beta...

  2. Engineering of Bacillus subtilis 168 for increased nisin resistance

    DEFF Research Database (Denmark)

    Hansen, Mette; Wangari, Romilda; Hansen, Egon Bech

    2009-01-01

    . Bacillus subtilis had been suggested as a potential host for the biosynthesis of nisin but was discarded due to its sensitivity to the lethal action of nisin. In this study, we have reevaluated the potential of B. subtilis as a host organism for the heterologous production of nisin. We applied...

  3. Microbial modeling of thermal resistance of Alicyclobacillus acidoterrestris CRA7152 spores in concentrated orange juice with nisin addition

    Science.gov (United States)

    Peña, Wilmer Edgard Luera; de Massaguer, Pilar Rodriguez; Teixeira, Luciano Quintão

    2009-01-01

    The nisin effect on thermal death of Alicyclobacillus acidoterrestris CRA 7152 spores in concentrated orange juice (64°Brix) was studied. Concentrations of 0, 50, 75 and 100 IU of nisin/ml juice, at temperatures of 92, 95, 98 and 102°C were evaluated. The quadratic polynomial model was used to analyze the effects of the factors and their interaction. Verification of surviving spores was carried out through plating in K medium (pH 3.7). The results showed that the D values without nisin addition were 25.5, 12.9, 6.1 and 2.3 min for 92, 95, 98 and 102°C respectively. With addition of nisin into the juice there was a drop of heat resistance as the concentration was increased at a same temperature. With 30, 50, 75, 100 and 150 IU/ml at 95°C, the D values were 12.34, 11.38, 10.49, 9.49 and 9.42 min respectively, showing that a decrease in the D value up to 27% can be obtained. The second order polynomial model established with r2 = 0.995 showed that the microorganism resistance was affected by the action of temperature followed by the nisin concentration. Nisin therefore is an alternative for reducing the rigor of the A. acidoterrestris CRA 7152 thermal treatment. PMID:24031405

  4. Polyelectrolyte Multicomponent Colloidosomes Loaded with Nisin Z for Enhanced Antimicrobial Activity against Foodborne Resistant Pathogens

    Directory of Open Access Journals (Sweden)

    Taskeen Niaz

    2018-01-01

    Full Text Available Food grade micro- or nano-carrier systems (NCS are being developed to improve the controlled release of antimicrobial agents. To augment the stability of liposomal NCS and to overcome the limitations associated with the use of free bacteriocin (nisin in the food system, multi-component colloidosomes (MCCS were developed by electrostatic interactions between anionic alginate and cationic chitosan (multilayer around phospholipids based liposomes (core. Zeta-sizer results revealed the average diameter of 145 ± 2 nm, 596 ± 3 nm, and 643 ± 5 nm for nano-liposome (NL, chitosomes (chitosan coated NL and MCCS, respectively. Zeta potential values of NCS varied from −4.37 ± 0.16 mV to 33.3 ± 6 mV, thus both chitosomes (CS and MCCS were positively charged. Microstructure analysis by scanning electron microscope (SEM revealed relatively higher size of MCCS with smooth and round morphology. TGA and DSC based experiments revealed that MCCS were thermally more stable than uncoated liposomes. Encapsulation efficiency of nisin in MCCS was observed to be 82.9 ± 4.1%, which was significantly higher than NL (56.5 ± 2.5%. FTIR analyses confirmed the cross-linking between sodium alginate and chitosan layer. Both qualitative (growth kinetics and quantitative (colony forming unit antimicrobial assays revealed that nisin loaded MCCS have superior potential to control resistant foodborne pathogens including Staphylococcus aureus, Listeria monocytogenes, and Enterococcus faecalis, (5.8, 5.4, and 6.1 Log CFUmL−1 reduction, respectively as compared to free nisin, loaded NL or CS. Controlled release kinetics data fitted with Korsmeyer–Peppas model suggested that nisin release from MCCS followed Fickian diffusion. Cytotoxic studies on human blood cells and HepG2 cell lines revealed hemocompatibility and non-toxicity of MCCS. Thus, due to enhanced controlled release, stability and biocompatibility; these multi-component colloidosomes can be useful for

  5. Adhesion force sensing and activation of a membrane-bound sensor to activate nisin efflux pumps in Staphylococcus aureus under mechanical and chemical stresses

    NARCIS (Netherlands)

    Carniello, Vera; Harapanahalli, Akshay K.; Busscher, Henk J.; van der Mei, Henny C.

    2018-01-01

    Nisin-associated-sensitivity-response-regulator (NsaRS) in Staphylococcus aureus is important for its adhesion to surfaces and resistance against antibiotics, like nisin. NsaRS consists of an intra-membrane-located sensor NsaS and a cytoplasmatically-located response-regulator NsaR, which becomes

  6. Mechanism of synergistic inhibition of Listeria monocytogenes growth by lactic acid, monolaurin, and nisin.

    Science.gov (United States)

    Tokarskyy, Oleksandr; Marshall, Douglas L

    2008-12-01

    The combined lactic acid, monolaurin, and nisin effects on time-to-detection (optical density at 600 nm) extension were greater (P Monolaurin exposure caused C12:0 cell membrane incorporation. Lactic acid caused increased monolaurin C12:0 membrane incorporation, while nisin had no influence. We postulate that lactic acid-enhanced monolaurin C12:0 incorporation into the cell membrane increased membrane fluidity resulting in increased nisin activity.

  7. The vancomycin-nisin(1-12) hybrid restores activity against vancomycin resistant enterococci

    NARCIS (Netherlands)

    Arnusch, C.J.; Bonvin, A.M.J.J.; Verel, A.M.; Jansen, W.T.M.; Liskamp, R.M.J.; de Kruijff, B.; Pieters, R.J.; Breukink, E.J.

    2008-01-01

    Lipid II is a crucial component in bacterial cell wall synthesis [Breukink, E., et al. (1999) Science 286, 2361−2364]. It is the target of a number of important antibiotics, which include vancomycin and nisin [Breukink, E., and de Kruijff, B. (2006) Nat. Rev. Drug Discovery 5, 321−332]. Here we show

  8. Comparison between the resistance of benzalkonium chloride-adapted and -nonadapted biofilms of Listeria monocyogenes to modified atmosphere packaging and nisin once transferred to mussels.

    Science.gov (United States)

    Saá Ibusquiza, P; Herrera, J J R; Cabo, M L

    2011-07-01

    Benzalkonium chloride-adapted and -nonadapted Listeria monocytogenes biofilm cells were transferred by contact to cooked or live mussels and packed in rich CO(2) and O(2), respectively. The viabilities of transferred cells during storage of these packed samples at 2.5 °C were compared. In addition, in cooked mussels the combined effect of CO(2) and nisin against the survival of L. monocytogenes was also studied by using a first-order factorial design. The results obtained demonstrated that biofilms formed by benzalkonium chloride-adapted L. monocytogenes cells could be more resistant to the application of modified atmospheres rich in CO(2) and nisin once they have been transferred to cooked mussels by contact (simulating cross-contamination). This implies an increase in the risk associated with the presence of these cells in food processing plants. Significant empirical equations obtained after 7, 11, and 20 days showed an inhibitory effect of CO(2) and nisin against L. monocytogenes. However, a significant positive interaction between both variables highlights an incompatibility between CO(2) and nisin at high concentrations. Results also demonstrated that L. monocytogenes could persist after cross-contamination during the processing of live mussels, so L. monocytogenes is of concern as a contaminant in live mussels packaged in high-O(2) atmospheres. Copyright ©, International Association for Food Protection

  9. Carbon dioxide and nisin act synergistically on Listeria monocytogenes

    DEFF Research Database (Denmark)

    Nilsson, Lilian; Chen, Y.H.; Chikindas, M.L.

    2000-01-01

    This paper examines the synergistic action of carbon dioxide and nisin on Listeria monocytogenes Scott A wild-type and nisin-resistant (Nis(r)) cells grown in broth at 4 degrees C. Carbon dioxide extended the lag phase and decreased the specific growth rate of both strains, but to a greater degree...

  10. A luminescent nisin biosensor

    Science.gov (United States)

    Immonen, Nina; Karp, Matti

    2006-02-01

    Nisin is a lantibiotic, an antibacterial peptide produced by certain Lactococcus lactis strains that kills or inhibits the growth of other bacteria. Nisin is widely used as a food preservative, and its long-time use suggests that it can be generally regarded as safe. We have developed a method for determining the amount of nisin in food samples that is based on luminescent biosensor bacteria. Bacterial luciferase operon luxABCDE was inserted into plasmid pNZ8048, and the construct was transformed by electroporation into Lc. lactis strain NZ9800, whose ability to produce nisin has been erased by deletion of the gene nisA. The operon luxABCDE has been modified to be functional in gram-positive bacteria to confer a bioluminescent phenotype without the requirement of adding an exogenous substrate. In the plasmid pNZ8048, the operon was placed under control of the nisin-inducible nisA promoter. The chromosomal nisRK genes of Lc. lactis NZ9800 allow it to sense nisin in the environment and relay this signal via signal transduction proteins NisK and NisR to initiate transcription from nisA promoter. In the case of our sensor bacteria, this leads to production of luciferase and, thus, luminescence that can be directly measured from living bacteria. Luminescence can be detected as early as within minutes of induction. The nisin assay described here provides a detection limit in the sub-picogram level per ml, and a linear area between 1 - 1000 pg/ml. The sensitivity of this assay exceeds the performance of all previously published methods.

  11. Isolation of Lactococcus lactis Mutants Simultaneously Resistant to the Cell Wall-Active Bacteriocin Lcn972, Lysozyme, Nisin, and Bacteriophage c2

    Science.gov (United States)

    Roces, Clara; Courtin, Pascal; Kulakauskas, Saulius; Rodríguez, Ana; Chapot-Chartier, Marie-Pierre

    2012-01-01

    Lactococcin 972 (Lcn972) is a nonlantibiotic bacteriocin that inhibits cell wall biosynthesis by binding to lipid II. In this work, two mutants resistant to Lcn972, Lactococcus lactis D1 and D1-20, with high (>320 arbitrary units [AU]/ml) and low (80 AU/ml) susceptibilities, respectively, have been isolated. Resistance to Lcn972 did not impose a burden to growth under laboratory conditions, nor did it substantially alter the physicochemical properties of the cell surface. However, the peptidoglycan of the mutants featured a higher content of muropeptides with tripeptide side chains than the wild-type strain, linking for the first time peptidoglycan remodelling to bacteriocin resistance. Moreover, L. lactis lacking a functional d,d-carboxypeptidase DacA (i.e., with a high content of pentapeptide side chain muropeptides) was shown to be more susceptible to Lcn972. Cross-resistance to lysozyme and nisin and enhanced susceptibility to penicillin G and bacitracin was also observed. Intriguingly, the Lcn972-resistant mutants were not infected by the lytic phage c2 and less efficiently infected by phage sk1. Lack of c2 infectivity was linked to a 22.6-kbp chromosomal deletion encompassing the phage receptor protein gene pip. The deletion also included maltose metabolic genes and the two-component system (TCS) F. However, a clear correlation between these genes and resistance to Lcn972 could not be clearly established, pointing to the presence of as-yet-unidentified mutations that account for Lcn972 resistance. PMID:22504807

  12. Release Kinetics of Nisin from Chitosan-Alginate Complex Films.

    Science.gov (United States)

    Chandrasekar, Vaishnavi; Coupland, John N; Anantheswaran, Ramaswamy C

    2016-10-01

    Understanding the release kinetics of antimicrobials from polymer films is important in the design of effective antimicrobial packaging films. The release kinetics of nisin (30 mg/film) from chitosan-alginate polyelectric complex films prepared using various fractions of alginate (33%, 50%, and 66%) was investigated into an aqueous release medium. Films containing higher alginate fractions showed significantly lower (P < 0.05) degree of swelling in water. Total amount of nisin released from films into an aqueous system decreased significantly (P < 0.05) with an increase in alginate concentration. The mechanism of diffusion of nisin from all films was found to be Fickian, and diffusion coefficients varied from 0.872 × 10 -9 to 8.034 ×10 -9 cm 2 /s. Strong complexation was confirmed between chitosan and alginate polymers within the films using isothermal titration calorimetry and viscosity studies, which affects swelling of films and subsequent nisin release. Complexation was also confirmed between nisin and alginate, which limited the amount of free nisin available for diffusion from films. These low-swelling biopolymer complexes have potential to be used as antimicrobial packaging films with sustained nisin release characteristics. © 2016 Institute of Food Technologists®.

  13. 21 CFR 184.1538 - Nisin preparation.

    Science.gov (United States)

    2010-04-01

    ... Specific Substances Affirmed as GRAS § 184.1538 Nisin preparation. (a) Nisin preparation is derived from pure culture fermentations of certain strains of Streptococcus lactis Lancefield Group N. Nisin preparation contains nisin (CAS Reg. No. 1414-45-5), a group of related peptides with antibiotic activity. (b...

  14. A Bioengineered Nisin Derivative, M21A, in Combination with Food Grade Additives Eradicates Biofilms of Listeria monocytogenes

    Science.gov (United States)

    Smith, Muireann K.; Draper, Lorraine A.; Hazelhoff, Pieter-Jan; Cotter, Paul D.; Ross, R. P.; Hill, Colin

    2016-01-01

    The burden of foodborne disease has large economic and social consequences worldwide. Despite strict regulations, a number of pathogens persist within the food environment, which is greatly contributed to by a build-up of resistance mechanisms and also through the formation of biofilms. Biofilms have been shown to be highly resistant to a number of antimicrobials and can be extremely difficult to remove once they are established. In parallel, the growing concern of consumers regarding the use of chemically derived antimicrobials within food has led to a drive toward more natural products. As a consequence, the use of naturally derived antimicrobials has become of particular interest. In this study we investigated the efficacy of nisin A and its bioengineered derivative M21A in combination with food grade additives to treat biofilms of a representative foodborne disease isolate of Listeria monocytogenes. Investigations revealed the enhanced antimicrobial effects, in liquid culture, of M21A in combination with citric acid or cinnamaldehyde over its wild type nisin A counterpart. Subsequently, an investigation was conducted into the effects of these combinations on an established biofilm of the same strain. Nisin M21A (0.1 μg/ml) alone or in combination with cinnamaldehyde (35 μg/ml) or citric acid (175 μg/ml) performed significantly better than combinations involving nisin A. All combinations of M21A with either citric acid or cinnamaldehyde eradicated the L. monocytogenes biofilm (in relation to a non-biofilm control). We conclude that M21A in combination with available food additives could further enhance the antimicrobial treatment of biofilms within the food industry, simply by substituting nisin A with M21A in current commercial products such as Nisaplin® (Danisco, DuPont). PMID:27965658

  15. A bioengineered nisin derivative, M21A, in combination with food grade additives eradicates biofilms of Listeria monocytogenes.

    Directory of Open Access Journals (Sweden)

    Lorraine Anne Draper

    2016-11-01

    Full Text Available The burden of foodborne disease has large economic and social consequences worldwide. Despite strict regulations, a number of pathogens persist within the food environment, which is greatly contributed to by a build-up of resistance mechanisms and also through the formation of biofilms. Biofilms have been shown to be highly resistant to a number of antimicrobials and can be extremely difficult to remove once they are established. In parallel, the growing concern of consumers regarding the use of chemically derived antimicrobials within food has led to a drive towards more natural products. As a consequence, the use of naturally derived antimicrobials has become of particular interest. In this study we investigated the efficacy of nisin A and its bioengineered derivative M21A in combination with food grade additives to treat biofilms of a representative strain of Listeria monocytogenes. Investigations revealed the enhanced antimicrobial effects, in liquid culture, of M21A in combination with citric acid or cinnamaldehyde over its wild type nisin A counterpart. Subsequently, an investigation was conducted into the effects of these combinations on an established biofilm of the same strain. Nisin M21A (0.1 µg/ml alone or in combination with cinnamaldehyde (35 µg/ml or citric acid (175 µg/ml performed significantly better than combinations involving nisin A. All combinations of M21A with either citric acid or cinnamaldehyde eradicated the L. monocytogenes biofilm (in relation to a non-biofilm control. We conclude that M21A in combination with available food additives could further enhance the antimicrobial treatment of biofilms within the food industry, simply by substituting nisin A with M21A in current commercial products such as Nisaplin (Danisco, DuPont.

  16. Development and Characterization of Nisin Nanoparticles as Potential Alternative for the Recurrent Vaginal Candidiasis Treatment.

    Science.gov (United States)

    de Abreu, Letícia Coli Louvisse; Todaro, Valerio; Sathler, Plinio Cunha; da Silva, Luiz Cláudio Rodrigues Pereira; do Carmo, Flávia Almada; Costa, Cleonice Marques; Toma, Helena Keiko; Castro, Helena Carla; Rodrigues, Carlos Rangel; de Sousa, Valeria Pereira; Cabral, Lucio Mendes

    2016-12-01

    The aim of this work was the development and characterization of nisin-loaded nanoparticles and the evaluation of its potential antifungal activity. Candidiasis is a fungal infection caused by Candida sp. considered as one of the major public health problem currently. The discovery of antifungal agents that present a reduced or null resistance of Candida sp. and the development of more efficient drug release mechanisms are necessary for the improvement of candidiasis treatment. Nisin, a bacteriocin commercially available for more than 50 years, exhibits antibacterial action in food products with potential antifungal activity. Among several alternatives used to modulate antifungal activity of bacteriocins, polymeric nanoparticles have received great attention due to an effective drug release control and reduction of therapeutic dose, besides the minimization of adverse effects by the preferential accumulation in specific tissues. The nisin nanoparticles were prepared by double emulsification and solvent evaporation methods. Nanoparticles were characterized by dynamic light scattering, zeta potential, Fourier transform infrared, X-ray diffraction, differential scanning calorimetry, and scanning electron microscopy. Antifungal activity was accessed by pour plate method and cell counting using Candida albicans strains. The in vitro release profile and in vitro permeation studies were performed using dialysis bag method and pig vaginal mucosa in Franz diffusion cell, respectively. The results revealed nisin nanoparticles (300 nm) with spherical shape and high loading efficiency (93.88 ± 3.26%). In vitro test results suggest a promising application of these nanosystems as a prophylactic agent in recurrent vulvovaginal candidiasis and other gynecological diseases.

  17. Mechanisms of Antibiotic Resistance

    Science.gov (United States)

    Munita, Jose M.; Arias, Cesar A.

    2015-01-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting that reservoirs of antibiotic-resistant bacteria are present outside the hospital. The bacterial response to the antibiotic “attack” is the prime example of bacterial adaptation and the pinnacle of evolution. “Survival of the fittest” is a consequence of an immense genetic plasticity of bacterial pathogens that trigger specific responses that result in mutational adaptations, acquisition of genetic material or alteration of gene expression producing resistance to virtually all antibiotics currently available in clinical practice. Therefore, understanding the biochemical and genetic basis of resistance is of paramount importance to design strategies to curtail the emergence and spread of resistance and devise innovative therapeutic approaches against multidrug-resistant organisms. In this chapter, we will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice providing specific examples in relevant bacterial pathogens. PMID:27227291

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

    Science.gov (United States)

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

    2013-12-01

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

  19. Mechanisms of ouabain resistance

    International Nuclear Information System (INIS)

    Schulz, J.T. III.

    1987-01-01

    Experiments were designed to investigate the mechanism of ouabain resistance in two distinct types of transfected cells derived from ouabain-sensitive CV-1 cell parents. The first type of transfectant is the recipient of a gene encoding the alpha subunit of the rodent renal Na,K-ATPase (R-alphal gene); the second type of transfectant is the recipient of the mouse ouabain resistance gene. Measurements of 86 Rb + uptake and Na,K=ATPase activity in R-alphal gene transfectant cells and CV-1 parent cells indicate that the ouabain-resistant phenotype of the transfectants is due to expression of a relatively ouabain-insensitive Na,K=ATPase. CV-1 parent cells express one component of ouabain sensitive 86 Rb + uptake and one component of ouabain-sensitive Na, K-ATPase activity. R-alpha 1 gene transfectants express the parental forms of ouabain-sensitive 86 Rb + uptake and Na,K-ATPase activity, but in addition express new,relatively ouabain-insensitive forms of 86 Rb + uptake activity and Na,K-ATPase activity

  20. Enhancement of nisin, lysozyme, and monolaurin antimicrobial activities by ethylenediaminetetraacetic acid and lactoferrin.

    Science.gov (United States)

    Branen, Jill K; Davidson, P Michael

    2004-01-01

    A microtiter plate assay was employed to systematically assess the interaction between ethylenediaminetetraacetic acid (EDTA) or lactoferrin and nisin, lysozyme, or monolaurin against strains of Listeria monocytogenes, Escherichia coli, Salmonella enteritidis, and Pseudomonas fluorescens. Low levels of EDTA acted synergistically with nisin and lysozyme against L. monocytogenes but EDTA and monolaurin interacted additively against this microorganism. EDTA synergistically enhanced the activity of nisin, monolaurin, and lysozyme in tryptic soy broth (TSB) against two enterohemorrhagic E. coli strains. In addition, various combinations of nisin, lysozyme, and monolaurin with EDTA were bactericidal to some gram-negative bacteria whereas none of the antimicrobials alone were bactericidal. Lactoferrin alone (2000 microg ml(-1)) did not inhibit any of the bacterial strains, but did enhance nisin activity against both L. monocytogenes strains. Lactoferrin in combination with monolaurin inhibited growth of E. coli O157:H7 but not E. coli O104:H21. While lactoferrin combined with nisin or monolaurin did not completely inhibit growth of the gram-negative bacteria, there was some growth inhibition. All combinations of EDTA or lactoferrin with antimicrobials were less effective in 2% fat UHT milk than in TSB. S. enteritidis and P. fluorescens strains were consistently more resistant to antimicrobial combinations. Resistance may be due to differences in the outer membrane and/or LPS structure.

  1. Value addition in the efficacy of conventional antibiotics by Nisin against Salmonella.

    Directory of Open Access Journals (Sweden)

    Aman Preet Singh

    Full Text Available Frequent and indiscriminate use of existing battery of antibiotics has led to the development of multi drug resistant (MDR strains of pathogens. As decreasing the concentration of the antibiotic required to treat Salmonellosis might help in combating the development of resistant strains, the present study was designed to assess the synergistic effects, if any, of nisin, in combination with conventional anti-Salmonella antibiotics against Salmonella enterica serovar Typhimurium. Minimum inhibitory concentrations (MICs of the selected antimicrobial agents were determined by micro and macro broth dilution assays. In-vitro synergy between the agents was evaluated by radial diffusion assay, fractional inhibitory concentration (FIC index (checkerboard test and time-kill assay. Scanning electron microscopy (SEM was also performed to substantiate the effect of the combinations. In-vivo synergistic efficacy of the combinations selected on the basis of in-vitro results was also evaluated in the murine model, in terms of reduction in the number of Salmonellae in liver, spleen and intestine. Nisin-ampicillin and nisin-EDTA combinations were observed to have additive effects, whereas the combinations of nisin-ceftriaxone and nisin-cefotaxime were found to be highly synergistic against serovar Typhimurium as evident by checkerboard test and time-kill assay. SEM results revealed marked changes on the outer membrane of the bacterial cells treated with various combinations. In-vivo synergy was evident from the larger log unit decreases in all the target organs of mice treated with the combinations than in those treated with drugs alone. This study thus highlights that nisin has the potential to act in conjunction with conventional antibiotics at much lower MICs. These observations seem to be significant, as reducing the therapeutic concentrations of antibiotics may be a valuable strategy for avoiding/reducing the development of emerging antibiotic resistance

  2. Mechanisms of Drug Resistance: Daptomycin Resistance

    Science.gov (United States)

    Tran, Truc T.; Munita, Jose M.; Arias, Cesar A.

    2016-01-01

    Daptomycin (DAP) is a cyclic lipopeptide with in vitro activity against a variety of Gram-positive pathogens, including multidrug-resistant organisms. Since its introduction in clinical practice in 2003, DAP has become an important key front-line antibiotic for severe or deep-seated infections caused by Gram-positive organisms. Unfortunately, DAP-resistance (R) has been extensively documented in clinically important organisms such as Staphylococcus aureus, Enterococcus spp, and Streptococcus spp. Studies on the mechanisms of DAP-R in Bacillus subtilis and other Gram-positive bacteria indicate that the genetic pathways of DAP resistance are diverse and complex. However, a common phenomenon emerging from these mechanistic studies is that DAP-R is associated with important adaptive changes in cell wall and cell membrane homeostasis with critical changes in cell physiology. Findings related to these adaptive changes have offered novel insights into the genetics and molecular mechanisms of bacterial cell envelope stress response and the manner in which Gram-positive bacteria cope with the antimicrobial peptide attack and protect vital structures of the cell envelope such as the cell membrane. In this review, we will examine the most recent findings related to the molecular mechanisms of resistance to DAP in relevant Gram-positive pathogens and discuss the clinical implications for therapy against these important bacteria. PMID:26495887

  3. Enhancement Nisin Activity By Some Natural Additives

    International Nuclear Information System (INIS)

    Hussien, H.A.; El-Fouly, M.E.; Zayed, M.N.; Harroun, M.B.

    2010-01-01

    Nisin showed great inhibition of gram positive bacteria while it had no effect on gram negative bacteria or yeast.It is clear from the present study that 250ug/ml of nisin was lethal for S .aureus but this dose decreased to 25 ug/ml when combined with 0.05% of citric acid or 0.1% of lactic acid or 0.4% of cinnamon. Although nisin had no effect on P. aeruginosa but when 200ug/ml of nisin combined with 0.2% of citric acid or 0.1% of lactic acid or 2% of cinnamon P. aeruginosa completely inhibited.In the same manner 200ug/ml of nisin was sufficient to inhibit Debaryomyces sp. growth when combined by 3% of citric or 3.5% of lactic or 2% of cinnamon. On the other hand, 25 μg/ml of nisin reduced the following lethal concentrations of S .aureus from0.2% to 0.05%, 0.15% to 0.1% and from 1.2% to 0.4% for citric acid, lactic acid and cinnamon, respectively. While. 200 ug/ml of nisin decreased the following lethal concentrations of P. aeruginosa from 0.3% to 0.2%, 0.3% to 0.1% and from 4% to 2% for citric acid, lactic acid and cinnamon, respectively. Two hundred ug/ml of nisin decreased lethal concentrations of Debaryomyces sp. from4% to 3%, 4.5% to 3.5% for citric acid and lactic acid, respectively. Two hundred ug/ml of nisin did not reduce cinnamon lethal dose.

  4. Effect of nisin on biogenic amines and shelf life of vacuum packaged rainbow trout (Oncorhynchus mykiss) fillets.

    Science.gov (United States)

    Chaves López, Clemencia; Serio, Annalisa; Montalvo, Costanza; Ramirez, Cristina; Peréz Álvarez, José Angel; Paparella, Antonello; Mastrocola, Dino; Martuscelli, Maria

    2017-09-01

    Nisin is a lantibiotic exhibiting antimicrobial activity against a wide range of Gram-positive bacteria, or some Gram-negative bacteria when used in combination with other preservative agents. The objective of the present work was to study the effect of nisin treatment on biogenic amines occurrence and shelf life of refrigerated (4 °C) vacuum packaged rainbow trout samples. For this purpose samples were divided in two batches: the experimental batch (CB-N), consisting of samples immersed in sterilized broth formulated with soy milk 1.4% (v/v) and whey powder 11.2% (w/v) dissolved in deionized water with addition of nisin (500 mg L -1 ); the control batch (CB), consisting of samples immersed in the former broth without addition of nisin. A positive effect of nisin resulted on colour stability; in fact, the global colour index ΔE remained constant during the storage of treated rainbow trout samples, while it increased in the control. However, the behaviour of microbiota, texture, odour and biogenic amines were comparable between fillet samples treated with nisin broth and with control medium (without nisin). No inhibitory effects of nisin on biogenic amines accumulation was observed; conversely, the decline of histamine content (about 30%), observed only in fishes of the control batch, may be correlated to the presence of histamine-degradating bacteria ( Pseudomonas species). Further studies are necessary to investigate nisin action mechanism on the colour, an important physical characteristic involved in the product quality and consumer acceptability.

  5. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However, the underlying mechanism involved is still unclear. In searching for the cause of the mechanism, it has been found that palmitate inhibits insulin receptor (IR) gene expression, ...

  6. Effect of natamycin, nisin and glycerol on the physicochemical properties, roughness and hydrophobicity of tapioca starch edible films.

    Science.gov (United States)

    Ollé Resa, Carolina P; Jagus, Rosa J; Gerschenson, Lía N

    2014-07-01

    In this paper, films based on tapioca starch and containing nisin, natamycin and glycerol were characterized in relation to their physicochemical properties, roughness and hydrophobicity. The content of glycerol affected the mechanical properties of the films studied and the roughness and it was observed an increase in WVP with the increase in glycerol content. The addition of antimicrobials affected the mechanical properties, being nisin the one that produced the greater decrease in the Young modulus. The color was highly affected by the joint presence of natamycin and nisin, which increased the yellow index. The contact angle increased with antimicrobial addition indicating a decrease in hydrophilicity. Nisin also affected the roughness of the films. Water vapor permeability was slightly reduced by the presence of natamycin. It was observed that water vapor permeability and contact angle were correlated with the roughness of the films. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Nisin and its Antimicrobial Effect in Foods

    Directory of Open Access Journals (Sweden)

    Hamparsun Hampikyan

    2007-04-01

    Full Text Available Nisin is a bacteriocin which is produced by Lactococcus lactis and takes its place in I. class bacteriocins which are known as lantibiotics. Nisin has antimicrobial and bactericidal activity against a broad spectrum of gram positive bacteria and spores of Clostridium spp. and Bacillus spp. According to toxicity studies nisin is considered not toxic to humans. Its first established used was as a preservative in processed cheese products and since than numerous other applications in various foods such as meat and meat products, poultry products, sea products and beverages such as beer, wine have been used safely. In this review, the characteristics of nisin, its usage in food and its antimicrobial effect are considered. [TAF Prev Med Bull. 2007; 6(2: 142-147

  8. Nisin and its Antimicrobial Effect in Foods

    Directory of Open Access Journals (Sweden)

    Hamparsun Hampikyan

    2007-04-01

    Full Text Available Nisin is a bacteriocin which is produced by Lactococcus lactis and takes its place in I. class bacteriocins which are known as lantibiotics. Nisin has antimicrobial and bactericidal activity against a broad spectrum of gram positive bacteria and spores of Clostridium spp. and Bacillus spp. According to toxicity studies nisin is considered not toxic to humans. Its first established used was as a preservative in processed cheese products and since than numerous other applications in various foods such as meat and meat products, poultry products, sea products and beverages such as beer, wine have been used safely. In this review, the characteristics of nisin, its usage in food and its antimicrobial effect are considered. [TAF Prev Med Bull 2007; 6(2.000: 142-147

  9. Mechanisms of antidepressant resistance

    Directory of Open Access Journals (Sweden)

    Wissam eEl Hage

    2013-11-01

    Full Text Available Depression is one of the most frequent and severe mental disorder. Since the discovery of antidepressant properties of the imipramine and then after of other tricyclic compounds, several classes of psychotropic drugs have shown be effective in treating major depressive disorder. However, there is a wide range of variability in response to antidepressants that might lead to non response or partial response or in increased rate of relapse or recurrence. The mechanisms of response to antidepressant therapy are poorly understood, and few biomarkers are available than can predict response to pharmacotherapy. Here, we will first review markers that can be used to predict response to pharmacotherapy, such as markers of drug metabolism or blood-brain barrier function, the activity of specific brain areas or neurotransmitter systems, hormonal dysregulations or plasticity, and related molecular targets. We will describe both clinical and preclinical studies and describe factors that might affect the expression of these markers, including environmental or genetic factors and comorbidities. This information will permit us to suggest practical recommendations and innovative treatment strategies to improve therapeutic outcomes.

  10. The antimicrobial peptide nisin Z induces selective toxicity and apoptotic cell death in cultured melanoma cells.

    Science.gov (United States)

    Lewies, Angélique; Wentzel, Johannes Frederik; Miller, Hayley Christy; Du Plessis, Lissinda Hester

    2018-01-01

    Reprogramming of cellular metabolism is now considered one of the hallmarks of cancer. Most malignant cells present with altered energy metabolism which is associated with elevated reactive oxygen species (ROS) generation. This is also evident for melanoma, the leading cause of skin cancer related deaths. Altered mechanisms affecting mitochondrial bioenergetics pose attractive targets for novel anticancer therapies. Antimicrobial peptides have been shown to exhibit selective anticancer activities. In this study, the anti-melanoma potential of the antimicrobial peptide, nisin Z, was evaluated in vitro. Nisin Z was shown to induce selective toxicity in melanoma cells compared to non-malignant keratinocytes. Furthermore, nisin Z was shown to negatively affect the energy metabolism (glycolysis and mitochondrial respiration) of melanoma cells, increase reactive oxygen species generation and cause apoptosis. Results also indicate that nisin Z can decrease the invasion and proliferation of melanoma cells demonstrating its potential use against metastasis associated with melanoma. As nisin Z seems to place a considerable extra burden on the energy metabolism of melanoma cells, combination therapies with known anti-melanoma agents may be effective treatment options. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  11. Pathophysiological mechanisms of insulin resistance

    NARCIS (Netherlands)

    Brands, M.

    2013-01-01

    In this thesis we studied pathophysiological mechanisms of insulin resistance in different conditions in humans, i.e. in obesity, during lipid infusions, after hypercaloric feeding, and glucocorticoid treatment. We focused on 3 important hypotheses that are suggested to be implicated in the

  12. Increase of nisin production by Lactococcus lactis in different media ...

    African Journals Online (AJOL)

    Nisin production related to the growth conditions of Lactococcus lactis subsp. lactis ATCC 11454, the effects of various media components and concomitant release of nisin into the media, were studied through transfers (five times). Nisin production was assayed by agar diffusion using Lactobacillus sake ATCC 15521 as the ...

  13. Nisin Z Production by Lactococcus lactis subsp. cremoris WA2-67 of Aquatic Origin as a Defense Mechanism to Protect Rainbow Trout (Oncorhynchus mykiss, Walbaum) Against Lactococcus garvieae.

    Science.gov (United States)

    Araújo, Carlos; Muñoz-Atienza, Estefanía; Pérez-Sánchez, Tania; Poeta, Patrícia; Igrejas, Gilberto; Hernández, Pablo E; Herranz, Carmen; Ruiz-Zarzuela, Imanol; Cintas, Luis M

    2015-12-01

    Probiotics represent an alternative to chemotherapy and vaccination to control fish diseases, including lactococcosis caused by Lactococcus garvieae. The aims of this study were (i) to determine the in vitro probiotic properties of three bacteriocinogenic Lactococcus lactis subsp. cremoris of aquatic origin, (ii) to evaluate in vivo the ability of L. cremoris WA2-67 to protect rainbow trout (Oncorhynchus mykiss, Walbaum) against infection by L. garvieae, and (iii) to demonstrate the role of nisin Z (NisZ) production as an anti-infective mechanism. The three L. cremoris strains survived in freshwater at 18 °C for 7 days, withstood exposure to pH 3.0 and 10 % (v/v) rainbow trout bile, and showed different cell surface hydrophobicity (37.93-58.52 %). The wild-type NisZ-producer L. cremoris WA2-67 and its non-bacteriocinogenic mutant L. cremoris WA2-67 ∆nisZ were administered orally (10(6) CFU/g) to rainbow trout for 21 days and, subsequently, fish were challenged with L. garvieae CLG4 by the cohabitation method. The fish fed with the bacteriocinogenic strain L. cremoris WA2-67 reduced significantly (p trout against infection with the invasive pathogen L. garvieae and the relevance of NisZ production as an anti-infective mechanism. This is the first report demonstrating the effective in vivo role of LAB bacteriocin (NisZ) production as a mechanism to protect fish against bacterial infection. Our results suggest that the wild-type NisZ-producer strain L. cremoris WA2-67 could be used in fish farming to prevent lactococcosis in rainbow trout.

  14. Antimicrobial resistance mechanisms among Campylobacter.

    Science.gov (United States)

    Wieczorek, Kinga; Osek, Jacek

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed.

  15. Antimicrobial Resistance Mechanisms among Campylobacter

    Science.gov (United States)

    2013-01-01

    Campylobacter jejuni and Campylobacter coli are recognized as the most common causative agents of bacterial gastroenteritis in the world. Humans most often become infected by ingesting contaminated food, especially undercooked chicken, but also other sources of bacteria have been described. Campylobacteriosis is normally a self-limiting disease. Antimicrobial treatment is needed only in patients with more severe disease and in those who are immunologically compromised. The most common antimicrobial agents used in the treatment of Campylobacter infections are macrolides, such as erythromycin, and fluoroquinolones, such as ciprofloxacin. Tetracyclines have been suggested as an alternative choice in the treatment of clinical campylobacteriosis but in practice are not often used. However, during the past few decades an increasing number of resistant Campylobacter isolates have developed resistance to fluoroquinolones and other antimicrobials such as macrolides, aminoglycosides, and beta-lactams. Trends in antimicrobial resistance have shown a clear correlation between use of antibiotics in the veterinary medicine and animal production and resistant isolates of Campylobacter in humans. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter are discussed. PMID:23865047

  16. Enhancement of nisin production in milk by conjugal transfer of the protease-lactose plasmid pLP712 to the wild strain Lactococcus lactis UQ2

    OpenAIRE

    García-Parra, María D.; Campelo, Ana B.; García-Almendárez, Blanca E.; Regalado, Carlos; Rodríguez González, Ana; Martínez Fernández, Beatriz

    2010-01-01

    Lactococcus lactis UQ2 is a wild nisin A producer isolated from a Mexican cheese that grows poorly in milk. Conjugal matings with L. lactis NCDO712 to transfer the Lac+ Prt+ plasmid pLP712 and selection with nisin and lactose yielded L. lactis NCDO712 NisA+. Naturally rifampicin resistant L. lactis UQ2Rif was isolated to provide an additional selective marker. The identity of a transconjugant L. lactis UQ2Rif Lac+ was confirmed by RAPD-PCR fingerprinting, nisA PCR amplification, nisin product...

  17. Resistance mechanisms in Campylobacter jejuni

    Science.gov (United States)

    Iovine, Nicole M.

    2013-01-01

    Campylobacter jejuni is a major cause of food-borne gastroenteritis worldwide. While mortality is low, morbidity imparted by post-infectious sequelae such as Guillain-Barré syndrome, Reiter syndrome/reactive arthritis and irritable bowel syndrome is significant. In addition, the economic cost is high due to lost productivity. Food animals, particularly poultry, are the main reservoirs of C. jejuni. The over-use of antibiotics in the human population and in animal husbandry has led to an increase in antibiotic-resistant infections, particularly with fluoroquinolones. This is problematic because C. jejuni gastroenteritis is clinically indistinguishable from that caused by other bacterial pathogens, and such illnesses are usually treated empirically with fluoroquinolones. Since C. jejuni is naturally transformable, acquisition of additional genes imparting antibiotic resistance is likely. Therefore, an understanding of the antibiotic resistance mechanisms in C. jejuni is needed to provide proper therapy both to the veterinary and human populations. PMID:23406779

  18. Mechanisms of buffer therapy resistance.

    Science.gov (United States)

    Bailey, Kate M; Wojtkowiak, Jonathan W; Cornnell, Heather H; Ribeiro, Maria C; Balagurunathan, Yoganand; Hashim, Arig Ibrahim; Gillies, Robert J

    2014-04-01

    Many studies have shown that the acidity of solid tumors contributes to local invasion and metastasis. Oral pH buffers can specifically neutralize the acidic pH of tumors and reduce the incidence of local invasion and metastatic formation in multiple murine models. However, this effect is not universal as we have previously observed that metastasis is not inhibited by buffers in some tumor models, regardless of buffer used. B16-F10 (murine melanoma), LL/2 (murine lung) and HCT116 (human colon) tumors are resistant to treatment with lysine buffer therapy, whereas metastasis is potently inhibited by lysine buffers in MDA-MB-231 (human breast) and PC3M (human prostate) tumors. In the current work, we confirmed that sensitive cells utilized a pH-dependent mechanism for successful metastasis supported by a highly glycolytic phenotype that acidifies the local tumor microenvironment resulting in morphological changes. In contrast, buffer-resistant cell lines exhibited a pH-independent metastatic mechanism involving constitutive secretion of matrix degrading proteases without elevated glycolysis. These results have identified two distinct mechanisms of experimental metastasis, one of which is pH-dependent (buffer therapy sensitive cells) and one which is pH-independent (buffer therapy resistant cells). Further characterization of these models has potential for therapeutic benefit. Copyright © 2014 Neoplasia Press, Inc. Published by Elsevier Inc. All rights reserved.

  19. Mechanism of ciprofloxacin resistance in Shigella dysenteriae ...

    African Journals Online (AJOL)

    Bacterial resistance to quinolones has emerged rapidly and such resistance has traditionally been attributed to the chromosomally mediated mechanisms that alter the quinolone targets and/or overproduce multidrug resistance efflux pumps. In the present investigation possible mechanism of ciprofloxacin (Cp) resistance in ...

  20. Intrinsic and acquired resistance mechanisms in enterococcus

    Science.gov (United States)

    Hollenbeck, Brian L.; Rice, Louis B.

    2012-01-01

    Enterococci have the potential for resistance to virtually all clinically useful antibiotics. Their emergence as important nosocomial pathogens has coincided with increased expression of antimicrobial resistance by members of the genus. The mechanisms underlying antibiotic resistance in enterococci may be intrinsic to the species or acquired through mutation of intrinsic genes or horizontal exchange of genetic material encoding resistance determinants. This paper reviews the antibiotic resistance mechanisms in Enterococcus faecium and Enterococcus faecalis and discusses treatment options. PMID:23076243

  1. Antimicrobial behavior of phage endolysin PlyP100 and its synergy with nisin to control Listeria monocytogenes in Queso Fresco.

    Science.gov (United States)

    Ibarra-Sánchez, Luis A; Van Tassell, Maxwell L; Miller, Michael J

    2018-06-01

    Hispanic-style fresh cheeses, such as Queso Fresco (QF), have been linked to numerous listeriosis outbreaks in the United States. In this work, we have studied the antilisterial behavior and effectiveness of the Listeria phage endolysin PlyP100 in QF, as well as the potential synergy between PlyP100 and nisin. PlyP100 showed similar bacterial reduction regardless of varying L. monocytogenes inoculum size in QF, and when the inoculation size was 1 Log CFU/g, no pathogen recovery after cheese enrichment was observed. PlyP100 was stable in QF for up to 28 days of cold storage exhibiting similar antilisterial activity regardless of when contamination with L. monocytogenes occurred. PlyP100 alone exhibited a strong listeriostatic effect in QF, on the contrary, nisin alone was not effective to control the pathogen in QF during cold storage. The combination of nisin and PlyP100 showed a strong synergy in QF with non-enumerable levels of L. monocytogenes after 4 weeks of refrigerated storage. Moreover, L. monocytogenes isolates from cheeses treated with nisin, PlyP100, and their combination did not develop resistance to nisin or PlyP100. Our results support the use of PlyP100 combined with nisin as an efficient L. monocytogenes control measure in QF. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. The presence of modifiable residues in the core peptide part of precursor nisin is not crucial for precursor nisin interactions with NisB- and NisC.

    Directory of Open Access Journals (Sweden)

    Rustem Khusainov

    Full Text Available Precursor nisin is a model posttranslationally modified precursor lantibiotic that can be structurally divided into a leader peptide sequence and a modifiable core peptide part. The nisin core peptide clearly plays an important role in the precursor nisin-nisin modification enzymes interactions, since it has previously been shown that the construct containing only the nisin leader sequence is not sufficient to pull-down the nisin modification enzymes NisB and NisC. Serines and threonines in the core peptide part are the residues that NisB specifically dehydrates, and cysteines are the residues that NisC stereospecifically couples to the dehydrated amino acids. Here, we demonstrate that increasing the number of negatively charged residues in the core peptide part of precursor nisin, which are absent in wild-type nisin, does not abolish binding of precursor nisin to the modification enzymes NisB and NisC, but dramatically decreases the antimicrobial potency of these nisin mutants. An unnatural precursor nisin variant lacking all serines and threonines in the core peptide part and an unnatural precursor nisin variant lacking all cysteines in the core peptide part still bind the nisin modification enzymes NisB and NisC, suggesting that these residues are not essential for direct interactions with the nisin modification enzymes NisB and NisC. These results are important for lantibiotic engineering studies.

  3. Cloning of nis gene and Nisin purification from Lactococcus lactis ...

    African Journals Online (AJOL)

    The purified nisin by chloroform extraction was analyzed on 20% SDS-PAGE and gave sharp band at ~ 3.4 kDa. The 3 dimension structure of the purified Nisin was studied by CPHModels as pdb with chimera program. Keywords: Lactococcus lactis, nis cloning, 16S rRNA, chloroform extraction and SDS-PAGE

  4. Short Communication A study on the bactericidal effect of nisin ...

    African Journals Online (AJOL)

    Nisin, the best known LAB (Lactic Acid Bacteria) bacteriocin, is a promising alternative to antibiotics, and displays a broad spectrum of activity against a wide range of spoilage and pathogenic Gram positive bacteria. The aim of the study was to determine the bactericidal effect of nisin. The Lactococcus lactis MTCC 440 used ...

  5. Structure and biological activity of chemically modified nisin A species

    NARCIS (Netherlands)

    Rollema, Harry S.; Metzger, Jörg W.; Both, Paula; Kuipers, Oscar P.; Siezen, Roland J.

    1996-01-01

    Nisin, a 34-residue peptide bacteriocin, contains the less common amino acids lanthionine, β-methyllanthionine, dehydroalanine (Dha), and dehydrobutyrine (Dhb). Several chemically modified nisin A species were purified by reverse-phase HPLC and characterized by two-dimensional NMR and electrospray

  6. Some chemical properties of nisin produced by lactococcus lactis

    International Nuclear Information System (INIS)

    Hussein, H.; Abdel Karem, H.; El-Hadedy, D.; Badr, S.

    2010-01-01

    The present study was carried out to study the properties of nisin produced by lactococcus lactis FG 2 isolated from local un fated cheese. The maximum anti-microbial effect of pure nisin was occurred at ph 6 and 7. Nisin was heat stable from 40 to 90 degree C for 30 min. Molecular weight of nisin was determined by SDS-PAGE, it was 3.0 kDa and after irradiated the microbial cells to 1.5 kGy dose level the molecular weight increased to 3.5 t kDa then decreased at 2 kGy . Storage for two weeks it appeared in dimmer means and had a molecular weight 7 kDa . Using amino acid analyzer reveled that nisin contained a majority of nonpolar amino acids and exhibited cystine in composition . Nisin produced in whey have higher activity than nisin produced in MRS medium but both had the same structure. The results proved that nisin gene is in coded in chromosome and not with plasmid.

  7. Bioenergetic consequences of nisin combined with carvacrol towards Bacillus cereus

    NARCIS (Netherlands)

    Pol, I.E.; Krommer, J.; Smid, E.J.

    2002-01-01

    This paper describes the influence of a combination of nisin and carvacrol on the membrane potential, the pH gradient and the intracellular ATP pools of vegetative cells of Bacillus cereus. Both the membrane potential and the pH gradient were dissipated by nisin and carvacrol. The intracellular ATP

  8. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    independent phosphorylation of PKCε causes this reduction in insulin receptor gene expression. One of the pathways through which fatty acid can induce insulin resistance in insulin target cells is suggested by these studies. We provide an overview of ...

  9. Synergy of a combination of nisin and citric acid against Staphylococcus aureus and Listeria monocytogenes.

    Science.gov (United States)

    Zhao, Xingchen; Zhen, Zhen; Wang, Xinyang; Guo, Na

    2017-12-01

    Food-borne diseases caused by pathogens, such as Staphylococcus aureus and Listeria monocytogenes, have long attracted attention globally from researchers, food industries, and food safety authorities. Nisin (NS) is the only bacteriocin used worldwide as a generally recognised as safe (GRAS) food preservative, while citric acid (CA) has an unrestricted use in foods since it has GRAS status. In this study, synergistic interactions of NS combined with CA against S. aureus and L. monocytogenes were studied by the chequerboard microdilution method, with fractional inhibitory concentration index values ranging from 0.25 to 0.375 and 0.19 to 0.375, respectively. The positive interactions were verified by time-kill studies in pasteurised milk and disk diffusion assays. The mechanism of the synergistic antibacterial of NS and CA is proposed following SEM analysis and the determination of release of cell constituents. These results suggest that the cell walls and membrane are the probable main targets of this antimicrobial combination. These findings indicated that the combination of NS and CA not only could be used as a new promising naturally sourced food preservative, but may also reduce the problem of bacterial resistance.

  10. First resistance mechanisms characterization in glyphosate-resistant Leptochloa virgata.

    Directory of Open Access Journals (Sweden)

    Ricardo Alcántara-de la Cruz

    2016-11-01

    Full Text Available Leptochloa virgata (L. P. Beauv. is an annual weed common in citrus groves in the states of Puebla and Veracruz, Mexico limiting their production. Since 2010, several L. virgata populations were identified as being resistant to glyphosate, but studies of their resistance mechanisms developed by this species have been conducted. In this work, three glyphosate-resistant populations (R8, R14 and R15 collected in citrus orchards from Mexico, were used to study their resistance mechanisms comparing them to one susceptible population (S. Dose-response and shikimic acid accumulation assays confirmed the glyphosate resistance of the three resistant populations. Higher doses of up to 720 g ae ha-1 (field dose were needed to control by 50% plants of resistant populations. The S population absorbed between 7 and 13% more 14C-glyphosate than resistant ones, and translocated up to 32.2% of 14C-glyphosate to the roots at 96 h after treatment (HAT. The R8, R14 and R15 populations translocated only 24.5, 26.5 and 21.9%, respectively. The enzyme activity of 5-enolpyruvyl shikimate-3-phosphate synthase (EPSPS was not different in the S, R8 and R14 populations. The R15 Population exhibited 165.9 times greater EPSPS activity. Additionally, this population showed a higher EPSPS basal activity and a substitution in the codon 106 from Proline to Serine in the EPSPS protein sequence. EPSPS gene expression in the R15 population was similar to that of S population. In conclusion, the three resistant L. virgata populations show reduced absorption and translocation of 14C-glyphosate. Moreover, a mutation and an enhanced EPSPS basal activity at target-site level confers higher resistance to glyphosate. These results describe for the first time the glyphosate resistance mechanisms developed by resistant L. virgata populations of citrus orchards from Mexico.

  11. Bedaquiline resistance: Its emergence, mechanism and prevention.

    Science.gov (United States)

    Nguyen, Thi Van Anh; Anthony, Richard M; Bañuls, Anne-Laure; Vu, Dinh Hoa; Alffenaar, Jan-Willem C

    2017-11-08

    Bedaquiline, a new anti-tuberculosis drug, has already been used in more than 50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This paper aims to review currently identified mechanisms of resistance, the emergence of bedaquiline resistance, and discuss strategies to delay the resistance acquisition. In vitro and clinical studies as well as reports from the compassionate use have identified the threat of bedaquiline resistance and cross-resistance with clofazimine, emphasizing the crucial need for the systematic surveillance of resistance. Currently known mechanisms of resistance include mutations within the atpE, Rv0678 and pepQ genes. The development of standardized drug susceptibility testing (DST) for bedaquiline is urgently needed.Understanding any target and non-target based mechanisms is essential to minimize the resistance development and treatment failure, help to develop appropriate DST for bedaquiline and genetic based resistance screening. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  12. Molecular mechanism of insulin resistance

    Indian Academy of Sciences (India)

    PRAKASH

    Free fatty acids are known to play a key role in promoting loss of insulin sensitivity, thereby causing insulin resistance and type 2 diabetes. However ... PDK1-independent phosphorylation of PKCε causes this reduction in insulin receptor gene ... i.e. muscle, liver and fat, is extremely high (Brunetti et al 2001). However, there ...

  13. Molecular mechanisms of insulin resistance

    African Journals Online (AJOL)

    This review discusses recent advances in understanding of the structure and function of the insulin receptor and insulin action, and how these relate to the clinical aspects of insulin resistance associated with non-insulin-dependent diabetes and other disorders. Improved understanding of the molecular basis of insulin ...

  14. Bedaquiline resistance: Its emergence, mechanism and prevention.

    NARCIS (Netherlands)

    Nguyen, Thi Van Anh; Anthony, Richard M; Bañuls, Anne-Laure; Vu, Dinh Hoa; Alffenaar, Jan-Willem C

    2017-01-01

    Bedaquiline, a new anti-tuberculosis drug, has already been used in more than 50 countries. The emergence of bedaquiline resistance is alarming, as it may result in the rapid loss of this new drug. This paper aims to review currently identified mechanisms of resistance, the emergence of bedaquiline

  15. [Resistance mechanisms and cross-resistance of phoxim-resistant Frankliniella occidentalis Pergande population].

    Science.gov (United States)

    Wang, Sheng-Yin; Zhou, Xian-Hong; Zhang, An-Sheng; Li, Li-Li; Men, Xing-Yuan; Zhang, Si-Cong; Liu, Yong-Jie; Yu, Yi

    2012-07-01

    To understand the resistance risks of Frankliniella occidentalis Pergande against phoxim, this paper studied the resistance mechanisms of phoxim-resistant F. occidentalis population against phoxim and the cross-resistance of the population against other insecticides. The phoxim-resistant population had medium level cross-resistance to chlorpyrifos, lambda-cyhalothrin, and methomyl, low level cross-resistance to chlorfenapyr, imidacloprid, emamectin-benzoate, and spinosad, but no cross-resistance to acetamiprid and abamectin. The synergists piperonyl butoxide (PBO), s, s, s-tributyl phosphorotrithioate (DEF), and triphenyl phosphate (TPP) had significant synergism (P occidentalis could play an important role in the resistance of the plant against phoxim.

  16. Preparation of extra-small nisin nanoparticles for enhanced antibacterial activity after autoclave treatment.

    Science.gov (United States)

    Chang, Ranran; Lu, Hao; Li, Man; Zhang, Shuangling; Xiong, Liu; Sun, Qingjie

    2018-04-15

    Nisin is applied broadly in the food industry as an antimicrobial peptide. The objective of this study is to prepare nisin nanoparticles using free nisin by a facile nanoprecipitation technique and to investigate their antimicrobial activity after high-temperature processing. Transmission electron microscopic images showed that the size of extra-small nisin nanoparticles with different initial concentrations of nisin (0.1%, 0.3% and 0.5%) was 5, 10 and 15 nm, respectively. The nisin nanoparticles were stable at pH 5.0 with the smallest size. Moreover, nisin nanoparticles exhibited a higher antimicrobial activity than free nisin at a concentration below 2.0 mg/ml after autoclave treatment. These results suggested that nisin nanoparticles could serve as a potential food preservative. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis.

    Science.gov (United States)

    Zhang, Yu-jiao; Li, Xiao-jing; Mi, Kai-xia

    2016-10-20

    Tuberculosis, caused by the pathogen Mycobacterium tuberculosis, is one of the world's deadliest bacterial infectious disease. It is still a global-health threat, particularly because of the drug-resistant forms. Fluoroquinolones, with target of gyrase, are among the drugs used to treat tuberculosis. However, their widespread use has led to bacterial resistance. The molecular mechanisms of fluoroquinolone resistance in mycobacterium tuberculosis have been reported, such as DNA gyrase mutations, drug efflux pumps system, bacterial cell wall thickness and pentapeptide proteins (MfpA) mediated regulation of gyrase. Mutations in gyrase conferring quinolone resistance play important roles and have been extensively studied. Recent studies have shown that the regulation of DNA gyrase affects mycobacterial drug resistance, but the mechanisms, especially by post-translational modification and regulatory proteins, are poorly understood. In this review, we summarize the fluoroquinolone drug development, and the molecular genetics of fluoroquinolone resistance in mycobacteria. Comprehensive understanding of the mechanisms of fluoroquinolone resistance in Mycobacterium tuberculosis will open a new view on understanding drug resistance in mycobacteria and lead to novel strategies to develop new accurate diagnosis methods.

  18. Mechanisms of antibiotic resistance in enterococci

    Science.gov (United States)

    Miller, William R; Munita, Jose M; Arias, Cesar A

    2015-01-01

    Multidrug-resistant (MDR) enterococci are important nosocomial pathogens and a growing clinical challenge. These organisms have developed resistance to virtually all antimicrobials currently used in clinical practice using a diverse number of genetic strategies. Due to this ability to recruit antibiotic resistance determinants, MDR enterococci display a wide repertoire of antibiotic resistance mechanisms including modification of drug targets, inactivation of therapeutic agents, overexpression of efflux pumps and a sophisticated cell envelope adaptive response that promotes survival in the human host and the nosocomial environment. MDR enterococci are well adapted to survive in the gastrointestinal tract and can become the dominant flora under antibiotic pressure, predisposing the severely ill and immunocompromised patient to invasive infections. A thorough understanding of the mechanisms underlying antibiotic resistance in enterococci is the first step for devising strategies to control the spread of these organisms and potentially establish novel therapeutic approaches. PMID:25199988

  19. Mechanisms of Candida biofilm drug resistance

    Science.gov (United States)

    Taff, Heather T; Mitchell, Kaitlin F; Edward, Jessica A; Andes, David R

    2013-01-01

    Candida commonly adheres to implanted medical devices, growing as a resilient biofilm capable of withstanding extraordinarily high antifungal concentrations. As currently available antifungals have minimal activity against biofilms, new drugs to treat these recalcitrant infections are urgently needed. Recent investigations have begun to shed light on the mechanisms behind the profound resistance associated with the biofilm mode of growth. This resistance appears to be multifactorial, involving both mechanisms similar to conventional, planktonic antifungal resistance, such as increased efflux pump activity, as well as mechanisms specific to the biofilm lifestyle. A unique biofilm property is the production of an extracellular matrix. Two components of this material, β-glucan and extracellular DNA, promote biofilm resistance to multiple antifungals. Biofilm formation also engages several stress response pathways that impair the activity of azole drugs. Resistance within a biofilm is often heterogeneous, with the development of a subpopulation of resistant persister cells. In this article we review the molecular mechanisms underlying Candida biofilm antifungal resistance and their relative contributions during various growth phases. PMID:24059922

  20. Correlation of molecular resistance mechanisms and phenotypic resistance levels in streptomycin-resistant Mycobacterium tuberculosis.

    OpenAIRE

    Meier, A; Sander, P; Schaper, K J; Scholz, M; Böttger, E C

    1996-01-01

    Quantitative susceptibility testing of clinical isolates of streptomycin-resistant Mycobacterium tuberculosis demonstrated that there is a close correlation between the molecular resistance mechanism and the in vitro activity of streptomycin: mutations in rpsL were mainly associated with high-level resistance, mutations in rrs were associated with an intermediate level of resistance, and streptomycin-resistant isolates with wild-type rpsL and rrs exhibited a low-level resistance phenotype. In...

  1. Mechanisms of insulin resistance in obesity

    Science.gov (United States)

    Ye, Jianping

    2014-01-01

    Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

  2. Mechanisms of Resistance to Photodynamic Therapy

    Science.gov (United States)

    Casas, Adriana; Di Venosa, Gabriela; Hasan, Tayyaba; Batlle, Alcira

    2013-01-01

    Photodynamic therapy (PDT) involves the administration of a photosensitizer (PS) followed by illumination with visible light, leading to generation of reactive oxygen species. The mechanisms of resistance to PDT ascribed to the PS may be shared with the general mechanisms of drug resistance, and are related to altered drug uptake and efflux rates or altered intracellular trafficking. As a second step, an increased inactivation of oxygen reactive species is also associated to PDT resistance via antioxidant detoxifying enzymes and activation of heat shock proteins. Induction of stress response genes also occurs after PDT, resulting in modulation of proliferation, cell detachment and inducing survival pathways among other multiple extracellular signalling events. In addition, an increased repair of induced damage to proteins, membranes and occasionally to DNA may happen. PDT-induced tissue hypoxia as a result of vascular damage and photochemical oxygen consumption may also contribute to the appearance of resistant cells. The structure of the PS is believed to be a key point in the development of resistance, being probably related to its particular subcellular localization. Although most of the features have already been described for chemoresistance, in many cases, no cross-resistance between PDT and chemotherapy has been reported. These findings are in line with the enhancement of PDT efficacy by combination with chemotherapy. The study of cross resistance in cells with developed resistance against a particular PS challenged against other PS is also highly complex and comprises different mechanisms. In this review we will classify the different features observed in PDT resistance, leading to a comparison with the mechanisms most commonly found in chemo resistant cells. PMID:21568910

  3. Effect of Co-overexpression of Nisin Key Genes on Nisin Production Improvement in Lactococcus lactis LS01.

    Science.gov (United States)

    Ni, Zhi-Jian; Zhang, Xiao-Yuan; Liu, Fei; Wang, Miao; Hao, Rong-Hua; Ling, Pei-Xue; Zhu, Xi-Qiang

    2017-06-01

    Nisin is a small antimicrobial peptide produced by several subset strains of Lactococcus lactis. To improve nisin yield in the producer L. lactis LS01, we proposed a successive fusion of nisA with nisRK and nisFEG into a single shuttle expression vector pMG36e under the control of the native strong constitutive promoter p32. Subsequently, the recombinant vectors were transplanted into the producer cell through electroporation. Nisin productivity was determined through sodium dodecyl sulfate-polyacrylamide gel electrophoresis and bioactivity assays. Expression of nisin peptide was detected by agar diffusion bioassay, and the transcriptional levels of the target genes involved in nisin biosynthesis were investigated via semi-quantitative reverse transcription PCR expression analysis using 16S ribosomal RNA (rRNA) as an internal control. Results suggested that the introduction of empty plasmid did not affect nisin production of L. lactis LS01, whereas by our rational construction and screening, the engineered strain co-overexpressing nisA, nisRK, and nisFEG achieved a maximum increment in bioactive nisin production with a yield of 2470 IU/ml in shake flasks and 4857 IU/ml in 1.0-l fermenters, which increased by approximately 66.3 and 52.6% (P < 0.05), respectively, compared with that of the original strain under the given fermentation conditions. Meanwhile, the transcriptional analysis revealed that the expression of most of these multicopy genes except nisE at transcriptional level were upregulated in the two recombinant strains (LS01/pAR and LS01/pARF), possibly contributing to the improved nisin production. Therefore, this study would provide a potential strategy to improve the economic benefits of nisin manufacture for large-scale industrial production.

  4. Intensive mutagenesis of the nisin hinge leads to the rational design of enhanced derivatives.

    Directory of Open Access Journals (Sweden)

    Brian Healy

    Full Text Available Nisin A is the most extensively studied lantibiotic and has been used as a preservative by the food industry since 1953. This 34 amino acid peptide contains three dehydrated amino acids and five thioether rings. These rings, resulting from one lanthionine and four methyllanthionine bridges, confer the peptide with its unique structure. Nisin A has two mechanisms of action, with the N-terminal domain of the peptide inhibiting cell wall synthesis through lipid II binding and the C-terminal domain responsible for pore-formation. The focus of this study is the three amino acid 'hinge' region (N 20, M 21 and K 22 which separates these two domains and allows for conformational flexibility. As all lantibiotics are gene encoded, novel variants can be generated through manipulation of the corresponding gene. A number of derivatives in which the hinge region was altered have previously been shown to possess enhanced antimicrobial activity. Here we take this approach further by employing simultaneous, indiscriminate site-saturation mutagenesis of all three hinge residues to create a novel bank of nisin derivative producers. Screening of this bank revealed that producers of peptides with hinge regions consisting of AAK, NAI and SLS displayed enhanced bioactivity against a variety of targets. These and other results suggested a preference for small, chiral amino acids within the hinge region, leading to the design and creation of producers of peptides with hinges consisting of AAA and SAA. These producers, and the corresponding peptides, exhibited enhanced bioactivity against Lactococcus lactis HP, Streptococcus agalactiae ATCC 13813, Mycobacterium smegmatis MC2155 and Staphylococcus aureus RF122 and thus represent the first example of nisin derivatives that possess enhanced activity as a consequence of rational design.

  5. Mechanisms of bacterial resistance to antimicrobial agents.

    NARCIS (Netherlands)

    van Duijkeren, Engeline; Schink, Anne-Kathrin; Roberts, Marilyn C; Wang, Yang; Schwarz, Stefan

    During the past decades resistance to virtually all antimicrobial agents has been observed in bacteria of animal origin. This chapter describes in detail the mechanisms so far encountered for the various classes of antimicrobial agents. The main mechanisms include enzymatic inactivation by either

  6. Mechanisms of resistance to paraquat in plants.

    Science.gov (United States)

    Hawkes, Timothy R

    2014-09-01

    The aim of this brief review is to draw information from studies of the mechanism of evolved resistance in weeds, together with information from laboratory studies of paraquat tolerance in model plants. Plants having mutations that limit paraquat uptake into cytoplasm, that confer various stress tolerances or that have transgenes that co-express two or more of the chloroplast Halliwell-Asada cycle enzymes can all exhibit enhanced tolerance to paraquat. However, none of these mechanisms correspond to the high-level resistances that have evolved naturally in weeds. Most, but not all, of the evidence from studies of paraquat-resistant biotypes of weeds can reasonably be reconciled with the proposal of a single major gene mechanism that sequesters paraquat away from chloroplasts and into the vacuole. However, the molecular details of this putative mechanism remain ill-defined. © 2013 Society of Chemical Industry.

  7. Mechanisms of polymyxin resistance: acquired and intrinsic resistance in bacteria

    Directory of Open Access Journals (Sweden)

    Abiola Olumuyiwa Olaitan

    2014-11-01

    Full Text Available Polymyxins are polycationic antimicrobial peptides that are currently the last-resort antibiotics for the treatment of multidrug-resistant, Gram-negative bacterial infections. The reintroduction of polymyxins for antimicrobial therapy has been followed by an increase in reports of resistance among Gram-negative bacteria. Some bacteria, such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii, develop resistance to polymyxins in a process referred to as acquired resistance, whereas other bacteria, such as Proteus spp., Serratia spp. and Burkholderia spp., are naturally resistant to these drugs. Reports of polymyxin resistance in clinical isolates have recently increased, including acquired and intrinsically resistant pathogens. This increase is considered a serious issue, prompting concern due to the low number of currently available effective antibiotics. This review summarizes current knowledge concerning the different strategies bacteria employ to resist the activities of polymyxins.Gram-negative bacteria employ several strategies to protect themselves from polymyxin antibiotics (polymyxin B and colistin, including a variety of lipopolysaccharide (LPS modifications, such as modifications of lipid A with phosphoethanolamine and 4-amino-4-deoxy-L-arabinose, in addition to the use of efflux pumps, the formation of capsules and overexpression of the outer membrane protein OprH, which are all effectively regulated at the molecular level. The increased understanding of these mechanisms is extremely vital and timely to facilitate studies of antimicrobial peptides and find new potential drugs targeting clinically relevant Gram-negative bacteria.

  8. The antimicrobial effect of Origanum compactum essential oil, nisin ...

    African Journals Online (AJOL)

    The antimicrobial effect of Origanum compactum essential oil, nisin and their combination against Escherichia coli in tryptic soy broth (TSB) and in sheep natural sausage casings during storage at 25 and 7°C.

  9. Nisin Production Utilizing Skimmed Milk Aiming to Reduce Process Cost

    Science.gov (United States)

    Jozala, Angela Faustino; de Andrade, Maura Sayuri; de Arauz, Luciana Juncioni; Pessoa, Adalberto; Penna, Thereza Christina Vessoni

    Nisin is a natural additive for conservation of food, pharmaceutical, and dental products and can be used as a therapeutic agent. Nisin inhibits the outgrowth of spores, the growth of a variety of Gram-positive and Gram-negative bacteria. This study was performed to optimize large-scale nisin production in skimmed milk and subproducts aiming at low-costs process and stimulating its utilization. Lactococcus lactis American Type Culture Collection (ATCC) 11454 was developed in a rotary shaker (30°C/36 h/100 rpm) in diluted skimmed milk and nisin activity, growth parameters, and media components were also studied. Nisin activity in growth media was expressed in arbitrary units (AU/mL) and converted to standard nisin concentration (Nisaplin®, 25 mg of pure nisin is 1.0×106 AU/mL). Nisin activity in skimmed milk 2.27 gtotal solids was up to threefold higher than transfers in skimmed milk 4.54 gtotal solids and was up to 85-fold higher than transfers in skimmed milk 1.14 gtotal solids. L. lactis was assayed in a New Brunswick fermentor with 1.5 L of diluted skimmed milk (2.27 gtotal solids) and airflow of 1.5 mL/min (30°C/36/200 rpm), without pH control. In this condition nisin activity was observed after 4 h (45.07 AU/mL) and in the end of 36 h process (3312.07 AU/mL). This work shows the utilization of a low-cost growth medium (diluted skimmed milk) to nisin production with wide applications. Furthermore, milk subproducts (milk whey) can be exploited in nisin production, because in Brazil 50% of milk whey is disposed with no treatment in rivers and because of high organic matter concentrations it is considered an important pollutant. In this particular case an optimized production of an antimicrobial would be lined up with industrial disposal recycling.

  10. Antibiotic resistance mechanisms of Vibrio cholerae.

    Science.gov (United States)

    Kitaoka, Maya; Miyata, Sarah T; Unterweger, Daniel; Pukatzki, Stefan

    2011-04-01

    As the causative agent of cholera, the bacterium Vibrio cholerae represents an enormous public health burden, especially in developing countries around the world. Cholera is a self-limiting illness; however, antibiotics are commonly administered as part of the treatment regimen. Here we review the initial identification and subsequent evolution of antibiotic-resistant strains of V. cholerae. Antibiotic resistance mechanisms, including efflux pumps, spontaneous chromosomal mutation, conjugative plasmids, SXT elements and integrons, are also discussed. Numerous multidrug-resistant strains of V. cholerae have been isolated from both clinical and environmental settings, indicating that antibiotic use has to be restricted and alternative methods for treating cholera have to be implemented.

  11. Mechanisms of resistance to immune checkpoint inhibitors.

    Science.gov (United States)

    Jenkins, Russell W; Barbie, David A; Flaherty, Keith T

    2018-01-01

    Immune checkpoint inhibitors (ICI) targeting CTLA-4 and the PD-1/PD-L1 axis have shown unprecedented clinical activity in several types of cancer and are rapidly transforming the practice of medical oncology. Whereas cytotoxic chemotherapy and small molecule inhibitors ('targeted therapies') largely act on cancer cells directly, immune checkpoint inhibitors reinvigorate anti-tumour immune responses by disrupting co-inhibitory T-cell signalling. While resistance routinely develops in patients treated with conventional cancer therapies and targeted therapies, durable responses suggestive of long-lasting immunologic memory are commonly seen in large subsets of patients treated with ICI. However, initial response appears to be a binary event, with most non-responders to single-agent ICI therapy progressing at a rate consistent with the natural history of disease. In addition, late relapses are now emerging with longer follow-up of clinical trial populations, suggesting the emergence of acquired resistance. As robust biomarkers to predict clinical response and/or resistance remain elusive, the mechanisms underlying innate (primary) and acquired (secondary) resistance are largely inferred from pre-clinical studies and correlative clinical data. Improved understanding of molecular and immunologic mechanisms of ICI response (and resistance) may not only identify novel predictive and/or prognostic biomarkers, but also ultimately guide optimal combination/sequencing of ICI therapy in the clinic. Here we review the emerging clinical and pre-clinical data identifying novel mechanisms of innate and acquired resistance to immune checkpoint inhibition.

  12. Mechanisms of resistance to alkylating agents

    OpenAIRE

    Damia, G.; D‘Incalci, M.

    1998-01-01

    Alkylating agents are the most widely used anticancer drugs whose main target is the DNA, although how exactly the DNA lesions cause cell death is still not clear. The emergence of resistance to this class of drugs as well as to other antitumor agents is one of the major causes of failure of cancer treatment. This paper reviews some of the best characterized mechanisms of resistance to alkylating agents. Pre- and post-target mechanisms are recognized, the former able to limit the formation of...

  13. Microemulsions as Potential Carriers of Nisin

    DEFF Research Database (Denmark)

    Chatzidaki, Maria D; Papadimitriou, Konstantinos; Alexandraki, Voula

    2016-01-01

    in an increase in the micellar size due to the penetration of water into the hydrophilic core of the inverse swollen micelles (hydration-induced swelling behavior). The dynamic properties of the surfactant monolayer were also affected by the nature of the used vegetable oil, the ethanol content, and the presence......Water-in-oil (W/O) microemulsions based on either refined olive oil (ROO) or sunflower oil (SO), distilled monoglycerides (DMG), and ethanol were used as nisin carriers in order to ensure its effectiveness as a biopreservative. This work presents experimental evidence on the effects of ethanol....... Modeling of representative SAXS profiles was applied to gain further insight into the effects of ethanol and solubilized water content on the inverse swollen micelles' size and morphology. With increasing ethanol content, the overall size of the inverse micelles decreased, whereas hydration resulted...

  14. Physiochemical parameters optimization for enhanced nisin production by Lactococcus lactis (MTCC 440

    Directory of Open Access Journals (Sweden)

    Puspadhwaja Mall

    2010-02-01

    Full Text Available The influence of various physiochemical parameters on the growth of Lactococcus lactis sub sp. lactis MTCC 440 was studied at shake flask level for 20 h. Media optimization (MRS broth was studied to achieve enhanced growth of the organism and also nisin production. Bioassay of nisin was done with agar diffusion method using Streptococcus agalactae NCIM 2401 as indicator strain. MRS broth (6%, w/v with 0.15μg/ml of nisin supplemented with 0.5% (v/v skimmed milk was found to be the best for nisin production as well as for growth of L lactis. The production of nisin was strongly influenced by the presence of skimmed milk and nisin in MRS broth. The production of nisin was affected by the physical parameters and maximum nisin production was at 30(0C while the optimal temperature for biomass production was 37(0C.

  15. Antimicrobial Effect of Nisin against Bacillus cereus in Beef Jerky during Storage.

    Science.gov (United States)

    Lee, Na-Kyoung; Kim, Hyoun Wook; Lee, Joo Yeon; Ahn, Dong Uk; Kim, Cheon-Jei; Paik, Hyun-Dong

    2015-01-01

    The microbial distribution of raw materials and beef jerky, and the effect of nisin on the growth of Bacillus cereus inoculated in beef jerky during storage, were studied. Five strains of pathogenic B. cereus were detected in beef jerky, and identified with 99.8% agreement using API CHB 50 kit. To evaluate the effect of nisin, beef jerky was inoculated with approximately 3 Log CFU/g of B. cereus mixed culture and nisin (100 IU/g and 500 IU/g). During the storage of beef jerky without nisin, the number of mesophilic bacteria and B. cereus increased unlikely for beef jerky with nisin. B. cereus started to grow after 3 d in 100 IU nisin/g treatment, and after 21 d in 500 IU nisin/g treatment. The results suggest that nisin could be an effective approach to extend the shelf-life, and improve the microbial safety of beef jerky, during storage.

  16. Some resistance mechanisms to ultraviolet radiation

    International Nuclear Information System (INIS)

    Alcantara D, D.

    2002-12-01

    The cyclical exposure of bacterial cells to the ultraviolet light (UV) it has as consequence an increment in the resistance to the lethal effects of this type of radiation, increment that happens as a result of a selection process of favorable genetic mutations induced by the same UV light. With object to study the reproducibility of the genetic changes and the associate mechanisms to the resistance to UV in the bacteria Escherichia coli, was irradiated cyclically with UV light five different derived cultures of a single clone, being obtained five stumps with different resistance grades. The genetic mapping Hfr revealed that so much the mutation events like of selection that took place during the adaptation to the UV irradiation, happened of random manner, that is to say, each one of the resistant stumps it is the result of the unspecified selection of mutations arisen at random in different genes related with the repair and duplication of the DNA. (Author)

  17. Antibacterial Mechanisms of Polymyxin and Bacterial Resistance

    Directory of Open Access Journals (Sweden)

    Zhiliang Yu

    2015-01-01

    Full Text Available Multidrug resistance in pathogens is an increasingly significant threat for human health. Indeed, some strains are resistant to almost all currently available antibiotics, leaving very limited choices for antimicrobial clinical therapy. In many such cases, polymyxins are the last option available, although their use increases the risk of developing resistant strains. This review mainly aims to discuss advances in unraveling the mechanisms of antibacterial activity of polymyxins and bacterial tolerance together with the description of polymyxin structure, synthesis, and structural modification. These are expected to help researchers not only develop a series of new polymyxin derivatives necessary for future medical care, but also optimize the clinical use of polymyxins with minimal resistance development.

  18. A Multibacteriocin Cheese Starter System, Comprising Nisin and Lacticin 3147 in Lactococcus lactis, in Combination with Plantaricin from Lactobacillus plantarum.

    Science.gov (United States)

    Mills, S; Griffin, C; O'Connor, P M; Serrano, L M; Meijer, W C; Hill, C; Ross, R P

    2017-07-15

    Functional starter cultures demonstrating superior technological and food safety properties are advantageous to the food fermentation industry. We evaluated the efficacies of single- and double-bacteriocin-producing starters of Lactococcus lactis capable of producing the class I bacteriocins nisin A and/or lacticin 3147 in terms of starter performance. Single producers were generated by mobilizing the conjugative bacteriophage resistance plasmid pMRC01, carrying lacticin genetic determinants, or the conjugative transposon Tn 5276 , carrying nisin genetic determinants, to the commercial starter L. lactis CSK2775. The effect of bacteriocin coproduction was examined by superimposing pMRC01 into the newly constructed nisin transconjugant. Transconjugants were improved with regard to antimicrobial activity and bacteriophage insensitivity compared to the recipient strain, and the double producer was immune to both bacteriocins. Bacteriocin production in the starter was stable, although the recipient strain proved to be a more efficient acidifier than transconjugant derivatives. Overall, combinations of class I bacteriocins (the double producer or a combination of single producers) proved to be as effective as individual bacteriocins for controlling Listeria innocua growth in laboratory-scale cheeses. However, using the double producer in combination with the class II bacteriocin producer Lactobacillus plantarum or using the lacticin producer with the class II producer proved to be most effective for reducing bacterial load. As emergence of bacteriocin tolerance was reduced 10-fold in the presence of nisin and lacticin, we suggest that the double producer in conjunction with the class II producer could serve as a protective culture providing a food-grade, multihurdle approach to control pathogenic growth in a variety of industrial applications. IMPORTANCE We generated a suite of single- and double-bacteriocin-producing starter cultures capable of generating the class I

  19. Dominant mechanisms of primary resistance differ from dominant mechanisms of secondary resistance to targeted therapies.

    Science.gov (United States)

    Asić, Ksenija

    2016-01-01

    The effectiveness of targeted therapies is currently limited, as almost all patients eventually acquire resistance within year/year and a half from therapy initiation and a small subset of a patients fail to respond at all, demonstrating intrinsic resistance. The aim of this review was to determine the potential common features and differences between the mechanisms of intrinsic and acquired resistance to targeted therapies by analyzing established resistance-generating alterations for ten FDA-approved targeted drugs. The frequency of alterations underlying intrinsic and acquired resistance shows distinctive pattern, where dominant mechanisms of intrinsic resistance include aberrations of signals downstream or upstream of the targeted protein and dominant mechanisms of acquired resistance refer to lesions in the target itself or alterations of signals at target-level that can mimic or compensate for target function. It appears that during the evolution of acquired resistance, the tumor cell is inclined to preserve the same oncogene addiction on a targeted protein it had prior to drug administration. On the other hand, intrinsic resistance develops early in tumorogenesis and is based on randomly selected mutated signals between targeted and non-targeted signaling pathways, leading to the acquisition of cancer hallmarks. In general, there is an overlap between the mechanisms of intrinsic and acquired resistance, but the occurrence frequency and distribution of alterations underlying intrinsic and acquired resistance to targeted therapies are significantly different. Focus should be placed on different group of genes in pursuing predictive markers for intrinsic and acquired resistance to targeted therapies. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  20. Glioblastoma Multiforme Therapy and Mechanisms of Resistance

    Directory of Open Access Journals (Sweden)

    Yulian P. Ramirez

    2013-11-01

    Full Text Available Glioblastoma multiforme (GBM is a grade IV brain tumor characterized by a heterogeneous population of cells that are highly infiltrative, angiogenic and resistant to chemotherapy. The current standard of care, comprised of surgical resection followed by radiation and the chemotherapeutic agent temozolomide, only provides patients with a 12–14 month survival period post-diagnosis. Long-term survival for GBM patients remains uncommon as cells with intrinsic or acquired resistance to treatment repopulate the tumor. In this review we will describe the mechanisms of resistance, and how they may be overcome to improve the survival of GBM patients by implementing novel chemotherapy drugs, new drug combinations and new approaches relating to DNA damage, angiogenesis and autophagy.

  1. Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy

    National Research Council Canada - National Science Library

    Huang, Chung-Yung

    2006-01-01

    .... Further, current clinical, pathological and molecular markers poorly predict the response and resistance of chemotherapy, and the molecular mechanisms of chemotherapy resistance are largely unknown...

  2. Targeting Mechanisms of Resistance to Taxane-Based Chemotherapy

    National Research Council Canada - National Science Library

    Huang, Chung-Ying

    2007-01-01

    .... Further current clinical pathological and molecular markers poorly predict the response and resistance of chemotherapy and the molecular mechanisms of chemotherapy resistance are largely unknown...

  3. [Molecular Mechanisms of Insulin Resistance: An Update].

    Science.gov (United States)

    Gutiérrez-Rodelo, Citlaly; Roura-Guiberna, Adriana; Olivares-Reyes, Jesús Alberto

    The biological actions of insulin are initiated by activating its membrane receptor, which triggers multiple signaling pathways to mediate their biological actions. Due to the importance of metabolic regulation and promoting functions of cell growth and proliferation, insulin actions are highly regulated to promote proper metabolic functioning and energy balance. If these mechanisms are altered, this can lead to a condition known as insulin resistance, which is the consequence of a deficient insulin signaling caused by mutations or post-translational modifications of the receptor or effector molecules located downstream. Insulin resistance is one of the main characteristics of pathological manifestations associated with type 2 diabetes mellitus, one of the leading causes of death in Mexico and worldwide. In recent years, it has been found that conditions such as inflammation, endoplasmic reticulum stress, and mitochondrial dysfunction promote insulin resistance. The aim of this review is to elucidate the molecular aspects of insulin resistance and the mechanisms involved in regulating its effects, with particular emphasis on the role of inflammation, endoplasmic reticulum stress, and mitochondrial dysfunction.

  4. Inhibition of Listeria monocytogenes on cold-smoked salmon by nisin and carbon dioxide atmosphere

    DEFF Research Database (Denmark)

    Nilsson, Lilian; Huss, Hans Henrik; Gram, Lone

    1997-01-01

    The bacteriostatic and bacteriocidal effect of nisin in combination with carbon dioxide, NaCl and low temperature on the survival of Listeria monocytogenes was investigated in in vitro model studies and in trials with cold-smoked salmon. Addition of nisin caused various degrees of inhibition....../ml. The most pronounced effect of nisin was found when 10(2) cfu/ml was grown in media with 5.0% NaCl and incubated in CO2 atmosphere (MBC = 30 IU/ml). The bactericidal effect of nisin was reduced in air and vacuum, and did not increase systematically with increasing NaCl concentrations. In general, nisin...

  5. EFFECTIVE FACTORS AND MODEL SYSTEMS IN THE INDUSTRIAL PRODUCTION OF NISIN

    Directory of Open Access Journals (Sweden)

    Ömer ŞİMŞEK

    2007-01-01

    Full Text Available Nisin is the first bacteriocin identified in Lactococcus lactis and belongs to type 1 lanthibiotic group. High nisin production in cultured media is related with the composition of fermentation medium, pH, produced nisin concentration and most importantly growth amount of cell. For industrial purpose, batch, fed-batch and continue fermentation systems were developed by regarding these factors. Maintaining efficient production of nisin having important potential at preservation of foods is important for both industrial production and using as starter culture. In this review the fermentation factors at nisin production were outlined and constructed model systems were compared.

  6. Incorporation of tryptophan analogues into the lantibiotic nisin.

    Science.gov (United States)

    Zhou, Liang; Shao, Jinfeng; Li, Qian; van Heel, Auke J; de Vries, Marcel P; Broos, Jaap; Kuipers, Oscar P

    2016-05-01

    Lantibiotics are posttranslationally modified peptides with efficient inhibitory activity against various Gram-positive bacteria. In addition to the original modifications, incorporation of non-canonical amino acids can render new properties and functions to lantibiotics. Nisin is the most studied lantibiotic and contains no tryptophan residues. In this study, a system was constructed to incorporate tryptophan analogues into nisin, which included the modification machinery (NisBTC) and the overexpression of tryptophanyl-tRNA synthetase (TrpRS). Tryptophan and three different tryptophan analogues (5-fluoroTrp (5FW), 5-hydroxyTrp (5HW) and 5-methylTrp (5MeW)) were successfully incorporated at four different positions of nisin (I1W, I4W, M17W and V32W). The incorporation efficiency of tryptophan analogues into mutants I1W, M17W and V32W was over 97 %, while the mutant I4W showed relatively low incorporation efficiency (69-93 %). The variants with 5FW showed relatively higher production yield, while 5MeW-containing variants showed the lowest yield. The dehydration efficiency of serines or threonines was affected by the tryptophan mutants of I4W and V32W. The affinity of the peptides for the cation-ion exchange and reverse phase chromatography columns was significantly reduced when 5HW was incorporated. The antimicrobial activity of IIW and its 5FW analogue both decreased two times compared to that of nisin, while that of its 5HW analogue decreased four times. The 5FW analogue of I4W also showed two times decreased activity than nisin. However, the mutant M17W and its 5HW analogue both showed 32 times reduced activity relative to that of nisin.

  7. Supporting data for comparative proteomic analysis of Listeria monocytogenes ATCC 7644 exposed to a sublethal concentration of nisin

    Directory of Open Access Journals (Sweden)

    Kendi Nishino Miyamoto

    2015-06-01

    Full Text Available Here we provide the LC–MS/MS data from a comparative analysis of Listeria monocytogenes ATCC 7644 treated and non-treated with a sublethal concentration of nisin (10−3 mg/mL. Protein samples were analyzed by multidimensional protein identification technology (MudPIT approach, in an off-line configuration. The raw MS/MS data allowed the detection of 49,591 spectra which resulted in 576 protein identifications. After Scaffold validation, 179 proteins were identified with high confidence. A label-free quantitative analysis based of normalized spectral abundance factor (NSAF was used and 13 proteins were found differentially expressed between nisin-treated and non-treated cells. Gene ontology analysis of differentially expressed proteins revealed that most of them are correlated to metabolic process, oxidative stress response mechanisms and molecular binding. A detailed analysis and discussion of these data may be found in Miyamoto et al. [1].

  8. Heterologous Expression of the Lactococcus lactis Bacteriocin, Nisin, in a Dairy Enterococcus Strain

    Science.gov (United States)

    Li, Haiping; O'Sullivan, Daniel J.

    2002-01-01

    The bacteriocin nisin is produced only by some strains of Lactococcus lactis, and to date production in other lactic acid bacteria has not been achieved. Enterococcus sp. strain N12β is a nisin-immune transconjugant obtained from a nisin-producing donor (L. lactis ATCC 11454) and a dairy recipient (Enterococcus sp. strain S12β), but it does not produce nisin. In this study, using PCR amplification, we confirmed that the whole nisin operon is likely present in Enterococcus sp. strain N12β. Northern hybridization of total RNA from strain N12β with a nisA probe and the results of reverse transcriptase PCR showed the lack of nisA transcription in this strain. However, nisA transcription was partially restored in strain N12β upon growth in the presence of exogenous nisin, and the nisA transcription signal was intensified after an increase in the external nisin level. Furthermore, bioassays showed that active nisin was produced in a dose-dependent fashion by strain N12β following induction by exogenous nisin. These results indicated that expression of the nisin genes in Enterococcus sp. strain N12β depended on autoinduction via signal transduction. However, the amount of external inducing signal required was significantly greater than the amount needed for autoinduction in L. lactis. PMID:12089020

  9. Effect of non-nutritional factors on nisin production

    African Journals Online (AJOL)

    USER

    2010-03-01

    Mar 1, 2010 ... positive bacteria, including pathogenic and food spoilage microorganisms such as clostridia, bacilli, Staphylococcus aureus, micrococci, lactobacilli and Listeria monocyto- genes. Nisin is used in over 48 countries, has ... may begin by measuring product yield as a response to nutritional (carbon, nitrogen ...

  10. Processing of byproducts to improve nisin production by ...

    African Journals Online (AJOL)

    One of them is its utilization as culture media, aiming to produce biomolecules with noble applications. Nisin is an extracellular peptide, produced by Lactococcus lactis, this peptide has been applied as a natural additive once it presents broad antibacterial activity. Applications of this bacteriocin include dental care products, ...

  11. Cloning of nis gene and Nisin purification from Lactococcus lactis ...

    African Journals Online (AJOL)

    user

    2014-12-31

    Dec 31, 2014 ... 1Department of Radiation Microbiology, National Center for Radiation Research and Technology (NCCRT), Cairo,. Egypt. 2Chemistry of Natural and ... other natural antibacterials, such as certain essential oils. Though it is considered a ... antimicrobial activity of nisin depending on the target microorganism.

  12. Optimization of fermentation medium for nisin production from ...

    African Journals Online (AJOL)

    Sequentially, Box-Behnken design experiments were implemented for further optimization. RSM combined with ANNGA were used for analysis of data. Specially, a RSM model was used for determining the individual effect and mutual interaction effect of tested variables on nisin titer (NT), an ANN model was used for NT ...

  13. Analysis and modeling of resistive switching mechanisms oriented to resistive random-access memory

    International Nuclear Information System (INIS)

    Huang Da; Wu Jun-Jie; Tang Yu-Hua

    2013-01-01

    With the progress of the semiconductor industry, the resistive random-access memory (RAM) has drawn increasing attention. The discovery of the memristor has brought much attention to this study. Research has focused on the resistive switching characteristics of different materials and the analysis of resistive switching mechanisms. We discuss the resistive switching mechanisms of different materials in this paper and analyze the differences of those mechanisms from the view point of circuitry to establish their respective circuit models. Finally, simulations are presented. We give the prospect of using different materials in resistive RAM on account of their resistive switching mechanisms, which are applied to explain their resistive switchings

  14. The novel sRNA s015 improves nisin yield by increasing acid tolerance of Lactococcus lactis F44.

    Science.gov (United States)

    Qi, Jiakun; Caiyin, Qinggele; Wu, Hao; Tian, Kairen; Wang, Binbin; Li, Yanni; Qiao, Jianjun

    2017-08-01

    Nisin, a polycyclic antibacterial peptide produced by Lactococcus lactis, is stable at low pH. Improving the acid tolerance of L. lactis could thus enhance nisin yield. Small non-coding RNAs (sRNAs) play essential roles in acid tolerance by regulating their target mRNAs at the post-transcriptional level. In this study, a novel sRNA, s015, was identified in L. lactis F44 via the use of RNA sequencing, qRT-PCR analysis, and Northern blotting. s015 improved the acid tolerance of L. lactis and boosted nisin yield at low pH. In silico predictions enabled us to construct a library of possible s015 target mRNAs. Statistical analysis and validation suggested that s015 contains a highly conserved region (5'-GAAAAAAAC-3') that likely encompasses the regulatory core of the sRNA. atpG, busAB, cysD, ilvB, tcsR, ung, yudD, and ywdA were verified as direct targets of s015, and the interactions between s015 and its target genes were elucidated. This work provided new insight into the adaptation mechanism of L. lactis under acid stress.

  15. Antimicrobial Peptide Resistance Mechanisms of Gram-Positive Bacteria.

    Science.gov (United States)

    Nawrocki, Kathryn L; Crispell, Emily K; McBride, Shonna M

    2014-10-13

    Antimicrobial peptides, or AMPs, play a significant role in many environments as a tool to remove competing organisms. In response, many bacteria have evolved mechanisms to resist these peptides and prevent AMP-mediated killing. The development of AMP resistance mechanisms is driven by direct competition between bacterial species, as well as host and pathogen interactions. Akin to the number of different AMPs found in nature, resistance mechanisms that have evolved are just as varied and may confer broad-range resistance or specific resistance to AMPs. Specific mechanisms of AMP resistance prevent AMP-mediated killing against a single type of AMP, while broad resistance mechanisms often lead to a global change in the bacterial cell surface and protect the bacterium from a large group of AMPs that have similar characteristics. AMP resistance mechanisms can be found in many species of bacteria and can provide a competitive edge against other bacterial species or a host immune response. Gram-positive bacteria are one of the largest AMP producing groups, but characterization of Gram-positive AMP resistance mechanisms lags behind that of Gram-negative species. In this review we present a summary of the AMP resistance mechanisms that have been identified and characterized in Gram-positive bacteria. Understanding the mechanisms of AMP resistance in Gram-positive species can provide guidelines in developing and applying AMPs as therapeutics, and offer insight into the role of resistance in bacterial pathogenesis.

  16. Effects of gene disruptions in the nisin gene cluster of Lactococcus lactis on nisin production and producer immunity

    NARCIS (Netherlands)

    Ra, Runar; Beerthuyzen, Marke M.; Vos, Willem M. de; Saris, Per E.J.; Kuipers, Oscar P.

    1999-01-01

    The lantibiotic nisin is produced by several strains of Lactococcus lactis subsp. lactis. The chromosomally located gene cluster nisABTCIPRKFEG is required for biosynthesis, development of immunity, and regulation of gene expression. In-frame deletions in the nisB and nisT genes, and disruption of

  17. Anti-listeria effects of chitosan-coated nisin-silica liposome on Cheddar cheese.

    Science.gov (United States)

    Cui, H Y; Wu, J; Li, C Z; Lin, L

    2016-11-01

    Listeria monocytogenes poses an increasing challenge to cheese production. To minimize the risk of bacterial contamination, a chitosan-coated nisin-silica liposome was engineered for the present study. We investigated the characteristics of nisin-silica liposomes and the anti-listeria effects of a chitosan-coated nisin-silica liposome on Cheddar cheese. The encapsulation efficiency of nisin in a liposome was sharply increased after it was adsorbed on a silica particle surface. Chitosan-coated nisin-silica liposomes displayed sustained antibacterial activity against L. monocytogenes, without affecting the sensory properties of the cheese. Chitosan-coated nisin-silica liposomes could be a promising active antimicrobial for cheese preservation. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  18. Functional properties of nisin-carbohydrate conjugates formed by radiation induced Maillard reaction

    Science.gov (United States)

    Muppalla, Shobita R.; Sonavale, Rahul; Chawla, Surinder P.; Sharma, Arun

    2012-12-01

    Nisin-carbohydrate conjugates were prepared by irradiating nisin either with glucose or dextran. Increase in browning and formation of intermediate products was observed with a concomitant decrease in free amino and reducing sugar groups indicating occurrence of the Maillard reaction catalyzed by irradiation. Nisin-carbohydrate conjugates showed a broad spectrum antibacterial activity against Gram negative bacteria (Escherichia coli, Pseudomonas fluorescence) as well as Gram positive bacteria (Staphylococcus aureus, Bacillus cereus). Results of antioxidant assays, including that of DPPH radical-scavenging activity and reducing power, showed that the nisin-dextran conjugates possessed better antioxidant potential than nisin-glucose conjugate. These results suggested that it was possible to enhance the functional properties of nisin by preparing radiation induced conjugates suitable for application in food industry.

  19. Determining the effects of green chemistry synthesized Ag-nisin nanoparticle on macrophage cells.

    Science.gov (United States)

    Moein, Masood; Imani Fooladi, Abbas Ali; Mahmoodzadeh Hosseini, Hamideh

    2018-01-01

    Bacteriocins are low molecular weight substances produced through post transcriptional changes. These molecules are easily degraded in mammalian gut by proteolytic enzymes especially protease. Nisin is a peptide with 34 aa and its structure contains a pentacyclic lanthionine and 4 beta metyllanthionine residues. Different formulations have been designed for nisin. Since "green synthesis" is a progressive method to prepare anti-microbial and anti-cancer compounds, this study aimed at green synthesis of nisin metal compounds to be used lower concentration still exerting nisin effects. For this purpose, a 1 mg/ml nisin solution was added to a 1 mM silver nitrate solution and incubated to synthesis nano Ag-nisin, then the optical density of new solution was detected using UV spectroscopy. To determine biomolecules in the Ag-nisin solution, the FTIR method was employed. The size and morphology of Ag-nisin was measured by TEM. The toxicity, inflammatory cytokines production, and intracellular ROS quantity was evaluated using MTT, ELISA and flow-cytometry. XRD pattern indicated the silver crystals in Ag-nisin solution. In addition, FTRI findings showed that the carbonyl groups of amino acid are potently able to bind to metal nanoparticles, cover, and prevent them from particle agglomeration. Treating macrophage cells with 10, 25, 50 and 100 μg/ml of Ag-nisin had no significant effect on the cell viability and intracellular ROS quantity compared to the control group. In addition, different concentrations of Ag-nisin had no effect on the IL-10 and TNF-α levels but caused an increased level of IL-12 in comparison with the control group. In the current study, for the first time, green synthesize was used to prepare Ag-nisin particles. The synthesized nanoparticle is able to induce inflammatory activity via increasing IL-12 without any change in the TNF-α level in macrophage cells. Copyright © 2017. Published by Elsevier Ltd.

  20. Antimicrobial Nisin Acts Against Saliva Derived Multi-Species Biofilms without Cytotoxicity to Human Oral Cells

    Directory of Open Access Journals (Sweden)

    Yvonne Lorraine Kapila

    2015-06-01

    Full Text Available Objectives: Nisin is a lantibiotic widely used for the preservation of food and beverages. Recently, investigators have reported that nisin may have clinical applications for treating bacterial infections. The aim of this study was to investigate the effects of ultra pure food grade Nisin ZP (> 95% purity on taxonomically diverse bacteria common to the human oral cavity and saliva derived multi-species oral biofilms, and to discern the toxicity of nisin against human cells relevant to the oral cavity. Methods: The MICs and MBCs of taxonomically distinct oral bacteria were determined using agar and broth dilution methods. To assess the effects of nisin on biofilms, two model systems were utilized: a static and a controlled flow microfluidic system. Biofilms were inoculated with pooled human saliva and fed filter-sterilized saliva for 20-22 h at 37°C. Nisin effects on cellular apoptosis and proliferation were evaluated using acridine orange/ethidium bromide fluorescent nuclear staining and lactate dehydrogenase activity assays. Results: Nisin inhibited planktonic growth of oral bacteria at low concentrations (2.5 – 50 μg/ml. Nisin also retarded development of multi-species biofilms at concentrations ≥ 1 μg/ml. Specifically, under biofilm model conditions, nisin interfered with biofilm development and reduced biofilm biomass and thickness in a dose-dependent manner. The treatment of pre-formed biofilms with nisin resulted in dose- and time-dependent disruption of the biofilm architecture along with decreased bacterial viability. Human cells relevant to the oral cavity were unaffected by the treatment of nisin at anti-biofilm concentrations and showed no signs of apoptotic changes unless treated with much higher concentrations (> 200 μg/ml. Conclusions: This work highlights the potential therapeutic value of high purity food grade nisin to inhibit the growth of oral bacteria and the development of biofilms relevant to oral diseases.

  1. Antimicrobial Effect of Nisin against Bacillus cereus in Beef Jerky during Storage

    OpenAIRE

    Lee, Na-Kyoung; Kim, Hyoun Wook; Lee, Joo Yeon; Ahn, Dong Uk; Kim, Cheon-Jei; Paik, Hyun-Dong

    2015-01-01

    The microbial distribution of raw materials and beef jerky, and the effect of nisin on the growth of Bacillus cereus inoculated in beef jerky during storage, were studied. Five strains of pathogenic B. cereus were detected in beef jerky, and identified with 99.8% agreement using API CHB 50 kit. To evaluate the effect of nisin, beef jerky was inoculated with approximately 3 Log CFU/g of B. cereus mixed culture and nisin (100 IU/g and 500 IU/g). During the storage of beef jerky without nisin, t...

  2. Molecular Mechanisms of Insulin Resistance Development

    Directory of Open Access Journals (Sweden)

    Vsevolod Arsen'evich Tkachuk

    2014-05-01

    Full Text Available Insulin resistance (IR is a phenomenon associated with an impaired ability of insulin to stimulate glucose uptake by target cells and to reduce the blood glucose level. A response increase in insulin secretion by the pancreas and hyperinsulinemia are compensatory reactions of the body. The development of IR leads to the inability of target cells to respond to insulin that results in developing type 2 diabetes mellitus (T2DM and metabolic syndrome. For this reason, the metabolic syndrome is defined in practice as a combination of IR with one or more pathologies such as T2DM, arterial hypertension, dyslipidemia, abdominal obesity, non-alcoholic fatty liver disease, and some others. However, a combination of high blood glucose and insulin levels always serves as its physiological criterion.IR should be considered as a systemic failure of the endocrine regulation in the body. Physiological causes of IR are diverse. The main ones are nutritional overload and accumulation of certain lipids and their metabolites in cells, low physical activity, chronic inflammation and stress of various nature, including oxidative and endoplasmic reticulum stress (impairment of damaged protein degradation in the cell. Recent studies have demonstrated that these physiological mechanisms likely act through a single intracellular scenario. This is the impairment of signal transduction from the insulin receptor to its targets via the negative feedback mechanism in intracellular insulin-dependent signaling cascades.This review describes the physiological and intracellular mechanisms of insulin action and focuses on their abnormalities upon IR development. Finally, feasible trends in early molecular diagnosis and therapy of IR are discussed.

  3. Resistance mechanisms to plant viruses: an overview

    NARCIS (Netherlands)

    Goldbach, R.W.; Bucher, E.C.; Prins, A.H.

    2003-01-01

    To obtain virus-resistant host plants, a range of operational strategies can be followed nowadays. While for decades plant breeders have been able to introduce natural resistance genes in susceptible genotypes without knowing precisely what these resistance traits were, currently a growing number of

  4. The Effect of Nisin and Clove Essential Oil on Shelf Life of Beef

    OpenAIRE

    KOPLAY, Zeliha; SEZER, Çiğdem

    2013-01-01

     In  this  study,  the  effects  of  nisin  and  clove  essential  oil  on  shelf  life  of  beef  were  investigated  in  order  to  evaluate  their   antimicrobial   activities.   It   was   determined   that   clove   essential   oil   has   a   wide   spectrum   on   Gram   (+)   and   Gram   (-­‐)  bacteria.   While   L.   monocytogenes   was   the   most   resistant   bacteria   among   the   Gram   (+)   bacteria,   B.   thermosphacta   was  found  to  be  the  most  sensitive  bacteri...

  5. Action and resistance mechanisms of antibiotics: A guide for clinicians

    Directory of Open Access Journals (Sweden)

    Garima Kapoor

    2017-01-01

    Full Text Available Infections account for a major cause of death throughout the developing world. This is mainly due to the emergence of newer infectious agents and more specifically due to the appearance of antimicrobial resistance. With time, the bacteria have become smarter and along with it, massive imprudent usage of antibiotics in clinical practice has resulted in resistance of bacteria to antimicrobial agents. The antimicrobial resistance is recognized as a major problem in the treatment of microbial infections. The biochemical resistance mechanisms used by bacteria include the following: antibiotic inactivation, target modification, altered permeability, and “bypass” of metabolic pathway. Determination of bacterial resistance to antibiotics of all classes (phenotypes and mutations that are responsible for bacterial resistance to antibiotics (genetic analysis are helpful. Better understanding of the mechanisms of antibiotic resistance will help clinicians regarding usage of antibiotics in different situations. This review discusses the mechanism of action and resistance development in commonly used antimicrobials.

  6. Efficacies of nisin A and nisin V semipurified preparations alone and in combination with plant essential oils for controlling Listeria monocytogenes.

    Science.gov (United States)

    Field, Des; Daly, Karen; O'Connor, Paula M; Cotter, Paul D; Hill, Colin; Ross, R Paul

    2015-04-01

    The food-borne pathogenic bacterium Listeria is known for relatively low morbidity and high mortality rates, reaching up to 25 to 30%. Listeria is a hardy organism, and its control in foods represents a significant challenge. Many naturally occurring compounds, including the bacteriocin nisin and a number of plant essential oils, have been widely studied and are reported to be effective as antimicrobial agents against spoilage and pathogenic microorganisms. The aim of this study was to investigate the ability of semipurified preparations (SPP) containing either nisin A or an enhanced bioengineered derivative, nisin V, alone and in combination with low concentrations of the essential oils thymol, carvacrol, and trans-cinnamaldehyde, to control Listeria monocytogenes in both laboratory media and model food systems. Combinations of nisin V-containing SPP (25 μg/ml) with thymol (0.02%), carvacrol (0.02%), or cinnamaldehyde (0.02%) produced a significantly longer lag phase than any of the essential oil-nisin A combinations. In addition, the log reduction in cell counts achieved by the nisin V-carvacrol or nisin V-cinnamaldehyde combinations was twice that of the equivalent nisin A-essential oil treatment. Significantly, this enhanced activity was validated in model food systems against L. monocytogenes strains of food origin. We conclude that the fermentate form of nisin V in combination with carvacrol and cinnamaldehyde offers significant advantages as a novel, natural, and effective means to enhance food safety by inhibiting food-borne pathogens such as L. monocytogenes. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  7. Protective effects of soybean protein and egg white protein on the antibacterial activity of nisin in the presence of trypsin.

    Science.gov (United States)

    Pan, Dan; Zhang, Dong; Hao, Limin; Lin, Songyang; Kang, Qiaozhen; Liu, Xin; Lu, Laizheng; Lu, Jike

    2018-01-15

    The using of nisin to prevent foodborne pathogens (Staphylococcus aureus and Listeria monocytogenes) from contamination has received broad attentions during meat processing. However, the application of nisin has been limited because its antibacterial activity may be inhibited by trypsin. In this study, the protective effects of soybean protein and egg white protein on antibacterial activity of nisin were evaluated. It could be concluded that exogenous trypsin decreased the antibacterial activity of nisin, soybean protein and egg white protein could keep the nisin activity from enzymolysis of trypsin. Trypsin inhibitors in soybean protein and egg white protein could protect the antibacterial activity of nisin. Nisin with soybean protein or egg white protein in cooked meat product presented better quality preservation effects than nisin alone in the presence of trypsin. The total viable counts (TVC) and total volatile basic nitrogen (TVB-N) of nisin-treated group were significantly higher than these in nisin-soybean protein-treated and nisin-egg white protein-treated groups with trypsin. This study showed the potential of using soybean protein and egg white protein to stabilize the antibacterial activity of nisin under high trypsin conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Mechanisms and circumvention of cellular resistance to cisplatin.

    NARCIS (Netherlands)

    Hospers, Geesiena Alberdina Petronella

    1989-01-01

    Cisplatin (CDDP) is an active cytostatic agent. A limitation to its effectiveness initially or appearing during cystatic treatment is the occurrence of resistance. This thesis describes mechanisms wich are responsible for acquired cellular CDDP resistance. To investigate cellular CDDP resistance, a

  9. Mechanisms of rhizobacteria-mediated induced systemic resistance

    NARCIS (Netherlands)

    Hase, S.; Pieterse, C.M.J.; Loon, L.C. van

    2001-01-01

    Some of non-pathogenic rhizosphere bacteria reduce disease by activating a resistance mechanism in the plant called rhizobacteria-mediated induced systemic resistance (ISR). Rhizobacteria-mediated ISR resembles classic pathogen-induced systemic acquired resistance (SAR) in that both types of

  10. Shigella Antimicrobial Drug Resistance Mechanisms, 2004-2014.

    Science.gov (United States)

    Nüesch-Inderbinen, Magdalena; Heini, Nicole; Zurfluh, Katrin; Althaus, Denise; Hächler, Herbert; Stephan, Roger

    2016-06-01

    To determine antimicrobial drug resistance mechanisms of Shigella spp., we analyzed 344 isolates collected in Switzerland during 2004-2014. Overall, 78.5% of isolates were multidrug resistant; 10.5% were ciprofloxacin resistant; and 2% harbored mph(A), a plasmid-mediated gene that confers reduced susceptibility to azithromycin, a last-resort antimicrobial agent for shigellosis.

  11. Antibiotic resistance trends and mechanisms in the foodborne pathogen, Campylobacter.

    Science.gov (United States)

    Tang, Yizhi; Fang, Liangxing; Xu, Changyun; Zhang, Qijing

    2017-11-23

    Campylobacter is a major foodborne pathogen and is commonly present in food producing animals. This pathogenic organism is highly adaptable and has become increasingly resistant to various antibiotics. Recently, both the Centers for Disease Control and Prevention and the World Health Organization have designated antibiotic-resistant Campylobacter as a serious threat to public health. For the past decade, multiple mechanisms conferring resistance to clinically important antibiotics have been described in Campylobacter, and new resistance mechanisms constantly emerge in the pathogen. Some of the recent examples include the erm(B) gene conferring macrolide resistance, the cfr(C) genes mediating resistance to florfenicol and other antimicrobials, and a functionally enhanced variant of the multidrug resistance efflux pump, CmeABC. The continued emergence of new resistance mechanisms illustrates the extraordinary adaptability of Campylobacter to antibiotic selection pressure and demonstrate the need for innovative strategies to control antibiotic-resistant Campylobacter. In this review, we will briefly summarize the trends of antibiotic resistance in Campylobacter and discuss the mechanisms of resistance to antibiotics used for animal production and important for clinical therapy in humans. A special emphasis will be given to the newly discovered antibiotic resistance.

  12. Mechanisms of Antimicrobial Peptide Resistance in Gram-Negative Bacteria

    Directory of Open Access Journals (Sweden)

    Victor I. Band

    2014-12-01

    Full Text Available Cationic antimicrobial peptides (CAMPs are important innate immune defenses that inhibit colonization by pathogens and contribute to clearance of infections. Gram-negative bacterial pathogens are a major target, yet many of them have evolved mechanisms to resist these antimicrobials. These resistance mechanisms can be critical contributors to bacterial virulence and are often crucial for survival within the host. Here, we summarize methods used by Gram-negative bacteria to resist CAMPs. Understanding these mechanisms may lead to new therapeutic strategies against pathogens with extensive CAMP resistance.

  13. A Comparative Study Between the Antibacterial Effect of Nisin and Nisin-Loaded Chitosan/Alginate Nanoparticles on the Growth of Staphylococcus aureus in Raw and Pasteurized Milk Samples.

    Science.gov (United States)

    Zohri, Maryam; Alavidjeh, Mohammad Shafiee; Haririan, Ismaeil; Ardestani, Mehdi Shafiee; Ebrahimi, Seyed Esmaeil Sadat; Sani, Hadi Tarighati; Sadjadi, Seyed Kazem

    2010-12-01

    The aim of this study was to evaluate the antibacterial effect of nisin-loaded chitosan/alginate nanoparticles as a novel antibacterial delivery vehicle. The nisin-loaded nanoparticles were prepared using colloidal dispersion of the chitosan/alginate polymers in the presence of nisin. After the preparation of the nisin-loaded nanoparticles, their physicochemical properties such as size, shape, and zeta potential of the formulations were studied using scanning electron microscope and nanosizer instruments, consecutively. FTIR and differential scanning calorimetery studies were performed to investigate polymer-polymer or polymer-protein interactions. Next, the release kinetics and entrapment efficiency of the nisin-loaded nanoparticles were examined to assess the application potential of these formulations as a candidate vector. For measuring the antibacterial activity of the nisin-loaded nanoparticles, agar diffusion and MIC methods were employed. The samples under investigation for total microbial counts were pasteurized and raw milks each of which contained the nisin-loaded nanoparticles and inoculated Staphylococcus aureus (ATCC 19117 at 10(6) CFU/mL), pasteurized and raw milks each included free nisin and S. aureus (10(6) CFU/mL), and pasteurized and raw milks each had S. aureus (10(6) CFU/mL) in as control. Total counts of S. aureus were measured after 24 and 48 h for the pasteurized milk samples and after the time intervals of 0, 6, 10, 14, 18, and 24 h for the raw milk samples, respectively. According to the results, entrapment efficiency of nisin inside of the nanoparticles was about 90-95%. The average size of the nanoparticles was 205 nm, and the average zeta potential of them was -47 mV. In agar diffusion assay, an antibacterial activity (inhibition zone diameter, at 450 IU/mL) about 2 times higher than that of free nisin was observed for the nisin-loaded nanoparticles. MIC of the nisin-loaded nanoparticles (0.5 mg/mL) was about four times less than

  14. Reduction of Clostridium sporogenes spore outgrowth in natural sausage casings using nisin.

    Science.gov (United States)

    Wijnker, J J; Weerts, E A W S; Breukink, E J; Houben, J H; Lipman, L J A

    2011-08-01

    Preservation of natural sausage casings using dry salt or saturated brine is regarded as sufficient to inactivate vegetative pathogenic non-spore-forming bacteria present on the casings. Although the outgrowth of bacterial spores is prevented by salt or saturated brine preservation, these spores will remain present and develop into vegetative cells when conditions are more favourable. To prevent subsequent outgrowth additional preservation measures should be implemented. In the experiments described the use of nisin was evaluated to reduce outgrowth of spores in desalinated casings. The bacteriocin nisin was chosen because of its known efficacy against spore-forming bacteria and their spores in various foodstuffs. Clostridium spore suspensions (Clostridium sporogenes, ATCC 3584) were used in two concentrations to inoculate three nisin concentrations (10, 50, 100 μg/mL) in water containing gamma-irradiated casings. Additionally, the binding of nisin to casings, using (14)C-labeled nisin Z and subsequent availability of nisin were evaluated. Results demonstrate that nisin is partly reversibly bound to casings and can reduce the outgrowth of Clostridium spores in the model used by approximately 1 log(10) (90%). However, the biological relevance of these results needs to be determined further by conducting industrial trials before any recommendation can be made on the practical implementation of nisin in the preservation of natural sausage casings. Copyright © 2011 Elsevier Ltd. All rights reserved.

  15. Nisin Migration in Shelf Stable, Tuna-Filled Tortillas During Storage

    Science.gov (United States)

    2014-09-22

    J., and Lipman L. 2011. Reduction of Clostridium sporogenes spore outgrowth in natural sausage casings using nisin. Food Microbiology Volume 28:974– 979. ...Kruijff, B. 1999. The lantibiotic nisin, a special case or not? BBA Biomembranes volume 1462:223-234 Carter, M., personal communication, 2012

  16. Effect of non-nutritional factors on nisin production | Tafreshi | African ...

    African Journals Online (AJOL)

    order to assess some of non-nutritional factors and how they influence the nisin production in batch cultivation, a laboratory scale study was performed. Lactococcus lactis subsp. lactis ATCC 11454 produced nisin and Micrococcus luteus ATCC 10240 was used in bioassay measurement as the nisinsensitive strain. The age ...

  17. Using complexation for the microencapsulation of nisin in biopolymer matrices by spray-drying.

    Science.gov (United States)

    Ben Amara, Chedia; Kim, Lanhee; Oulahal, Nadia; Degraeve, Pascal; Gharsallaoui, Adem

    2017-12-01

    The aim of this study is to investigate the potential of complexation to encapsulate nisin (5g/L concentration) using spray-drying technique and to evaluate how complexation with pectin or alginate (2g/L concentration) can preserve nisin structure and antimicrobial activity. Spray-drying of nisin-low methoxyl pectin or nisin-alginate electrostatic complexes has led to the microencapsulation of the peptide in different networks that were highly influenced by the polysaccharide type. Turbidity and particle size measurements indicated that while spray-drying promoted the aggregation of nisin-pectin complexes, it favored the dissociation of nisin-alginate aggregates to form individual complexes. Structural changes of nisin induced by complexation with pectin or alginate and spray-drying were studied by using UV-Vis absorption and fluorescence spectroscopy. The results showed that complexation with pectin or alginate preserved nisin structure as well as its antimicrobial activity during spray-drying. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Mechanisms of hepatitis B virus resistance development.

    Science.gov (United States)

    Warner, Nadia; Locarnini, Stephen

    2014-01-01

    Hepatitis B virus (HBV) resistance to nucleos(t)ide analogue (NA) therapy is essentially structure specific, with each NA falling within three main structural groups. Resistance to each of these is characterized by specific mutations in the reverse transcriptase domains of the HBV polymerase, and may be associated with compensatory mutations which can increase replication. HBV polymerase is considered to have a traditional 'right-handed' structural conformation, and each of the resistance mutations is predicted to cause a specific structural change of the polymerase, thereby preventing incorporation of NA into replicating DNA. The selection of resistance occurs at different rates for each NA, and is affected by the high mutational rate of HBV and the ability of the drug to suppress viral replication. Some mutations or combinations of mutations may be associated with multidrug resistance, limiting treatment options. In contrast to most other viruses, resistance in HBV is confounded by the overlapping surface gene, the major NA-resistant mutations also altering the surface proteins in most cases, potentially altering virus secretion and neutralization, which may pose a public health threat in the future. © 2014 S. Karger AG, Basel.

  19. Molecular mechanisms of bortezomib resistant adenocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Erika Suzuki

    Full Text Available Bortezomib (Velcade™ is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM. Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ~30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response.

  20. Mechanism for detecting NAPL using electrical resistivity imaging

    Science.gov (United States)

    Halihan, Todd; Sefa, Valina; Sale, Tom; Lyverse, Mark

    2017-10-01

    The detection of non-aqueous phase liquid (NAPL) related impacts in freshwater environments by electrical resistivity imaging (ERI) has been clearly demonstrated in field conditions, but the mechanism generating the resistive signature is poorly understood. An electrical barrier mechanism which allows for detecting NAPLs with ERI is tested by developing a theoretical basis for the mechanism, testing the mechanism in a two-dimensional sand tank with ERI, and performing forward modeling of the laboratory experiment. The NAPL barrier theory assumes at low bulk soil NAPL concentrations, thin saturated NAPL barriers can block pore throats and generate a detectable electrically resistive signal. The sand tank experiment utilized a photographic technique to quantify petroleum saturation, and to help determine whether ERI can detect and quantify NAPL across the water table. This experiment demonstrates electrical imaging methods can detect small quantities of NAPL of sufficient thickness in formations. The bulk volume of NAPL is not the controlling variable for the amount of resistivity signal generated. The resistivity signal is primarily due to a zone of high resistivity separate phase liquid blocking current flow through the fully NAPL saturated pores spaces. For the conditions in this tank experiment, NAPL thicknesses of 3.3 cm and higher in the formation was the threshold for detectable changes in resistivity of 3% and greater. The maximum change in resistivity due to the presence of NAPL was an increase of 37%. Forward resistivity models of the experiment confirm the barrier mechanism theory for the tank experiment.

  1. Mechanisms Linking Inflammation to Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Li Chen

    2015-01-01

    Full Text Available Obesity is now widespread around the world. Obesity-associated chronic low-grade inflammation is responsible for the decrease of insulin sensitivity, which makes obesity a major risk factor for insulin resistance and related diseases such as type 2 diabetes mellitus and metabolic syndromes. The state of low-grade inflammation is caused by overnutrition which leads to lipid accumulation in adipocytes. Obesity might increase the expression of some inflammatory cytokines and activate several signaling pathways, both of which are involved in the pathogenesis of insulin resistance by interfering with insulin signaling and action. It has been suggested that specific factors and signaling pathways are often correlated with each other; therefore, both of the fluctuation of cytokines and the status of relevant signaling pathways should be considered during studies analyzing inflammation-related insulin resistance. In this paper, we discuss how these factors and signaling pathways contribute to insulin resistance and the therapeutic promise targeting inflammation in insulin resistance based on the latest experimental studies.

  2. Molecular mechanisms of methicillin resistance in Staphylococcus aureus.

    Science.gov (United States)

    Domínguez, M A; Liñares, J; Martín, R

    1997-09-01

    Methicillin-resistant Staphylococcus aureus (MRSA) strains are among the most common nosocomial pathogens. The most significant mechanism of resistance to methicillin in this-species is the acquisition of a genetic determinant (mecA gene). However, resistance seems to have a more complex molecular basis, since additional chromosomal material is involved in such resistance. Besides, overproduction of penicillinase and/or alterations in the PBPs can contribute to the formation of resistance phenotypes. Genetic and environmental factors leading to MRSA are reviewed.

  3. Tumor cell heterogeneity: impact on mechanisms of therapeutic drug resistance

    International Nuclear Information System (INIS)

    Richardson, Mary E.; Siemann, Dietmar W.

    1997-01-01

    Purpose: The aim of these studies was to determine whether chemotherapy-resistant tumor cell sublines derived from a single starting cell population with identical treatment protocols, have the same mechanism of resistance. Methods and Materials: Twelve cyclophosphamide-resistant sublines were derived from KHT-iv murine sarcoma cells by repeated exposures to 2, 4, or 8 μg/ml doses of 4-hydroperoxycyclophosphamide (4-OOHCP). To investigate possible mechanisms of resistance, glutathione (GSH) levels, glutathione S-transferase (GST) activity, and aldehyde dehydrogenase (ALDH) activity were determined. In addition, studies with the GSH depletor buthionine sulfoximine (BSO) and the ALDH inhibitor diethylamino-benzaldehyde (DEAB) were undertaken. Results: Resistant factors to 4-OOHCP, assessed at 10% clonogenic cell survival, ranged from 1.5-7.0 for the various cell lines. Crossresistance to melphalan and adriamycin also were commonly observed. Increased GSH levels, GST activity and ALDH activity were detected in the sublines but not all exhibited the same pattern of biochemical alterations. The response to GSH and ALDH inhibitors also varied among the sublines; the resistance being reversible in some cell lines but not others. Conclusion: The present results indicate that when resistant sublines are derived simultaneously from the same starting cell population, the observed mechanisms of resistance may not be the same in each of the variants. These findings support the hypothesis that preexisting cellular heterogeneity may affect mechanisms of acquired resistance

  4. Mechanism of Resistance to Glyphosate in Lolium perenne from Argentina

    Directory of Open Access Journals (Sweden)

    Marcos Yanniccari

    2017-10-01

    Full Text Available In Argentina, glyphosate resistance was reported in a Lolium perenne population after 12 years of successful herbicide use. The aim of the current paper was to put in evidence for the mechanism of glyphosate resistance of this weed. Susceptible leaves treated with different doses of glyphosate and incubated in vitro showed an accumulation of shikimic acid of around three to five times the basal level, while no changes were detected in leaves of glyphosate-resistant plants. The resistance mechanism prevents shikimate accumulation in leaves, even under such tissue-isolation conditions. The activity of the glyphosate target enzyme (EPSPS: 5-enolpyruvylshikimate-3-phosphate synthase was quantified at different herbicide concentrations. EPSPS from resistant plants showed no difference in glyphosate-sensitivity compared to EPSPS from susceptible plants, and, accordingly, no amino acid substitution causing mutations associated with resistance were found. While the glyphosate target enzymes were equally sensitive, the basal EPSPS activity in glyphosate resistant plants was approximately 3-fold higher than the EPSPS activity in susceptible plants. This increased EPSPS activity in glyphosate resistant plants was associated with a 15-fold higher expression of EPSPS compared with susceptible plants. Therefore, the over-expression of EPSPS appears to be the main mechanism responsible for resistance to glyphosate. This mechanism has a constitutive character and has important effects on plant fitness, as recently reported.

  5. Resistance Mechanisms in an In Vitro-Selected Amoxicillin-Resistant Strain of Helicobacter pylori▿

    OpenAIRE

    Co, Edgie-Mark A.; Schiller, Neal L.

    2006-01-01

    We investigated the β-lactam resistance mechanism(s) of an in vitro-selected amoxicillin-resistant Helicobacter pylori strain (AmoxR). Our results demonstrated that resistance is due to a combination of amino acid substitutions in penicillin binding protein 1 (PBP1), HopB, and HopC identified in AmoxR, resulting in decreased affinity of PBP1 for amoxicillin and decreased accumulation of penicillin.

  6. Physiological mechanism of resistance to anthracnose of different ...

    African Journals Online (AJOL)

    However, enzyme activity of resistant cultivars improved markedly after pathogen inoculation, while those of susceptible cultivars did not change. This study broadens the understanding of the mechanisms of disease resistance in Camellia. Keywords: Anthracnose, Camellia oleifera, phenylalanine ammonia lyase, ...

  7. Nucleus geometry and mechanical properties of resistance spot ...

    Indian Academy of Sciences (India)

    Abstract. In this study, mechanical properties of resistance spot welding of DP450 and DP600, galvanized and ungalvanized automotive sheets have been investigated. The specimens have been joined by resistance spot welding at different weld currents and times. Welded specimens have been examined for their ...

  8. Mechanisms of drought resistance in grain: II Stomatal regulation ...

    African Journals Online (AJOL)

    Earlier research works conducted to identify mechanisms of drought resistance in grain legumes under soil water stress of -0.6 MPa showed that drought resistance (maintenace of turgor) in chick pea was due to a significant decrease in osmotic potential (osmotic adjustment) while in common bean it was due to ...

  9. Biomarkers and mechanisms of natural disease resistance in dairy cows

    NARCIS (Netherlands)

    Altena, van S.E.C.

    2016-01-01

    The aim of this thesis was to define and test biomarkers for disease resistance in dairy cows and to determine the underlying mechanism in natural disease resistance. The health status of the cows is an important issue in dairy farming. Due to the mandatory reduction in the use of antibiotics,

  10. Adaptive Mechanisms Underlying Microbial Resistance to Disinfectants

    Science.gov (United States)

    2016-02-01

    ammonium compounds RTU SDS-PAGE ready-to- use sodium dodecyl (lauryl) sulfate-polyacrylamide gel electrophoresis SNP single nucleotide polymorphism TSB...resistance to Lysol, an all-purpose cleaner and disinfectant (U.S. Environmental Protection Agency regulation no. 777-89 [ready-to- use (RTU) 1:16...dilution]). A clinical surrogate, Escherichia coli, was used in these studies. E. coli cells were grown in the absence or presence of Lysol. The parent

  11. Mechanisms Linking Inflammation to Insulin Resistance

    OpenAIRE

    Chen, Li; Chen, Rui; Wang, Hua; Liang, Fengxia

    2015-01-01

    Obesity is now widespread around the world. Obesity-associated chronic low-grade inflammation is responsible for the decrease of insulin sensitivity, which makes obesity a major risk factor for insulin resistance and related diseases such as type 2 diabetes mellitus and metabolic syndromes. The state of low-grade inflammation is caused by overnutrition which leads to lipid accumulation in adipocytes. Obesity might increase the expression of some inflammatory cytokines and activate several sig...

  12. Conduction Mechanism of Valence Change Resistive Switching Memory: A Survey

    Directory of Open Access Journals (Sweden)

    Ee Wah Lim

    2015-09-01

    Full Text Available Resistive switching effect in transition metal oxide (TMO based material is often associated with the valence change mechanism (VCM. Typical modeling of valence change resistive switching memory consists of three closely related phenomena, i.e., conductive filament (CF geometry evolution, conduction mechanism and temperature dynamic evolution. It is widely agreed that the electrochemical reduction-oxidation (redox process and oxygen vacancies migration plays an essential role in the CF forming and rupture process. However, the conduction mechanism of resistive switching memory varies considerably depending on the material used in the dielectric layer and selection of electrodes. Among the popular observations are the Poole-Frenkel emission, Schottky emission, space-charge-limited conduction (SCLC, trap-assisted tunneling (TAT and hopping conduction. In this article, we will conduct a survey on several published valence change resistive switching memories with a particular interest in the I-V characteristic and the corresponding conduction mechanism.

  13. Chemotherapy resistance mechanisms in advanced skin cancer

    Directory of Open Access Journals (Sweden)

    Bhuvanesh Sukhlal Kalal

    2017-03-01

    Full Text Available Melanoma is a most dangerous and deadly type of skin cancer, and considered intrinsically resistant to both radiotherapy and chemotherapy. It has become a major public health concern as the incidence of melanoma has been rising steadily over recent decades with a 5-year survival remaining less than 5%. Detection of the disease in early stage may be curable, but late stage metastatic disease that has spread to other organs has an extremely poor prognosis with a median survival of less than 10 months. Since metastatic melanoma is unresponsive to therapy that is currently available, research is now focused on different treatment strategies such as combinations of surgery, chemotherapy and radiotherapy. The molecular basis of resistance to chemotherapy seen in melanoma is multifactorial; defective drug transport system, altered apoptotic pathway, deregulation of apoptosis and/or changes in enzymatic systems that mediate cellular metabolic machinery. Understanding of alterations in molecular processes involved in drug resistance may help in developing new therapeutic approaches to treatment of malignant melanoma.

  14. Molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis clinical isolates

    Directory of Open Access Journals (Sweden)

    Meng Dong-Ya

    2014-01-01

    Full Text Available To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs of DNA gyrase (gyrA and gyrB and topoisomerase IV (parC and parE in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX, intermediate resistant to Levofloxacin (LVX and Sparfloxacin (SFX, and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.

  15. Molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis clinical isolates.

    Science.gov (United States)

    Meng, Dong-Ya; Sun, Chang-Jian; Yu, Jing-Bo; Ma, Jun; Xue, Wen-Cheng

    2014-01-01

    To evaluate the molecular mechanism of fluoroquinolones resistance in Mycoplasma hominis (MH) clinical strains isolated from urogenital specimens. 15 MH clinical isolates with different phenotypes of resistance to fluoroquinolones antibiotics were screened for mutations in the quinolone resistance-determining regions (QRDRs) of DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) in comparison with the reference strain PG21, which is susceptible to fluoroquinolones antibiotics. 15 MH isolates with three kinds of quinolone resistance phenotypes were obtained. Thirteen out of these quinolone-resistant isolates were found to carry nucleotide substitutions in either gyrA or parC. There were no alterations in gyrB and no mutations were found in the isolates with a phenotype of resistance to Ofloxacin (OFX), intermediate resistant to Levofloxacin (LVX) and Sparfloxacin (SFX), and those susceptible to all three tested antibiotics. The molecular mechanism of fluoroquinolone resistance in clinical isolates of MH was reported in this study. The single amino acid mutation in ParC of MH may relate to the resistance to OFX and LVX and the high-level resistance to fluoroquinolones for MH is likely associated with mutations in both DNA gyrase and the ParC subunit of topoisomerase IV.

  16. Dietary nisin modulates the gastrointestinal microbial ecology and enhances growth performance of the broiler chickens.

    Directory of Open Access Journals (Sweden)

    Damian Józefiak

    Full Text Available Due to antimicrobial properties, nisin is one of the most commonly used and investigated bacteriocins for food preservation. Surprisingly, nisin has had limited use in animal feed as well as there are only few reports on its influence on microbial ecology of the gastrointestinal tract (GIT. The present study therefore aimed at investigating effects of dietary nisin on broiler chicken GIT microbial ecology and performance in comparison to salinomycin, the widely used ionophore coccidiostat. In total, 720 one-day-old male Ross 308 chicks were randomly distributed to six experimental groups. The positive control (PC diet was supplemented with salinomycin (60 mg/kg. The nisin (NI diets were supplemented with increasing levels (100, 300, 900 and 2700 IU nisin/g, respectively of the bacteriocin. The negative control (NC diet contained no additives. At slaughter (35 days of age, activity of specific bacterial enzymes (α- and β-glucosidases, α-galactosidases and β-glucuronidase in crop, ileum and caeca were significantly higher (P<0.05 in the NC group, and nisin supplementation decreased the enzyme activities to levels observed for the PC group. A similar inhibitory influence on bacterial activity was reflected in the levels of short-chain fatty acids (SCFA and putrefactive SCFA (PSCFA in digesta from crop and ileum; no effect was observed in caeca. Counts of Bacteroides and Enterobacteriacae in ileum digesta were significantly (P<0.001 decreased by nisin and salinomycin, but no effects were observed on the counts of Clostridium perfringens, Lactobacillus/Enterococcus and total bacteria. Like salinomycin, nisin supplementation improved broiler growth performance in a dose-dependent manner; compared to the NC group, the body weight gain of the NI₉₀₀ and NI₂₇₀₀ groups was improved by 4.7 and 8.7%, respectively. Our findings suggest that dietary nisin exerts a mode of action similar to salinomycin and could be considered as a dietary

  17. Testing and Modeling of Mechanical Characteristics of Resistance Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels

    2003-01-01

    The dynamic mechanical response of resistance welding machine is very important to the weld quality in resistance welding especially in projection welding when collapse or deformation of work piece occurs. It is mainly governed by the mechanical parameters of machine. In this paper, a mathematical...... model for characterizing the dynamic mechanical responses of machine and a special test set-up called breaking test set-up are developed. Based on the model and the test results, the mechanical parameters of machine are determined, including the equivalent mass, damping coefficient, and stiffness...

  18. Inactivation of Listeria innocua in skim milk by pulsed electric fields and nisin.

    Science.gov (United States)

    Calderón-Miranda, M L; Barbosa-Cánovas, G V; Swanson, B G

    1999-10-01

    Pulsed electric fields (PEF) is an emerging nonthermal processing technology used to inactivate microorganisms in liquid foods such as milk. PEF results in loss of cell membrane functionality that leads to inactivation of the microorganism. There are many processes that aid in the stability and safety of foods. The combination of different preservation factors, such as nisin and PEF, to control microorganisms should be explored. The objective of this research was to study the inactivation of Listeria innocua suspended in skim milk by PEF as well as the sensitization of PEF treated L. innocua to nisin. The selected electric field intensity was 30, 40 and 50 kV/cm and the number of pulses applied was 10.6, 21.3 and 32. The sensitization exhibited by PEF treated L. innocua to nisin was assessed for 10 or 100 IU nisin/ml. A progressive decrease in the population of L. innocua was observed for the selected field intensities, with the greatest reduction being 2 1/2 log cycles (U). The exposure of L. innocua to nisin after PEF had an additive effect on the inactivation of the microorganism as that exhibited by the PEF alone. As the electric field, number of pulses and nisin concentration increased, synergism was observed in the inactivation of L. innocua as a result of exposure to nisin after PEF. The reduction of L. innocua accomplished by exposure to 10 IU nisin/ml after 32 pulsed electric fields was 2, 2.7, and 3.4 U for an electric field intensity of 30, 40, and 50 kV/cm, respectively. Population of L. innocua subjected to 100 IU nisin/ml after PEF was 2.8-3.8 U for the selected electric field intensities and 32 pulses. The designed model for the inactivation of L. innocua as a result of the PEF followed by exposure to nisin proved to be accurate in the prediction of the inactivation of L. innocua in skim milk containing 1.2 or 37 IU nisin/ml. Inactivation of L. innocua in skim milk containing 37 IU nisin/ml resulted in a decrease in population of 3.7 U.

  19. Incorporation of nisin in natural casing for the control of spoilage microorganisms in vacuum packaged sausage

    OpenAIRE

    Barros,Joyce Regina de; Kunigk,Leo; Jurkiewicz,Cynthia Hyppolito

    2010-01-01

    This study aimed to evaluate the effectiveness of natural casing treatment with nisin and phosphoric acid on control of spoilage microorganisms in vacuum packaged sausages. Ovine casings were dipped in the following baths: 1) 0.1% food grade phosphoric acid; 2) 5.0 mg/L nisin; 3)?0.1% phosphoric acid and 5.0 mg/L nisin; and 4) sterile water (control). The sausages were produced in a pilot plant, stuffed into the pretreated natural casings, vacuum packaged and stored at 4 and 10??C for 56 days...

  20. Targeting bacterial topoisomerases: how to counter mechanisms of resistance.

    Science.gov (United States)

    Tse-Dinh, Yuk-Ching

    2016-06-01

    DNA gyrase and topoisomerase IV are type IIA bacterial topoisomerases that are targeted by highly effective antibiotics. However, resistance via multiple mechanisms arises to limit the efficacies of these drugs. Continued research on type IIA bacterial topoisomerases has provided novel approaches to counter the most common resistance mechanism for utilization of these proven targets in antibacterial therapy. Bacterial topoisomerase I is being explored as an alternative target that is not expected to show cross-resistance. Dual targeting or combination therapy could be strategies for circumventing the development of resistance to topoisomerase-targeting antibiotics. Bacterial topoisomerases are high-value bactericidal targets that could continue to be exploited for antibacterial therapy, if new tactics to counter resistance can be adopted.

  1. Molecular Mechanisms of Chromium in Alleviating Insulin Resistance

    Science.gov (United States)

    Hua, Yinan; Clark, Suzanne; Ren, Jun; Sreejayan, Nair

    2011-01-01

    Type 2 diabetes is often associated with obesity, dyslipidemia, and cardiovascular anomalies and is a major health problem approaching global epidemic proportions. Insulin resistance, a prediabetic condition, precedes the onset of frank type 2 diabetes and offers potential avenues for early intervention to treat the disease. Although lifestyle modifications and exercise can reduce the incidence of diabetes, compliance has proved to be difficult, warranting pharmacological interventions. However, most of the currently available drugs that improve insulin sensitivity have adverse effects. Therefore, attractive strategies to alleviate insulin resistance include dietary supplements. One such supplement is chromium, which has been shown reduce insulin resistance in some, but not all, studies. Furthermore, the molecular mechanisms of chromium in alleviating insulin resistance remain elusive. This review examines emerging reports on the effect of chromium, as well as molecular and cellular mechanisms by which chromium may provide beneficial effects in alleviating insulin resistance. PMID:22423897

  2. Volume Resistivity and Mechanical Behavior of Epoxy Nanocomposite Materials

    Directory of Open Access Journals (Sweden)

    M. F. Abdelkarim

    2015-04-01

    Full Text Available Electrical and mechanical properties of polymer composite materials are investigated through the determination of resistivity and hardness for composites samples. Epoxy composite samples have been prepared with different concentrations of certain inorganic fillers such as; Titanium dioxide (TiO2 and Silica (SiO2, of various size (micro, nano and hybrid to study the electrical and mechanical behavior. The volume resistivity reaches 3.23×1014 ohm.cm for the micro silica composite. Surface of composite material has been mechanically examined by hardness test. The results show that the resistivity of microcomposites and nanocmposites are increased with the decrease of filler concentration. But the resistivity of hybrid composites is increased with the increase of filler concentration. Maximum hardness value was obtained from hybrid silica composite with 0.1% filler concentration.

  3. Cross-resistance, inheritance and biochemical mechanisms of imidacloprid resistance in B-biotype Bemisia tabaci.

    Science.gov (United States)

    Wang, Zhenyu; Yao, Mingde; Wu, Yidong

    2009-11-01

    The B-type Bemisia tabaci (Gennadius) has become established in many regions in China, and neonicotinoids are extensively used to control this pest. Imidacloprid resistance in a laboratory-selected strain of B-type B. tabaci was characterised in order to provide the basis for recommending resistance management tactics. The NJ-Imi strain of B-type B. tabaci was selected from the NJ strain with imidacloprid for 30 generations. The NJ-Imi strain exhibited 490-fold resistance to imidacloprid, high levels of cross-resistance to three other neonicotinoids, low levels of cross-resistance to monosultap, cartap and spinosad, but no cross-resistance to abamectin and cypermethrin. Imidacloprid resistance in the NJ-Imi strain was autosomal and semi-dominant. It is shown that enhanced detoxification mediated by cytochrome-P450-dependent monooxygenases contributes to imidacloprid resistance to some extent in the NJ-Imi strain. Results from synergist bioassays and cross-resistance patterns indicated that target-site insensitivity may be involved in imidacloprid resistance in the NJ-Imi strain of B. tabaci. Although oxidative detoxification mediated by P450 monooxygenases is involved in imidacloprid resistance in the NJ-Imi strain of B-type B. tabaci, target-site modification as an additional resistance mechanism cannot be ruled out. Considering the high risk of cross-resistance, neonicotinoids should be regarded as a single group when implementing an insecticide rotation scheme in B. tabaci control. (c) 2009 Society of Chemical Industry.

  4. Topoisomerase Inhibitors: Fluoroquinolone Mechanisms of Action and Resistance.

    Science.gov (United States)

    Hooper, David C; Jacoby, George A

    2016-09-01

    Quinolone antimicrobials are widely used in clinical medicine and are the only current class of agents that directly inhibit bacterial DNA synthesis. Quinolones dually target DNA gyrase and topoisomerase IV binding to specific domains and conformations so as to block DNA strand passage catalysis and stabilize DNA-enzyme complexes that block the DNA replication apparatus and generate double breaks in DNA that underlie their bactericidal activity. Resistance has emerged with clinical use of these agents and is common in some bacterial pathogens. Mechanisms of resistance include mutational alterations in drug target affinity and efflux pump expression and acquisition of resistance-conferring genes. Resistance mutations in one or both of the two drug target enzymes are commonly in a localized domain of the GyrA and ParC subunits of gyrase and topoisomerase IV, respectively, and reduce drug binding to the enzyme-DNA complex. Other resistance mutations occur in regulatory genes that control the expression of native efflux pumps localized in the bacterial membrane(s). These pumps have broad substrate profiles that include other antimicrobials as well as quinolones. Mutations of both types can accumulate with selection pressure and produce highly resistant strains. Resistance genes acquired on plasmids confer low-level resistance that promotes the selection of mutational high-level resistance. Plasmid-encoded resistance is because of Qnr proteins that protect the target enzymes from quinolone action, a mutant aminoglycoside-modifying enzyme that also modifies certain quinolones, and mobile efflux pumps. Plasmids with these mechanisms often encode additional antimicrobial resistances and can transfer multidrug resistance that includes quinolones. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  5. [Investigation of molecular mechanisms of aminoglycoside resistance in Salmonella].

    Science.gov (United States)

    Zubritskiĭ, A V; Il'ina, E N; Strel'chenko, S A; Malakhova, M V; Lenev, S V; Skliarov, O D; Panin, A N; Govorun, V M

    2011-01-01

    The spread of aminoglycoside resistance phenotype and respective genetic resistance determinants was evaluated in 243 Salmonella strains isolated within 1948-2010 and stored in the Culture Collection of the Russian State Research Institute for Control, Standardization and Certification of Veterinary Preparations (Moscow). The Salmonella strains showed resistance to streptomycin and gentamicin in 3.7% (n = 9) and 0.8% (n = 2) of the isolates respectively. Intermediate resistance to streptomycin was recorded in 9.9% (n = 24) of the isolates. To detect the genes responsible for the aminoglycoside resistance, primers for aadA1, aadA2, aadB, aphA1, aphA3, sat, strA, strB, aphA, aacC, rmtB, armA and rpsL genes amplification and sequencing were designed. The strains with lower susceptibility to streptomycin harbored aadA1, aadA2, strA, strB resistance genes encoding enzymes for aminoglicoside modification and rpsL mutant allele (K42N, G91D). Genetic mechanisms able to explain the gentamicin resistance development were not detected. Some strains carried genetic markers of streptomycine resistance but had no clinically sufficient resistance to it. In this regard, genetic testing is essential for prevention of drug resistance spreading due to horizontal transfer of genes in microbial population.

  6. Fiber-optic demultiplexers with high mechanical resistance

    Directory of Open Access Journals (Sweden)

    Yakovlev M. Ya.

    2011-04-01

    Full Text Available The paper observes possibilities of fused fiber-optic multiplexer-demultiplexer creation with resistance to mechanical effect. Fabrication method and the equipment for their production are presented. Resonant frequency of weld area mechanical oscillations dependences from fused fiber-optic demultiplexer design characteristics are investigated.

  7. Identification of Mechanical parameters for Resistance Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels

    2003-01-01

    Mechanical dynamic responses of resistance welding machine have a significant influence on weld quality and electrode service life, it must be considered when the real welding production is carried out or the welding process is simulated. The mathematical models for characterizing the mechanical ...

  8. Characterisation of glufosinate resistance mechanisms in Eleusine indica.

    Science.gov (United States)

    Jalaludin, Adam; Yu, Qin; Zoellner, Peter; Beffa, Roland; Powles, Stephen B

    2017-06-01

    An Eleusine indica population has evolved resistance to glufosinate, a major post-emergence herbicide of global agriculture. This population was analysed for target-site (glutamine synthetase) and non-target-site (glufosinate uptake, translocation and metabolism) resistance mechanisms. Glutamine synthetase (GS) activity extracted from susceptible (S) and resistant (R*) plants was equally sensitive to glufosinate inhibition, with IC 50 values of 0.85 mm and 0.99 mm, respectively. The extractable GS activity was also similar in S and R* samples. Foliar uptake of [ 14 C]-glufosinate did not differ in S and R* plants, nor did glufosinate net uptake in leaf discs. Translocation of [ 14 C]-glufosinate into untreated shoots and roots was also similar in both populations, with 44% to 47% of the herbicide translocated out from the treated leaf 24 h after treatment. The HPLC and LC-MS analysis of glufosinate metabolism revealed no major metabolites in S or R* leaf tissue. Glufosinate resistance in this resistant population is not due to an insensitive GS, or increased activity, or altered glufosinate uptake and translocation, or enhanced glufosinate metabolism. Thus, target-site resistance is likely excluded and the exact resistance mechanism(s) remain to be determined. © 2017 Society of Chemical Industry. © 2017 Society of Chemical Industry.

  9. Resistance Mechanisms of Anopheles stephensi (Diptera: Culicidae to Temephos

    Directory of Open Access Journals (Sweden)

    Aboozar Soltani

    2015-10-01

    Full Text Available Background: Anopheles stephensi is a sub-tropical species and has been considered as one of the most important vector of human malaria throughout the Middle East and South Asian region including the malarious areas of southern Iran. Current reports confirmed An. stephensi resistance to temephos in Oman and India. However, there is no comprehensive research on mechanisms of temephos resistance in An. stephensi in the literature. This study was designed in order to clarify the enzymatic and molecular mechanisms of temephos resistance in this species.Methods: Profile activities of α- and ß-esterases, mixed function oxidase (MFO, glutathione-S-transferase (GST, insensitive acetylcholinesterase, and para-nitrophenyl acetate (PNPA-esterase enzymes were tested for An. stephensi strain with resistance ratio of 15.82 to temephos in comparison with susceptible strain.Results: Results showed that the mean activity of α-EST, GST and AChE enzymes were classified as altered indicating metabolic mechanisms have considerable role in resistance of An. stephensi to temephos. Molecular study using PCR-RFLP method to trace the G119S mutation in ACE-1 gene showed lack of the mutation responsible for organophosphate insecticide resistance in the temephos-selected strain of An. stephensi.Conclusion: This study showed that the altered enzymes but not targets site insensitivity of ACE-1 are responsible for temephos resistance in An. stephensi in south of Iran.

  10. Mechanisms of antimicrobial resistance among hospital-associated pathogens.

    Science.gov (United States)

    Khan, Ayesha; Miller, William R; Arias, Cesar A

    2018-04-01

    The introduction of antibiotics revolutionized medicine in the 20th-century permitting the treatment of once incurable infections. Widespread use of antibiotics, however, has led to the development of resistant organisms, particularly in the healthcare setting. Today, the clinician is often faced with pathogens carrying a cadre of resistance determinants that severely limit therapeutic options. The genetic plasticity of microbes allows them to adapt to stressors via genetic mutations, acquisition or sharing of genetic material and modulation of genetic expression leading to resistance to virtually any antimicrobial used in clinical practice. Areas covered: This is a comprehensive review that outlines major mechanisms of resistance in the most common hospital-associated pathogens including bacteria and fungi. Expert commentary: Understanding the genetic and biochemical mechanisms of such antimicrobial adaptation is crucial to tackling the rapid spread of resistance, can expose unconventional therapeutic targets to combat multidrug resistant pathogens and lead to more accurate prediction of antimicrobial susceptibility using rapid molecular diagnostics. Clinicians making treatment decisions based on the molecular basis of resistance may design therapeutic strategies that include de-escalation of broad spectrum antimicrobial usage, more focused therapies or combination therapies. These strategies are likely to improve patient outcomes and decrease the risk of resistance in hospital settings.

  11. Different mechanisms of resistance modulate sulfite tolerance in wine yeasts.

    Science.gov (United States)

    Nadai, Chiara; Treu, Laura; Campanaro, Stefano; Giacomini, Alessio; Corich, Viviana

    2016-01-01

    From a technological point of view, yeast resistance to sulfite is of great interest and represents an important technological character for winemaking. Several mechanisms are involved, and strain-dependent strategies to obtain SO2 resistance can deeply influence wine quality, although this choice is less relevant in determining the technological performance of the strain during fermentation. In this study, to better understand the strain-specific mechanisms of resistance, 11 Saccharomyces cerevisiae strains, whose genomes have been previously sequenced, were selected. Their attitude towards sulfites, in terms of resistance and production, was evaluated, and RNA-sequencing of four selected strains was performed during fermentation process in synthetic grape must in the presence of SO2. Results demonstrated that at molecular level, the physical effect of SO2 triggered multiple stress responses in the cell and high tolerance to general enological stressing condition increased SO2 resistance. Adaptation mechanism due to high basal gene expression level rather than specific gene induction in the presence of sulfite seemed to be responsible in modulating strain resistance. This mechanism involved higher basal gene expression level of specific cell wall proteins, enzymes for lipid biosynthesis, and enzymes directly involved in SO2 assimilation pathway and efflux.

  12. Mechanisms of hormonal therapy resistance in breast cancer.

    Science.gov (United States)

    Hayashi, Shin-ichi; Kimura, Mariko

    2015-04-01

    Whilst estrogen receptor (ER)-positive breast cancers are preferentially treated with hormone therapy, approximately one-third of them relapse. The mechanisms of refractoriness have been investigated by numerous studies but have not been fully clarified. Hormonal therapy resistance, particularly aromatase inhibitor (AI) resistance, may be related to the acquisition of alternative intracellular ER signaling. We have been investing the mechanisms using cancer specimens and cell lines by monitoring the transcription activity of ERs. AI refractory specimens showed diverse ER activity in the adenovirus estrogen receptor element-green fluorescent protein (ERE-GFP) assay and varied sensitivity to anti-estrogens, indicating the existence of multiple resistant mechanisms. We established six different types of cell lines mimicking AI resistance from ERE-GFP-introduced ER-positive cell lines. They revealed that multiple and alternative ER activating pathways were involved in the resistance, such as phosphorylation-dependent or androgen metabolite-dependent mechanisms. The response to fulvestrant and mammalian target of rapamycin inhibitor also varied among individual resistant cell lines. These results indicate that further subclassification of ER-positive breast cancer is extremely important to decide the therapeutic management of not only hormonal therapy but also new molecular target therapy.

  13. Cationic antimicrobial peptide resistance mechanisms of streptococcal pathogens.

    Science.gov (United States)

    LaRock, Christopher N; Nizet, Victor

    2015-11-01

    Cationic antimicrobial peptides (CAMPs) are critical front line contributors to host defense against invasive bacterial infection. These immune factors have direct killing activity toward microbes, but many pathogens are able to resist their effects. Group A Streptococcus, group B Streptococcus and Streptococcus pneumoniae are among the most common pathogens of humans and display a variety of phenotypic adaptations to resist CAMPs. Common themes of CAMP resistance mechanisms among the pathogenic streptococci are repulsion, sequestration, export, and destruction. Each pathogen has a different array of CAMP-resistant mechanisms, with invasive disease potential reflecting the utilization of several mechanisms that may act in synergy. Here we discuss recent progress in identifying the sources of CAMP resistance in the medically important Streptococcus genus. Further study of these mechanisms can contribute to our understanding of streptococcal pathogenesis, and may provide new therapeutic targets for therapy and disease prevention. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Mechanisms of lichen resistance to metallic pollution

    Energy Technology Data Exchange (ETDEWEB)

    Sarret, C.; Manceau, A.; Eybert-Berard, L. [Univ. of Grenoble and CNRS (France). Environmental Geochemistry Group; Cuny, D.; Haluwyn, C. van [Lab. de Botanique et de Cryptogamie, Lille (France); Deruelle, S. [Institut d`Ecologie, Paris (France); Hazemann, J.L.; Menthonnex, J.J. [Univ. of Grenoble and CNRS (France). Environmental Geochemistry Group]|[CNRS, Grenoble (France). Lab. de Cristallographie; Soldo, Y. [CNRS, Grenoble (France). Lab. de Cristallographie

    1998-11-01

    Some lichens have a unique ability to grow in heavily contaminated areas due to the development of adaptative mechanisms allowing a high tolerance to metals. Here the authors report on the chemical forms of Pb and Zn in the metal hyperaccumulator Diploschistes muscorum and of Pb in the metal tolerant lichen Xanthoria parietina. The speciation of Zn and Pb has been investigated by powder X-ray diffraction (XRD) and extended X-ray absorption fine structure (EXAFS) spectroscopy using the advanced third-generation synchrotron radiation source of the European synchrotron radiation facility (ESRF in Grenoble). This study reveals that in both lichens cells are protected from toxicity by complexation of heavy metals, but the strategies differ: in D. muscorum, Pb and Zn are accumulated through an enhanced synthesis of oxalate, which precipitates toxic elements as insoluble salts, whereas in X. parietina, Pb is complexed to carboxylic groups of the fungal cell walls. The authors conclude that hyperaccumulation of metals results from a reactive mechanism of organic acid production, whereas metallo-tolerance is achieved by a passive complexation to existing functional groups.

  15. Multidrug-Resistant Candida: Epidemiology, Molecular Mechanisms, and Treatment.

    Science.gov (United States)

    Arendrup, Maiken Cavling; Patterson, Thomas F

    2017-08-15

    Invasive Candida infections remain an important cause of morbidity and mortality, especially in hospitalized and immunocompromised or critically ill patients. A limited number of antifungal agents from only a few drug classes are available to treat patients with these serious infections. Resistance can be either intrinsic or acquired. Resistance mechanisms are not exchanged between Candida; thus, acquired resistance either emerges in response to an antifungal selection pressure in the individual patient or, more rarely, occur due to horizontal transmission of resistant strains between patients. Although multidrug resistance is uncommon, increasing reports of multidrug resistance to the azoles, echinocandins, and polyenes have occurred in several Candida species, most notably Candida glabrata and more recently Candida auris. Drivers are overall antifungal use, subtherapeutic drug levels at sites of infection/colonization, drug sequestration in the biofilm matrix, and, in the setting of outbreaks, suboptimal infection control. Moreover, recent research suggests that DNA mismatch repair gene mutations may facilitate acquisition of resistance mutations in C. glabrata specifically. Diagnosis of antifungal-resistant Candida infections is critical to the successful management of patients with these infections. Reduction of unnecessary use of antifungals via antifungal stewardship is critical to limit multidrug resistance emergence. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  16. Multidrug resistance in cancer: its mechanism and its modulation.

    Science.gov (United States)

    Pauwels, Ernest K J; Erba, Paula; Mariani, Giuliano; Gomes, Célia M F

    2007-01-01

    One of the major problems related with the curative treatment of cancer patients is resistance against anticancer drugs. This resistance, which may occur from the beginning or is evident only later as an acquired phenomenon, is due to the action of drug transporters. These transmembrane proteins belong to the ATP-binding cassette (ABC) transporters which reduce bioavailability of drugs, but also determine the elimination of xenobiotics into bile, urine and feces. The present review summarizes recent knowledge in this area, highlighting the mechanism of action of these transporters, its clinical significance and its possible modulation. Novel approaches to overcome multidrug resistance include agents which inhibit or circumvent this efflux mechanism. For the latter category developments in nanomedicine may be of consequence. However, in spite of considerable progress in research regarding multidrug resistance, the phase of efficacious clinical use of this knowledge has not been reached yet. (c) 2007 Prous Science. All rights reserved.

  17. Diversity and evolution of drug resistance mechanisms in Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Al-Saeedi M

    2017-10-01

    Full Text Available Mashael Al-Saeedi, Sahal Al-Hajoj Department of Infection and Immunity, Mycobacteriology Research Section, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia Abstract: Despite the efficacy of antibiotics to protect humankind against many deadly pathogens, such as Mycobacterium tuberculosis, nothing can prevent the emergence of drug-resistant strains. Several mechanisms facilitate drug resistance in M. tuberculosis including compensatory evolution, epistasis, clonal interference, cell wall integrity, efflux pumps, and target mimicry. In this study, we present recent findings relevant to these mechanisms, which can enable the discovery of new drug targets and subsequent development of novel drugs for treatment of drug-resistant M. tuberculosis. Keywords: Mycobacterium tuberculosis, antibiotic resistance, compensatory evolution, epistasis, efflux pumps, fitness cost

  18. Dietary Nisin Modulates the Gastrointestinal Microbial Ecology and Enhances Growth Performance of the Broiler Chickens

    Science.gov (United States)

    Józefiak, Damian; Kierończyk, Bartosz; Juśkiewicz, Jerzy; Zduńczyk, Zenon; Rawski, Mateusz; Długosz, Jakub; Sip, Anna; Højberg, Ole

    2013-01-01

    Due to antimicrobial properties, nisin is one of the most commonly used and investigated bacteriocins for food preservation. Surprisingly, nisin has had limited use in animal feed as well as there are only few reports on its influence on microbial ecology of the gastrointestinal tract (GIT). The present study therefore aimed at investigating effects of dietary nisin on broiler chicken GIT microbial ecology and performance in comparison to salinomycin, the widely used ionophore coccidiostat. In total, 720 one-day-old male Ross 308 chicks were randomly distributed to six experimental groups. The positive control (PC) diet was supplemented with salinomycin (60 mg/kg). The nisin (NI) diets were supplemented with increasing levels (100, 300, 900 and 2700 IU nisin/g, respectively) of the bacteriocin. The negative control (NC) diet contained no additives. At slaughter (35 days of age), activity of specific bacterial enzymes (α- and β-glucosidases, α-galactosidases and β-glucuronidase) in crop, ileum and caeca were significantly higher (Penzyme activities to levels observed for the PC group. A similar inhibitory influence on bacterial activity was reflected in the levels of short-chain fatty acids (SCFA) and putrefactive SCFA (PSCFA) in digesta from crop and ileum; no effect was observed in caeca. Counts of Bacteroides and Enterobacteriacae in ileum digesta were significantly (P<0.001) decreased by nisin and salinomycin, but no effects were observed on the counts of Clostridium perfringens, Lactobacillus/Enterococcus and total bacteria. Like salinomycin, nisin supplementation improved broiler growth performance in a dose-dependent manner; compared to the NC group, the body weight gain of the NI900 and NI2700 groups was improved by 4.7 and 8.7%, respectively. Our findings suggest that dietary nisin exerts a mode of action similar to salinomycin and could be considered as a dietary supplement for broiler chickens. PMID:24376878

  19. Effects of combined exposure of Micrococcus luteus to nisin and pulsed electric fields

    NARCIS (Netherlands)

    Dutreux, N.; Notermans, S.; Góngora-Nieto, M.M.; Barbosa-Cánovas, G.V.; Swanson, B.G.

    2000-01-01

    Death and injury following exposure of Micrococcus luteus to nisin and pulsed electric field (PEF) treatment were investigated in phosphate buffer (pH 6.8, σ = 4.8 ms/cm at 20°C). Four types of experiment were carried out, a single treatment with nisin (100 IU/ml at 20°C for 2 h), a single PEF

  20. Combinations of nisin with salt (NaCl) to control Listeria ...

    African Journals Online (AJOL)

    This study evaluated the effect of combinations of nisin with salt (NaCl) to control Listeria monocytogenes on sheep natural sausage casings. Casings were inoculated with 3.0 x 105 cfu/g final inocula of L. monocytogenes, stored at 6°C in different solutions of nisin at 0, 100, 150 and 200 ìg/g. Each combined with salt at 0, 4, ...

  1. Inhibitory Effect of Nisin on Listeria monocytogenes Inoculated into Surimi and Minced Meat

    Directory of Open Access Journals (Sweden)

    Masoud Rezaei

    2012-02-01

    Full Text Available Background & Objective: Listeria monocytogenes has already established as an important food born pathogen which induce listeriosis in human. Use of bacteriocins to provide food safety has been increased dramatically. Nisin has a wide spectrum inhibitory effect than the other bacteriocins and inhibits food-borne pathogens such as L. monocytogenes and many other Gram-positive spoilage microorganisms. The purpose of this study was to investigate the inhibitory effect of Nisin on population of Listeria monocytogenes and the role of changes in food components on the antilisterial properties of Nisin. Materials & Methods: The minced meat and surimi samples were inoculated by 1×104 cfu/g of L. monocytogenes. Then samples exposed to Nisin at the levels of 500 or 1000 IU/g were prepared. All treatments after packaging in plastic bags were kept for 12 days at refrigerator temperature. Samples were cultured on CHROMagarTM Listeria every 2 days and the number of listeria monocytogenes was counted. Results: two different concentrations of Nisin (500 or 1000 IU/g was not able to inhibit L. monocytogenes below the acceptable level for raw food (100 cells per g in minced meat and surimi of silver carp. But the number of bacteria reduces more in fish surimi as compared to the mince meal. Also, antilisterial activity of Nisin was reduced during the storage period. Conclusion: Inhibitory property of Nisin against L. monocytogenes in surimi significantly was higher than the minced (P<0.05. So it is possible the antilisterial properties of Nisin will increase by elimination of some enzymes during processing.

  2. Treatment Resistance Mechanisms of Malignant Glioma Tumor Stem Cells

    International Nuclear Information System (INIS)

    Schmalz, Philip G.R.; Shen, Michael J.; Park, John K.

    2011-01-01

    Malignant gliomas are highly lethal because of their resistance to conventional treatments. Recent evidence suggests that a minor subpopulation of cells with stem cell properties reside within these tumors. These tumor stem cells are more resistant to radiation and chemotherapies than their counterpart differentiated tumor cells and may underlie the persistence and recurrence of tumors following treatment. The various mechanisms by which tumor stem cells avoid or repair the damaging effects of cancer therapies are discussed

  3. An Evolutionarily Conserved Mechanism for Intrinsic and Transferable Polymyxin Resistance.

    Science.gov (United States)

    Xu, Yongchang; Wei, Wenhui; Lei, Sheng; Lin, Jingxia; Srinivas, Swaminath; Feng, Youjun

    2018-04-10

    Polymyxins, a family of cationic antimicrobial cyclic peptides, act as a last line of defense against severe infections by Gram-negative pathogens with carbapenem resistance. In addition to the intrinsic resistance to polymyxin E (colistin) conferred by Neisseria eptA , the plasmid-borne mobilized colistin resistance gene mcr-1 has been disseminated globally since the first discovery in Southern China, in late 2015. However, the molecular mechanisms for both intrinsic and transferable resistance to colistin remain largely unknown. Here, we aim to address this gap in the knowledge of these proteins. Structural and functional analyses of EptA and MCR-1 and -2 have defined a conserved 12-residue cavity that is required for the entry of the lipid substrate, phosphatidylethanolamine (PE). The in vitro and in vivo data together have allowed us to visualize the similarities in catalytic activity shared by EptA and MCR-1 and -2. The expression of either EptA or MCR-1 or -2 is shown to remodel the surface of enteric bacteria (e.g., Escherichia coli , Salmonella enterica , Klebsiella pneumoniae , etc.), rendering them resistant to colistin. The parallels in the PE substrate-binding cavities among EptA, MCR-1, and MCR-2 provide a comprehensive understanding of both intrinsic and transferable colistin resistance. Domain swapping between EptA and MCR-1 and -2 reveals that the two domains (transmembrane [TM] region and p hospho e thanol a mine [PEA] transferase) are not functionally exchangeable. Taken together, the results represent a common mechanism for intrinsic and transferable PEA resistance to polymyxin, a last-resort antibiotic against multidrug-resistant pathogens. IMPORTANCE EptA and MCR-1 and -2 remodel the outer membrane, rendering bacteria resistant to colistin, a final resort against carbapenem-resistant pathogens. Structural and functional analyses of EptA and MCR-1 and -2 reveal parallel PE lipid substrate-recognizing cavities, which explains intrinsic and

  4. Effect of different concentrations of nisin on starter culture of model Cheeses manufactured from ultrafiltrated milk

    Directory of Open Access Journals (Sweden)

    Kh Mohammadi

    2013-05-01

    Full Text Available Nisin is a natural preservative produced by strains of Lactococcuslactis subsp. Lactis, has been approved for use in food by the Joint Food and Agricultural Organization/World Health Organization (FAO/WHO Committee on Food Additives and has been awarded generally recognized as safe (GRAS. It remains the only bacteriocin allowed in food as an addedpreservative. Nisin has a broad spectrum of antimicrobial activity againstgram-positive bacteria, thus one of the problems associated with nisin application is inhibition of starter culture and prevention of ripening, which is required for development of cheese characteristics during ripening. In the current study, the effects of different concentrations of nisin and temperature on growth and activity of lactic acid bacteria in model cheeses manufactured from ultrafiltrated milk was evaluated. Cheese samples were supplemented with nisin at concentrations of 0, 2, 4 and 6 µg/g and stored at 8 and 25 °C up to 60 days. Microbiological and physico-chemical properties of the cheese samples were analyzedat 0, 1, 8, 15, 30, 45 and 60 days. Results showed that addition of nisin at concentrations of 4 and 6 µg/g affects (p

  5. Incorporation of nisin in natural casing for the control of spoilage microorganisms in vacuum packaged sausage.

    Science.gov (United States)

    de Barros, Joyce Regina; Kunigk, Leo; Jurkiewicz, Cynthia Hyppolito

    2010-10-01

    This study aimed to evaluate the effectiveness of natural casing treatment with nisin and phosphoric acid on control of spoilage microorganisms in vacuum packaged sausages. Ovine casings were dipped in the following baths: 1) 0.1% food grade phosphoric acid; 2) 5.0 mg/L nisin; 3) 0.1% phosphoric acid and 5.0 mg/L nisin; and 4) sterile water (control). The sausages were produced in a pilot plant, stuffed into the pretreated natural casings, vacuum packaged and stored at 4 and 10 °C for 56 days. The experiments were performed according to a full factorial design 2(3), totalizing 8 treatments that were repeated in 3 blocks. Aerobic plate counts and lactic acid bacteria analysis were conducted at 1, 14, 28, 42 and 56 days of storage. Treatment of casings with phosphoric acid 0.1% alone did not inhibit the growth of lactic acid bacteria and reduced the aerobic plate count by 1 log. The activity of nisin against lactic acid bacteria was enhanced by the addition of phosphoric acid, demonstrating a synergistic effect. Furthermore nisin activity was more evident at lower storage temperature (4 ºC). Therefore treatment of the natural casings with nisin and phosphoric acid, combined with low storage temperature, are obstacles that present a potential for controlling the growth of lactic acid bacteria in vacuum packaged sausage.

  6. Incorporation of nisin in natural casing for the control of spoilage microorganisms in vacuum packaged sausage

    Directory of Open Access Journals (Sweden)

    Joyce Regina de Barros

    2010-12-01

    Full Text Available This study aimed to evaluate the effectiveness of natural casing treatment with nisin and phosphoric acid on control of spoilage microorganisms in vacuum packaged sausages. Ovine casings were dipped in the following baths: 1 0.1% food grade phosphoric acid; 2 5.0 mg/L nisin; 3 0.1% phosphoric acid and 5.0 mg/L nisin; and 4 sterile water (control. The sausages were produced in a pilot plant, stuffed into the pretreated natural casings, vacuum packaged and stored at 4 and 10 °C for 56 days. The experiments were performed according to a full factorial design 2³, totalizing 8 treatments that were repeated in 3 blocks. Aerobic plate counts and lactic acid bacteria analysis were conducted at 1, 14, 28, 42 and 56 days of storage. Treatment of casings with phosphoric acid 0.1% alone did not inhibit the growth of lactic acid bacteria and reduced the aerobic plate count by 1 log. The activity of nisin against lactic acid bacteria was enhanced by the addition of phosphoric acid, demonstrating a synergistic effect. Furthermore nisin activity was more evident at lower storage temperature (4 ºC. Therefore treatment of the natural casings with nisin and phosphoric acid, combined with low storage temperature, are obstacles that present a potential for controlling the growth of lactic acid bacteria in vacuum packaged sausage.

  7. Pathophysiological mechanisms of death resistance in colorectal carcinoma.

    Science.gov (United States)

    Huang, Ching-Ying; Yu, Linda Chia-Hui

    2015-11-07

    Colon cancers develop adaptive mechanisms to survive under extreme conditions and display hallmarks of unlimited proliferation and resistance to cell death. The deregulation of cell death is a key factor that contributes to chemoresistance in tumors. In a physiological context, balance between cell proliferation and death, and protection against cell damage are fundamental processes for maintaining gut epithelial homeostasis. The mechanisms underlying anti-death cytoprotection and tumor resistance often bear common pathways, and although distinguishing them would be a challenge, it would also provide an opportunity to develop advanced anti-cancer therapeutics. This review will outline cell death pathways (i.e., apoptosis, necrosis, and necroptosis), and discuss cytoprotective strategies in normal intestinal epithelium and death resistance mechanisms of colon tumor. In colorectal cancers, the intracellular mechanisms of death resistance include the direct alteration of apoptotic and necroptotic machinery and the upstream events modulating death effectors such as tumor suppressor gene inactivation and pro-survival signaling pathways. The autocrine, paracrine and exogenous factors within a tumor microenvironment can also instigate resistance against apoptotic and necroptotic cell death in colon cancers through changes in receptor signaling or transporter uptake. The roles of cyclooxygenase-2/prostaglandin E2, growth factors, glucose, and bacterial lipopolysaccharides in colorectal cancer will be highlighted. Targeting anti-death pathways in the colon cancer tissue might be a promising approach outside of anti-proliferation and anti-angiogenesis strategies for developing novel drugs to treat refractory tumors.

  8. Antimicrobial properties of nisin after glycation with lactose, maltodextrin and dextran and the thyme oil emulsions prepared thereof.

    Science.gov (United States)

    Chen, Huaiqiong; Davidson, P Michael; Zhong, Qixin

    2014-11-17

    To clarify the reported conflicting antimicrobial activities of nisin after glycation, nisin was glycated with lactose, maltodextrin, and dextran at 70 °C and 50% relative humidity for 1-24 h. Nisin before and after glycation was studied for the first time to prepare thyme oil emulsions. The activity of glycated nisin and the thyme oil emulsions was tested in both tryptic soy broth (TSB) and 2% reduced fat milk. Results showed that nisin glycated with a smaller saccharide for a longer duration had a higher degree of glycation and the reduced number of positive charges lowered its antibacterial activity. The emulsified thyme oil had an additive effect with either glycated or native nisin against Listeria monocytogenes Scott A and Bacillus subtilis in TSB and 2% reduced fat milk. However, emulsions were less effective against L. monocytogenes Scott A in milk than same units of native nisin and same concentration of free thyme oil, likely due to the reduced availability of thymol and carvacrol, the main components of thyme oil. These results showed that glycation of nisin cannot broaden its antimicrobial activity and nisin is not a good compound to prepare emulsions of essential oils. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Mechanisms of resistance to decitabine in the myelodysplastic syndrome.

    Directory of Open Access Journals (Sweden)

    Taichun Qin

    Full Text Available The DNA methylation inhibitor 5-aza-2'-deoxycytidine (DAC is approved for the treatment of myelodysplastic syndromes (MDS, but resistance to DAC develops during treatment and mechanisms of resistance remain unknown. Therefore, we investigated mechanisms of primary and secondary resistance to DAC in MDS.We performed Quantitative Real-Time PCR to examine expression of genes related to DAC metabolism prior to therapy in 32 responders and non-responders with MDS as well as 14 patients who achieved a complete remission and subsequently relapsed while on therapy (secondary resistance. We then performed quantitative methylation analyses by bisulfite pyrosequencing of 10 genes as well as Methylated CpG Island Amplification Microarray (MCAM analysis of global methylation in secondary resistance.Most genes showed no differences by response, but the CDA/DCK ratio was 3 fold higher in non-responders than responders (P<.05, suggesting that this could be a mechanism of primary resistance. There were no significant differences at relapse in DAC metabolism genes, and no DCK mutations were detected. Global methylation measured by the LINE1 assay was lower at relapse than at diagnosis (P<.05. On average, the methylation of 10 genes was lower at relapse (16.1% compared to diagnosis (18.1% (P<.05. MCAM analysis showed decreased methylation of an average of 4.5% (range 0.6%-9.7% of the genes at relapse. By contrast, new cytogenetic changes were found in 20% of patients.Pharmacological mechanisms are involved in primary resistance to DAC, whereas hypomethylation does not prevent a relapse for patients with DAC treatment.

  10. Microbial Resistance Mechanisms to the Antibiotic and Phytotoxin Fusaric Acid.

    Science.gov (United States)

    Crutcher, Frankie K; Puckhaber, Lorraine S; Stipanovic, Robert D; Bell, Alois A; Nichols, Robert L; Lawrence, Katheryn S; Liu, Jinggao

    2017-10-01

    Fusaric acid (FA) produced by Fusarium oxysporum plays an important role in disease development in plants, including cotton. This non-specific toxin also has antibiotic effects on microorganisms. Thus, one expects a potential pool of diverse detoxification mechanisms of FA in nature. Bacteria and fungi from soils infested with Fusarium and from laboratory sources were evaluated for their ability to grow in the presence of FA and to alter the structure of FA into less toxic compounds. None of the bacterial strains were able to chemically modify FA. Highly FA-resistant strains were found only in Gram-negative bacteria, mainly in the genus of Pseudomonas. The FA resistance of the Gram-negative bacteria was positively correlated with the number of predicted genes for FA efflux pumps present in the genome. Phylogenetic analysis of predicted FA resistance proteins (FUSC, an inner membrane transporter component of the efflux pump) revealed that FUSC proteins having high sequence identities with the functionally characterized FA resistance protein FusC or Fdt might be the major contributors of FA resistance. In contrast, most fungi converted FA to less toxic compounds regardless of the level of FA resistance they exhibited. Five derivatives were detected, and the detoxification of FA involved either oxidative reactions on the butyl side chain or reductive reactions on the carboxylic acid group. The production of these metabolites from widely different phyla indicates that resistance to FA by altering its structure is highly conserved. A few FA resistant saprophytic or biocontrol strains of fungi were incapable of altering FA, indicating a possible involvement of efflux transporters. Deployment of both efflux and derivatization mechanisms may be a common feature of fungal FA resistance.

  11. Resistance Status and Resistance Mechanisms in a Strain of Aedes aegypti (Diptera: Culicidae) From Puerto Rico.

    Science.gov (United States)

    Estep, Alden S; Sanscrainte, Neil D; Waits, Christy M; Louton, Jessica E; Becnel, James J

    2017-11-07

    Puerto Rico (PR) has a long history of vector-borne disease and insecticide-resistant Aedes aegypti (L.). Defining contributing mechanisms behind phenotypic resistance is critical for effective vector control intervention. However, previous studies from PR have each focused on only one mechanism of pyrethroid resistance. This study examines the contribution of P450-mediated enzymatic detoxification and sodium channel target site changes to the overall resistance phenotype of Ae. aegypti collected from San Juan, PR, in 2012. Screening of a panel of toxicants found broad resistance relative to the lab susceptible Orlando (ORL1952) strain. We identified significant resistance to representative Type I, Type II, and nonester pyrethroids, a sodium channel blocker, and a sodium channel blocking inhibitor, all of which interact with the sodium channel. Testing of fipronil, a chloride channel agonist, also showed low but significant levels of resistance. In contrast, the PR and ORL1952 strains were equally susceptible to chlorfenapyr, which has been suggested as an alternative public health insecticide. Molecular characterization of the strain indicated that two common sodium channel mutations were fixed in the population. Topical bioassay with piperonyl butoxide (PBO) indicated cytochrome P450-mediated detoxification accounts for approximately half of the resistance profile. Transcript expression screening of cytochrome P450s and glutathione-S-transferases identified the presence of overexpressed transcripts. This study of Puerto Rican Ae. aegypti with significant contributions from both genetic changes and enzymatic detoxification highlights the necessity of monitoring for resistance but also defining the multiple resistance mechanisms to inform effective mosquito control. Published by Oxford University Press on behalf of Entomological Society of America 2017. This work is written by US Government employees and is in the public domain in the US.

  12. Mechanisms of Helicobacter pylori antibiotic resistance and molecular testing

    Directory of Open Access Journals (Sweden)

    Toshihiro eNishizawa

    2014-10-01

    Full Text Available Antibiotic resistance in Helicobacter pylori (H. pylori is the main factor affecting the efficacy of current treatment methods against infection caused by this organism. The traditional culture methods for testing bacterial susceptibility to antibiotics are expensive and require 10 to 14 days. Since resistance to clarithromycin, fluoroquinolone, and tetracycline seems to be exclusively caused by specific mutations in a small region of the responsible gene, molecular methods offer an attractive alternative to the above-mentioned techniques. The technique of polymerase chain reaction (PCR is an accurate and rapid method for the detection of mutations that confer antibiotic resistance. This review highlights the mechanisms of antibiotic resistance in H. pylori and the molecular methods for antibiotic susceptibility testing.

  13. Mechanisms of resistance to HER2 target therapy.

    Science.gov (United States)

    Tortora, Giampaolo

    2011-01-01

    In the past years, several agents targeting signaling proteins critical for breast cancer growth and dissemination entered clinical evaluation. They include drugs directed against the HER/ErbB family of receptor tyrosine kinases, especially HER2; several downstream signal transducers; and proteins involved in tumor angiogenesis and dissemination. Unfortunately, resistance to targeted agents is a quite common feature, and understanding of the molecular mechanisms predicting response or failure has become a crucial issue to optimize treatment and select patients who are the best candidates to respond. The neoadjuvant setting offers unique opportunities allowing tumor sampling and search for molecular determinants of response. A variety of tumor and host factors may account for the onset of resistance. Major progress has been made in the understanding of the mechanisms involved in the primary and acquired resistance to targeted agents, especially the anti-HER2 drugs, which play a pivotal role in the weaponry against breast cancer.

  14. The operational mechanism of ferroelectric-driven organic resistive switches

    NARCIS (Netherlands)

    Kemerink, M.; Asadi, K.; Blom, P.W.M.; Leeuw, D.M. de

    2012-01-01

    The availability of a reliable memory element is crucial for the fabrication of 'plastic' logic circuits. We use numerical simulations to show that the switching mechanism of ferroelectric-driven organic resistive switches is the stray field of the polarized ferroelectric phase. The stray field

  15. mechanisms of drought resistance in grain ii:.stomatal regulation ...

    African Journals Online (AJOL)

    Preferred Customer

    ABSTRACT: Earlier research works conducted to identify mechanisms of drought resistance in grain legumes under soil ... maintenance of high plant water potential in common bean under stress was the function of stomatal regulation and/or root ..... available only for maintenance requirements of the plant. On the other ...

  16. The operational mechanism of ferroelectric-driven organic resistive switches

    NARCIS (Netherlands)

    Kemerink, Martijn; Asadi, Kamal; Blom, Paul W. M.; de Leeuw, Dago M.

    The availability of a reliable memory element is crucial for the fabrication of 'plastic' logic circuits. We use numerical simulations to show that the switching mechanism of ferroelectric-driven organic resistive switches is the stray field of the polarized ferroelectric phase. The stray field

  17. Plant resistance to cold stress: Mechanisms and environmental ...

    Indian Academy of Sciences (India)

    Unknown

    temperature was an even more effective signal than day-length. [Beck E H, Heim R and Hansen J 2004 Plant resistance to cold stress: Mechanisms and environmental signals triggering frost hardening and dehardening; J. Biosci. 29 449–459]. 1. Introduction. 1.1 Ecophysiological aspects of plant cold stress and acclimation.

  18. Mechanical and electrical properties of resistance welds at cryogenic temperatures

    Energy Technology Data Exchange (ETDEWEB)

    Wang, S T; Kim, S H; Kim, N S; Ludwig, H

    1979-01-01

    The mechanical and electrical properties of resistance welds at cryogenic temperatures for the large superconducting magnet such as the superconducting MHD Dipole system for the National Coal-Fired Flow Facility (CFFF SCMS) at the U. of Tennessee Space Institute are reported.

  19. Cross-resistance of bisultap resistant strain of Nilaparvata lugens and its biochemical mechanism.

    Science.gov (United States)

    Ling, Shanfeng; Zhang, Runjie

    2011-02-01

    The resistant (R) strain of the planthopper Nilaparvata lugens (Stål) selected for bisultap resistance displayed 7.7-fold resistance to bisultap and also had cross-resistance to nereistoxin (monosultap, thiocyclam, and cartap), chlorpyrifos, dimethoate, and malathion but no cross-resistance to buprofezin, imidacloprid, and fipronil. To find out the biochemical mechanism of resistance to bisultap, biochemical assay was done. The results showed that cytochrome P450 monooxygenases (P450) activity in R strain was 2.71-fold that in susceptible strain (S strain), in which the changed activity for general esterase (EST) was 1.91 and for glutathione S-transferases only 1.32. Piperonyl butoxide (PBO) could significantly inhibit P450 activity (percentage of inhibition [PI]: 37.31%) in the R strain, with ESTs PI = 16.04% by triphenyl phosphate (TPP). The results also demonstrated that diethyl maleate had no synergism with bisultap. However, PBO displayed significant synergism in three different strains, and the synergism increased with resistance (S strain 1.42, Lab strain, 2.24 and R strain, 3.23). TPP also showed synergism for three strains, especially in R strain (synergistic ratio = 2.47). An in vitro biochemical study and in vivo synergistic study indicated that P450 might be play important role in the biochemical mechanism of bisultap resistance and that esterase might be the important factor of bisultap resistance. Acetylcholinesterase (AChE) insensitivity play important role in bisultap resistance. We suggest that buprofezin, imidacloprid, and fipronil could be used in resistance management programs for N. lugens via alternation and rotation with bisultap.

  20. Mechanisms and consequences of bacterial resistance to antimicrobial peptides.

    Science.gov (United States)

    Andersson, D I; Hughes, D; Kubicek-Sutherland, J Z

    2016-05-01

    Cationic antimicrobial peptides (AMPs) are an intrinsic part of the human innate immune system. Over 100 different human AMPs are known to exhibit broad-spectrum antibacterial activity. Because of the increased frequency of resistance to conventional antibiotics there is an interest in developing AMPs as an alternative antibacterial therapy. Several cationic peptides that are derivatives of AMPs from the human innate immune system are currently in clinical development. There are also ongoing clinical studies aimed at modulating the expression of AMPs to boost the human innate immune response. In this review we discuss the potential problems associated with these therapeutic approaches. There is considerable experimental data describing mechanisms by which bacteria can develop resistance to AMPs. As for any type of drug resistance, the rate by which AMP resistance would emerge and spread in a population of bacteria in a natural setting will be determined by a complex interplay of several different factors, including the mutation supply rate, the fitness of the resistant mutant at different AMP concentrations, and the strength of the selective pressure. Several studies have already shown that AMP-resistant bacterial mutants display broad cross-resistance to a variety of AMPs with different structures and modes of action. Therefore, routine clinical administration of AMPs to treat bacterial infections may select for resistant bacterial pathogens capable of better evading the innate immune system. The ramifications of therapeutic levels of exposure on the development of AMP resistance and bacterial pathogenesis are not yet understood. This is something that needs to be carefully studied and monitored if AMPs are used in clinical settings. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Mechanisms of antifungal drug resistance in Candida dubliniensis.

    LENUS (Irish Health Repository)

    Coleman, David C

    2010-06-01

    Candida dubliniensis was first described in 1995 and is the most closely related species to the predominant human fungal pathogen Candida albicans. C. dubliniensis is significantly less prevalent and less pathogenic than C. albicans and is primarily associated with infections in HIV-infected individuals and other immunocompromised cohorts. The population structure of C. dubliniensis consists of three well-defined major clades and is significantly less diverse than C. albicans. The majority of C. dubliniensis isolates are susceptible to antifungal drugs commonly used to treat Candida infections. To date only two major patterns of antifungal drug resistance have been identified and the molecular mechanisms of these are very similar to the resistance mechanisms that have been described previously in C. albicans. However, significant differences are evident in the predominant antifungal drug mechanisms employed by C. dubliniensis, differences that reflect its more clonal nature, its lower prevalence and characteristics of its genome, the complete sequence of which has only recently been determined.

  2. Characterisation of Dynamic Mechanical Properties of Resistance Welding Machines

    DEFF Research Database (Denmark)

    Wu, Pei; Zhang, Wenqi; Bay, Niels

    2005-01-01

    characterizing the dynamic mechanical characteristics of resistance welding machines is suggested, and a test set-up is designed determining the basic, independent machine parameters required in the model. The model is verified by performing a series of mechanical tests as well as real projection welds.......The dynamic mechanical properties of a resistance welding machine have significant influence on weld quality, which must be considered when simulating the welding process numerically. However, due to the complexity of the machine structure and the mutual coupling of components of the machine system......, it is very difficult to measure or calculate the basic, independent machine parameters required in a mathematical model of the machine dynamics, and no test method has so far been presented in literature, which can be applied directly in an industrial environment. In this paper, a mathematical model...

  3. Mechanisms of resistance to antimicrobial peptides in staphylococci.

    Science.gov (United States)

    Joo, Hwang-Soo; Otto, Michael

    2015-11-01

    Staphylococci are commensal bacteria living on the epithelial surfaces of humans and other mammals. Many staphylococci, including the dangerous pathogen Staphylococcus aureus, can cause severe disease when they breach the epithelial barrier. Both during their commensal life and during infection, staphylococci need to evade mechanisms of innate host defense, of which antimicrobial peptides (AMPs) play a key role in particular on the skin. Mechanisms that staphylococci have developed to evade the bactericidal activity of AMPs are manifold, comprising repulsion of AMPs via alteration of cell wall and membrane surface charges, proteolytic inactivation, sequestration, and secretion. Furthermore, many staphylococci form biofilms, which represents an additional way of protection from antimicrobial agents, including AMPs. Finally, staphylococci can sense the presence of AMPs by sensor/regulator systems that control many of those resistance mechanisms. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides. Published by Elsevier B.V.

  4. The Current State of Macrolide Resistance in Campylobacter spp.: Trends and Impacts of Resistance Mechanisms.

    Science.gov (United States)

    Bolinger, Hannah; Kathariou, Sophia

    2017-06-15

    Campylobacter spp., especially Campylobacter jejuni and C. coli , are leading bacterial foodborne pathogens worldwide. In the United States, an estimated 0.8 million cases of campylobacteriosis occur annually, mostly involving C. jejuni Campylobacteriosis is generally self-limiting, but in severe cases, treatment with antibiotics may be mandated. The increasing incidence of fluoroquinolone resistance in Campylobacter has rendered macrolides such as erythromycin and azithromycin the drugs of choice for human campylobacteriosis. The prevalence of macrolide resistance in C. jejuni remains low, but macrolide resistance can be common in C. coli Substitutions in the 23S rRNA gene, specifically A2075G, and less frequently A2074C/G, remain the most common mechanism for high-level resistance to macrolides. In C. jejuni , resistance mediated by such substitutions is accompanied by a reduced ability to colonize chickens and other fitness costs, potentially contributing to the low incidence of macrolide resistance. Interestingly, similar fitness impacts have not been noted in C. coli Also noteworthy is a novel mechanism first reported in 2014 for a C. coli isolate from China and mediated by erm (B) harbored on multidrug resistance genomic islands. The incidence of erm (B) appears to reflect clonal expansion of certain strains, and whole-genome sequencing has been critical to the elucidation of erm (B)-associated macrolide resistance in Campylobacter spp. With the exception of one report from Spain, erm (B)-mediated macrolide resistance has been restricted to Campylobacter spp., mostly C. coli , of animal and human origin from China. If erm (B)-mediated macrolide resistance does not confer fitness costs in C. jejuni , the range of this gene may expand in C. jejuni , threatening to compromise treatment effectiveness for severe campylobacteriosis cases. Copyright © 2017 American Society for Microbiology.

  5. Emergence of azole resistance in Aspergillus fumigatus and spread of a single resistance mechanism.

    Directory of Open Access Journals (Sweden)

    Eveline Snelders

    2008-11-01

    Full Text Available BACKGROUND: Resistance to triazoles was recently reported in Aspergillus fumigatus isolates cultured from patients with invasive aspergillosis. The prevalence of azole resistance in A. fumigatus is unknown. We investigated the prevalence and spread of azole resistance using our culture collection that contained A. fumigatus isolates collected between 1994 and 2007. METHODS AND FINDINGS: We investigated the prevalence of itraconazole (ITZ resistance in 1,912 clinical A. fumigatus isolates collected from 1,219 patients in our University Medical Centre over a 14-y period. The spread of resistance was investigated by analyzing 147 A. fumigatus isolates from 101 patients, from 28 other medical centres in The Netherlands and 317 isolates from six other countries. The isolates were characterized using phenotypic and molecular methods. The electronic patient files were used to determine the underlying conditions of the patients and the presence of invasive aspergillosis. ITZ-resistant isolates were found in 32 of 1,219 patients. All cases were observed after 1999 with an annual prevalence of 1.7% to 6%. The ITZ-resistant isolates also showed elevated minimum inhibitory concentrations of voriconazole, ravuconazole, and posaconazole. A substitution of leucine 98 for histidine in the cyp51A gene, together with two copies of a 34-bp sequence in tandem in the gene promoter (TR/L98H, was found to be the dominant resistance mechanism. Microsatellite analysis indicated that the ITZ-resistant isolates were genetically distinct but clustered. The ITZ-sensitive isolates were not more likely to be responsible for invasive aspergillosis than the ITZ-resistant isolates. ITZ resistance was found in isolates from 13 patients (12.8% from nine other medical centres in The Netherlands, of which 69% harboured the TR/L98H substitution, and in six isolates originating from four other countries. CONCLUSIONS: Azole resistance has emerged in A. fumigatus and might be more

  6. [Mechanisms underlying glucocorticoid resistance in chronic rhinosinusitis with nasal polyps].

    Science.gov (United States)

    Zhang, Y Y; Lou, H F; Wang, C S; Zhang, L

    2018-02-07

    Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease that occurs in the nasal and sinus mucosa, which is a common disease in otorhinolaryngology. At present, CRSwNP can be effectively treated by glucocorticoids (GC). GC binds to GC receptors in the nasal mucosa, affects the expression of inflammatory genes, inhibits the activation and action of eosinophils, T cell-associated inflammatory responses in nasal polyps, as well as tissue remodeling. However, there are some patients fall reponse to GC, so called GC resistance. The study suggests that the possible mechanism of CRSwNP GC resistance is mainly related to GC receptor abnormal, the role of cytokines and transcription factors, such as Th cells and IL-8. In addition, MAPK-related kinases and histone deacetylase in the GC signaling pathway also play important roles in the GC resistance process. This paper reviews the mechanism of GC treatment of CRSwNP, the mechanism of GC resistance and alternative treatment of GC.

  7. Dissemination and Mechanism for the MCR-1 Colistin Resistance.

    Directory of Open Access Journals (Sweden)

    Rongsui Gao

    2016-11-01

    Full Text Available Polymyxins are the last line of defense against lethal infections caused by multidrug resistant Gram-negative pathogens. Very recently, the use of polymyxins has been greatly challenged by the emergence of the plasmid-borne mobile colistin resistance gene (mcr-1. However, the mechanistic aspects of the MCR-1 colistin resistance are still poorly understood. Here we report the comparative genomics of two new mcr-1-harbouring plasmids isolated from the human gut microbiota, highlighting the diversity in plasmid transfer of the mcr-1 gene. Further genetic dissection delineated that both the trans-membrane region and a substrate-binding motif are required for the MCR-1-mediated colistin resistance. The soluble form of the membrane protein MCR-1 was successfully prepared and verified. Phylogenetic analyses revealed that MCR-1 is highly homologous to its counterpart PEA lipid A transferase in Paenibacili, a known producer of polymyxins. The fact that the plasmid-borne MCR-1 is placed in a subclade neighboring the chromosome-encoded colistin-resistant Neisseria LptA (EptA potentially implies parallel evolutionary paths for the two genes. In conclusion, our finding provids a first glimpse of mechanism for the MCR-1-mediated colistin resistance.

  8. Molecular mechanisms of cisplatin resistance in cervical cancer

    Science.gov (United States)

    Zhu, Haiyan; Luo, Hui; Zhang, Wenwen; Shen, Zhaojun; Hu, Xiaoli; Zhu, Xueqiong

    2016-01-01

    Patients with advanced or recurrent cervical cancer have poor prognosis, and their 1-year survival is only 10%–20%. Chemotherapy is considered as the standard treatment for patients with advanced or recurrent cervical cancer, and cisplatin appears to treat the disease effectively. However, resistance to cisplatin may develop, thus substantially compromising the efficacy of cisplatin to treat advanced or recurrent cervical cancer. In this article, we systematically review the recent literature and summarize the recent advances in our understanding of the molecular mechanisms underlying cisplatin resistance in cervical cancer. PMID:27354763

  9. Quinolone Resistance Mechanisms Among Salmonella enterica in Malaysia.

    Science.gov (United States)

    Thong, Kwai Lin; Ngoi, Soo Tein; Chai, Lay Ching; Teh, Cindy Shuan Ju

    2016-06-01

    The prevalence of quinolone-resistant Salmonella enterica is on the rise worldwide. Salmonella enterica is one of the major foodborne pathogens in Malaysia. Therefore, we aim to investigate the occurrence and mechanisms of quinolone resistance among Salmonella strains isolated in Malaysia. A total of 283 Salmonella strains isolated from food, humans, and animals were studied. The disk diffusion method was used to examine the quinolone susceptibility of the strains, and the minimum inhibitory concentration (MIC) values of nalidixic acid and ciprofloxacin were also determined. DNA sequencing of the quinolone resistance-determining regions (QRDRs) of gyrase and topoisomerase IV genes and the plasmid-borne qnr genes was performed. The transfer of the qnr gene was examined through transconjugation experiment. A total of 101 nalidixic acid-resistant Salmonella strains were identified. In general, all strains were highly resistant to nalidixic acid (average MICNAL, 170 μg/ml). Resistance to ciprofloxacin was observed in 30.7% of the strains (1 ≤ MICCIP ≤ 2 μg/ml). Majority of the strains contained missense mutations in the QRDR of gyrA (69.3%). Silent mutations were frequently detected in gyrB (75.2%), parC (27.7%), and parE (51.5%) within and beyond the QRDRs. Novel mutations were detected in parC and parE. The plasmid-borne qnrS1 variant was found in 36.6% of the strains, and two strains were found to be able to transfer the qnrS1 gene. Overall, mutations in gyrA and the presence of qnrS1 genes might have contributed to the high level of quinolone resistance among the strains. Our study provided a better understanding on the status of quinolone resistance among Salmonella strains circulating in Malaysia.

  10. Mechanisms and evolution of plant resistance to aphids.

    Science.gov (United States)

    Züst, Tobias; Agrawal, Anurag A

    2016-01-06

    Aphids are important herbivores of both wild and cultivated plants. Plants rely on unique mechanisms of recognition, signalling and defence to cope with the specialized mode of phloem feeding by aphids. Aspects of the molecular mechanisms underlying aphid-plant interactions are beginning to be understood. Recent advances include the identification of aphid salivary proteins involved in host plant manipulation, and plant receptors involved in aphid recognition. However, a complete picture of aphid-plant interactions requires consideration of the ecological outcome of these mechanisms in nature, and the evolutionary processes that shaped them. Here we identify general patterns of resistance, with a special focus on recognition, phytohormonal signalling, secondary metabolites and induction of plant resistance. We discuss how host specialization can enable aphids to co-opt both the phytohormonal responses and defensive compounds of plants for their own benefit at a local scale. In response, systemically induced resistance in plants is common and often involves targeted responses to specific aphid species or even genotypes. As co-evolutionary adaptation between plants and aphids is ongoing, the stealthy nature of aphid feeding makes both the mechanisms and outcomes of these interactions highly distinct from those of other herbivore-plant interactions.

  11. Dynamic encapsulation of hydrophilic nisin in hydrophobic poly (lactic acid) particles with controlled morphology by a single emulsion process.

    Science.gov (United States)

    Ji, Shaowen; Lu, Jue; Liu, Zhiguo; Srivastava, Devesh; Song, Anna; Liu, Yan; Lee, Ilsoon

    2014-06-01

    Hydrophilic nisin-loaded hydrophobic poly (lactic acid) (PLA) particles with controlled size and shape were successfully produced utilizing a one-step single emulsification method. Preliminary shear stress and temperature tests showed that there was no significant loss in the nisin inhibition activity during this process. PLA/nisin composite particles were prepared into solid nanocomposite spheres (50-200 nm) or hollow microcomposite spheres (1-5 μm) under the operative conditions developed in our previous study, in which the hydrophilic nisin in the aqueous phase solution could be entrapped in the hydrophobic polymer in the emulsification process generating either single or multiple emulsions. The incorporation of nisin in PLA had little effect on key processing conditions, which allows the dynamic control of the morphology and property of resulting particles. Microscopic and surface analyses suggested that nisin was dispersed uniformly inside the polymer matrix and adsorbed on the particle surface. The encapsulation amount and efficiency were enhanced with the increase in nisin loading in the aqueous solution. Unique reversible control of particle size and shape by this process was successfully applied in the nisin encapsulation. Alternating temperature in the repeating emulsification steps improved the encapsulation efficiency while generated particles in desired size and shape. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Controlled Gene Expression Systems for Lactic Acid Bacteria : Transferable Nisin-Inducible Expression Cassettes for Lactococcus, Leuconostoc, and Lactobacillus spp.

    NARCIS (Netherlands)

    Kleerebezem, Michiel; Beerthuyzen, Marke M.; Vaughan, Elaine E.; Vos, Willem M. de; Kuipers, Oscar P.

    1997-01-01

    A transferable dual-plasmid inducible gene expression system for use in lactic acid bacteria that is based on the autoregulatory properties of the antimicrobial peptide nisin produced by Lactococcus lactis was developed. Introduction of the two plasmids allowed nisin-inducible gene expression in

  13. Semisynthetic Lipopeptides Derived from Nisin Display Antibacterial Activity and Lipid II Binding on Par with That of the Parent Compound

    NARCIS (Netherlands)

    Koopmans, Timo; Wood, Thomas M.; 't Hart, Peter; Kleijn, Laurens H. J.; Hendrickx, Antoni P. A.; Willems, Rob J. L.; Breukink, Eefjan; Martin, Nathaniel I.

    2015-01-01

    The lipid II-binding N-terminus of nisin, comprising the so-called A/B ring system, was synthetically modified to provide antibacterially active and proteolytically stable derivatives. A variety of lipids were coupled to the C-terminus of the nisin A/B ring system to generate semisynthetic

  14. Mechanisms and improvement of acid resistance in lactic acid bacteria.

    Science.gov (United States)

    Wang, Chao; Cui, Yanhua; Qu, Xiaojun

    2018-03-01

    Lactic acid bacteria (LAB) can take advantage of fermentable carbohydrates to produce lactic acid. They are proverbially applied in industry, agricultural production, animal husbandry, food enterprise, pharmaceutical engineering and some other important fields, which are closely related to human life. For performing the probiotic functions, LAB have to face the low pH environment of the gastrointestinal tract. Therefore, acid resistance of LAB is of great importance not only for their own growth, but also for fermentation and preparation of probiotic products. Recent research studies on acid resistance mechanisms of LAB are mainly focused on neutralization process, biofilm and cell density, proton pump, protection of macromolecules, pre-adaptation and cross-protection, and effect of solutes. In this context, biotechnological strategies such as synthetic biology, genome shuffling, high pressure homogenization and adaptive laboratory evolution were also used to improve the acid resistance of LAB to respond to constantly changing low pH environment.

  15. Combined effects of heat, nisin and acidification on the inactivation of Clostridium sporogenes spores in carrot-alginate particles: from kinetics to process validation.

    Science.gov (United States)

    Naim, F; Zareifard, M R; Zhu, S; Huizing, R H; Grabowski, S; Marcotte, M

    2008-10-01

    Combined effects of mild temperatures, acidification and nisin on the thermal resistance of Clostridium sporogenes ATCC 11437 spores were assessed. Inoculated carrot-alginate particles were used as a solid-food model for the validation of the spore inactivation during the flow of a solid-liquid food system through the holding tube of an aseptic processing unit. Inactivation kinetics was studied in a water bath with the spores inoculated into carrot-alginate particles and in Sorensen's phosphate buffer. For temperatures of 70-90 degrees C, D-values in the buffer were 24.9-5.7 min, much lower than those evaluated for the particles (115.1-22.2 min). Statistical analyses showed significant synergistic effects of temperature and pH on spore inactivation for both media. Acidification reduced the heat resistance of the spores by reducing the D-values. Nisin was not significantly effective at the lower concentrations (up to 750 IU/g). The combination of 90 degrees C, pH: 4.5 and 500IU/g nisin resulted in a ten-fold decrease of the D-value for spores inoculated in the particles (from 111.1 to 10.6 min). Microbial validation tests were conducted using a pilot-scale aseptic processing unit with a mixture of carrot cubes (10%) and carrier liquid of 2%-carboxymethylcellulose solution (90%). Spore-inoculated carrot-alginate particles (initial counts of 106 CFU/g, obtained after come-up-time pre-heat) with pH 3.5 and 2000 IU/g nisin were processed at 90 degrees C in the aseptic processing unit. Microbial analysis showed no spore survivors in the particles after passing through the holding tube (5.2-6.0 min of residence time). The proposed combination of these hurdles significantly enhanced the spore inactivation rate (D(90)=1.17 min) as compared to that for thermal treatment only (D(90)=19.6 min).

  16. Mechanisms of resistance to daptomycin in Staphylococcus aureus.

    Science.gov (United States)

    Gómez Casanova, N; Siller Ruiz, M; Muñoz Bellido, J L

    2017-12-01

    Daptomycin is a cyclic lipopeptide active against multidrug-resistant Gram-positives, including methicillin-resistant Staphylococcus aureus (MRSA) and S. aureus with reduced susceptibility to vancomycin. It is 4-8 fold as active as vancomycin against methicillin-susceptible S. aureus (MSSA) and MRSA, and retains most of this activity against S. aureus with reduced susceptibility to vancomycin. The mechanism of action of daptomycin is not fully understood. Daptomycin binds to the bacterial cytoplasmic membrane, leading to depolarization due to the loss of potassium ions from the cytoplasm. Daptomycin non-susceptibility is unusual in the clinical setting. Different mechanisms have been proposed to explain daptomycin-resistance, most of them associated to changes in composition, charge and fluidity of the cell wall. The mprF mutations, which lead to an increase in the lysyl-phosphatidyl glycerol production, and rpoB and rpoC mutations (rpo genes encode for bacterial RNA polymerase subunits) have been proposed as associated to daptomycin-resistance, but a number of mutations in other genes ( walK, cls, ggrA…) have been proposed.

  17. Degradation of sulfonamides as a microbial resistance mechanism.

    Science.gov (United States)

    Vila-Costa, Maria; Gioia, Rosalinda; Aceña, Jaume; Pérez, Sandra; Casamayor, Emilio O; Dachs, Jordi

    2017-05-15

    Two of the main mechanisms of bacterial resistance to sulfonamides in aquatic systems, spread of antibiotic resistance genes (ARG) among the microbial community and in-situ bacterial sulfonamide degradation, were studied in mesocosms experiments using water and cobble biofilms from upstream (pristine waters) and downstream (polluted waters) from the Llobregat river, NE Iberian Peninsula. Mesocosms were prepared at two different concentrations (5000 ng/L and 1000 ng/L) of sulfonamides antibiotics (sulfamethazine and sulfamethoxazole). Concentrations of ARG, nutrients, sulfonamides and their degradation products were measured during the time course of the experiments. Sulfonamides were efficiently degraded by the biofilms during the first four weeks of the experiment. The abundance of ARG in biofilms sharply decreased after addition of high concentrations of sulfonamides, but this was not observed in the mesocosms treated with low concentrations of sulfonamides. Sulfonamide degradation was faster in polluted waters and at high concentrations of sulfonamide (and lower ARG abundances), suggesting that both degradation and ARG are two complementary resistance strategies employed by the microbial community. This study shows that microbial degradation of antibiotics is an efficient resistance mechanism coupled with the presence of ARG, and suggests that in situ degradation prevails at high concentrations of antibiotics whereas physiological adaptation by ARG spread would be more important under relatively lower concentrations of antibiotics. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Molecular Mechanisms of Intrinsic Streptomycin Resistance in Mycobacterium abscessus.

    Science.gov (United States)

    Dal Molin, Michael; Gut, Myriam; Rominski, Anna; Haldimann, Klara; Becker, Katja; Sander, Peter

    2018-01-01

    Streptomycin, the first drug used for the treatment of tuberculosis, shows limited activity against the highly resistant pathogen Mycobacterium abscessus We recently identified two aminoglycoside-acetylating genes [ aac(2') and eis2 ] which, however, do not affect susceptibility to streptomycin. This suggests the existence of a discrete mechanism of streptomycin resistance. M. abscessus BLASTP analysis identified MAB_2385 as a close homologue of the 3″- O -phosphotransferase [APH(3″)] from the opportunistic pathogen Mycobacterium fortuitum as a putative streptomycin resistance determinant. Heterologous expression of MAB_2385 in Mycobacterium smegmatis increased the streptomycin MIC, while the gene deletion mutant M. abscessus ΔMAB_2385 showed increased streptomycin susceptibility. The MICs of other aminoglycosides were not altered in M. abscessus ΔMAB_2385. This demonstrates that MAB_2385 encodes a specific and prime innate streptomycin resistance determinant in M. abscessus We further explored the feasibility of applying rpsL -based streptomycin counterselection to generate gene deletion mutants in M. abscessus Spontaneous streptomycin-resistant mutants of M. abscessus ΔMAB_2385 were selected, and we demonstrated that the wild-type rpsL is dominant over the mutated rpsL K43R in merodiploid strains. In a proof of concept study, we exploited this phenotype for construction of a targeted deletion mutant, thereby establishing an rpsL -based counterselection method in M. abscessus . Copyright © 2017 American Society for Microbiology.

  19. Molecular epidemiological survey of bacteremia by multidrug resistant Pseudomonas aeruginosa: the relevance of intrinsic resistance mechanisms.

    Directory of Open Access Journals (Sweden)

    Raquel Cristina Cavalcanti Dantas

    Full Text Available The bacterial factors associated with bacteremia by multidrug-resistant and extensively drug-resistant P. aeruginosa, including overexpression of efflux pumps, AmpC overproduction, and loss/alteration of the OprD porin in isolates that are non-Metallo-β-Lactamase producing were analyzed in a retrospective study. Molecular analyses included strain typing by Pulsed Field Gel Electrophoresis and identification of key genes via qualitative and quantitative PCR-based assays. Previous use of carbapenems and tracheostomy was independently associated with the development of bacteremia by extensively drug-resistant and multidrug-resistant strains of P. aeruginosa. A high consumption of antimicrobials was observed, and 75.0% of the isolates contained amplicons with the blaSPM-1 and blaVIM genes. Of the 47 non-Metallo-β-Lactamase isolates, none had another type of carbapenemase. However, the isolates exhibited high rates of hyperproduction of AmpC, loss of the OprD porin (71.4% and the presence of MexABOprM (57.1% and MexXY (64.3%. This study suggests that in non-Metallo-β-Lactamase isolates, the association of intrinsic resistance mechanisms could contributes to the expression of multidrug-resistant/extensively drug-resistant phenotypes.

  20. [Molecular characterization of resistance mechanisms: methicillin resistance Staphylococcus aureus, extended spectrum β-lactamases and carbapenemases].

    Science.gov (United States)

    Oteo, Jesús; Belén Aracil, María

    2015-07-01

    Multi-drug resistance in bacterial pathogens increases morbidity and mortality in infected patients and it is a threat to public health concern by their high capacity to spread. For both reasons, the rapid detection of multi-drug resistant bacteria is critical. Standard microbiological procedures require 48-72 h to provide the antimicrobial susceptibility results, thus there is emerging interest in the development of rapid detection techniques. In recent years, the use of selective and differential culture-based methods has widely spread. However, the capacity for detecting antibiotic resistance genes and their low turnaround times has made molecular methods a reference for diagnosis of multidrug resistance. This review focusses on the molecular methods for detecting some mechanisms of antibiotic resistance with a high clinical and epidemiological impact: a) Enzymatic resistance to broad spectrum β-lactam antibiotics in Enterobacteriaceae, mainly extended spectrum β-lactamases (ESBL) and carbapenemases; and b) methicillin resistance in Staphylococcus aureus. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  1. Fluoroquinolone resistance mechanisms in multidrug-resistant Escherichia coli isolated from extraintestinal infections in dogs.

    Science.gov (United States)

    Gibson, Justine S; Cobbold, Rowland N; Kyaw-Tanner, Myat T; Heisig, Peter; Trott, Darren J

    2010-11-20

    Fluoroquinolone resistance is an emerging problem in companion animal practice. The present study aimed to determine comparative fluoroquinolone minimum inhibitory concentrations (MICs) for enrofloxacin, marbofloxacin and pradofloxacin and identify plasmid-mediated quinolone resistance (PMQR) mechanisms in 41 multidrug-resistant (MDR) Escherichia coli isolates representing three main clonal groups (CGs) cultured from extraintestinal infections in dogs. All isolates were resistant to fluoroquinolones and the PMQR genes qnrA1, qnrB2, qnrS1 and qepA were identified in isolates from each CG. For a subset of 13 representative isolates, fluoroquinolone chromosomal resistance mechanisms were characterized. CG1 isolates had three mutations in the quinolone resistance determining region (QRDR), two in gyrA (Ser TCG-83→Leu TTG and Asp GAC-87→Asn AAC) and one in parC (Ser AGC-80→Ile ATT), whilst CG2 and CG3 isolates also possessed an additional mutation in parC (Glu GAA-84→Gly GGA) which was reflected in higher fluoroquinolone MICs compared to CG1. Organic solvent tolerance was demonstrated in 8 of the 13 isolates, and all 13 isolates demonstrated enhanced efflux on the basis of a 4-fold decrease or greater in the MIC of enrofloxacin when incubated with an efflux pump inhibitor. A mutation in acrR which can cause overexpression of the AcrAB multidrug efflux pump was detected in CG1 strains. These findings indicate that fluoroquinolone resistance in MDR E. coli isolated from extraintestinal infections in dogs is associated with a combination of target mutations in the QRDRs, transferable PMQR mechanisms and enhanced efflux. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Towards the Understanding of Resistance Mechanisms in Clinically Isolated Trimethoprim-resistant, Methicillin-resistant Staphylococcus aureus Dihydrofolate Reductase

    Energy Technology Data Exchange (ETDEWEB)

    Frey, K.; Lombardo, M; Wright, D; Anderson, A

    2010-01-01

    Resistance to therapeutics such as trimethoprim-sulfamethoxazole has become an increasing problem in strains of methicillin-resistant Staphylococcus aureus (MRSA). Clinically isolated trimethoprim-resistant strains reveal a double mutation, H30N/F98Y, in dihydrofolate reductase (DHFR). In order to develop novel and effective therapeutics against these resistant strains, we evaluated a series of propargyl-linked antifolate lead compounds for inhibition of the mutant enzyme. For the propargyl-linked antifolates, the F98Y mutation generates minimal (between 1.2- and 6-fold) losses of affinity and the H30N mutation generates greater losses (between 2.4- and 48-fold). Conversely, trimethoprim affinity is largely diminished by the F98Y mutation (36-fold) and is not affected by the H30N mutation. In order to elucidate a mechanism of resistance, we determined a crystal structure of a complex of this double mutant with a lead propargyl-linked antifolate. This structure suggests a resistance mechanism consistent both for the propargyl-linked class of antifolates and for trimethoprim that is based on the loss of a conserved water-mediated hydrogen bond.

  3. [Mechanisms of microorganism resistance to beta-lactam antibiotics].

    Science.gov (United States)

    D'iachkova, V S; Bazhukova, T A

    2014-01-01

    Literature data on molecular mechanisms of resistance to beta-lactam antibiotics have been summarized. The following mechanisms are examined: appearance ofpenicillin-binding proteins (PBP) with lower affinity to beta-lactam antibiotics; production by microorganisms of enzymes (beta-lactamases) that hydrolyze beta-lactam ring; disruption of microbial cell outer membrane permeability and active secretion of antibiotics from the microbial cell (effiux-effect). Characterization of extended spectrum beta-lactamases (ESBL) as well as data on structure of SCCmec element of MRSA and bacterial efflux system (RND) is presented.

  4. Embryo mechanics: balancing force production with elastic resistance during morphogenesis.

    Science.gov (United States)

    Davidson, Lance A

    2011-01-01

    Morphogenesis requires the spatial and temporal control of embryo mechanics, including force production and mechanical resistance to those forces, to coordinate tissue deformation and large-scale movements. Thus, biomechanical processes play a key role in directly shaping the embryo. Additional roles for embryo mechanics during development may include the patterning of positional information and to provide feedback to ensure the success of morphogenetic movements in shaping the larval body and organs. To understand the multiple roles of mechanics during development requires familiarity with engineering principles of the mechanics of structures, the viscoelastic properties of biomaterials, and the integration of force and stress within embryonic structures as morphogenesis progresses. In this chapter, we review the basic engineering principles of biomechanics as they relate to morphogenesis, introduce methods for quantifying embryo mechanics and the limitations of these methods, and outline a formalism for investigating the role of embryo mechanics in birth defects. We encourage the nascent field of embryo mechanics to adopt standard engineering terms and test methods so that studies of diverse organisms can be compared and universal biomechanical principles can be revealed. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. An insight into the drug resistance profile & mechanism of drug resistance in Neisseria gonorrhoeae.

    Science.gov (United States)

    Patel, Achchhe Lal; Chaudhry, Uma; Sachdev, Divya; Sachdeva, Poonam Nagpal; Bala, Manju; Saluja, Daman

    2011-10-01

    Among the aetiological agents of treatable sexually transmitted diseases (STDs), Neissseria gonorrhoeae is considered to be most important because of emerging antibiotic resistant strains that compromise the effectiveness of treatment of the disease - gonorrhoea. In most of the developing countries, treatment of gonorrhoea relies mainly on syndromic management rather than the aetiological based therapy. Gonococcal infections are usually treated with single-dose therapy with an agent found to cure > 95 per cent of cases. Unfortunately during the last few decades, N. gonorrhoeae has developed resistance not only to less expensive antimicrobials such as sulphonamides, penicillin and tetracyclines but also to fluoroquinolones. The resistance trend of N. gonorrhoeae towards these antimicrobials can be categorised into pre-quinolone, quinolone and post-quinolone era. Among the antimicrobials available so far, only the third-generation cephalosporins could be safely recommended as first-line therapy for gonorrhoea globally. However, resistance to oral third-generation cephalosporins has also started emerging in some countries. Therefore, it has become imperative to initiate sustained national and international efforts to reduce infection and misuse of antibiotics so as to prevent further emergence and spread of antimicrobial resistance. It is necessary not only to monitor drug resistance and optimise treatment regimens, but also to gain insight into how gonococcus develops drug resistance. Knowledge of mechanism of resistance would help us to devise methods to prevent the occurrence of drug resistance against existing and new drugs. Such studies could also help in finding out new drug targets in N. gonorrhoeae and also a possibility of identification of new drugs for treating gonorrhoea.

  6. Ciprofloxacin-resistant Escherichia coli in Central Greece: mechanisms of resistance and molecular identification

    Directory of Open Access Journals (Sweden)

    Mavroidi Angeliki

    2012-12-01

    Full Text Available Abstract Background Fluoroquinolone resistant E. coli isolates, that are also resistant to other classes of antibiotics, is a significant challenge to antibiotic treatment and infection control policies. In Central Greece a significant increase of ciprofloxacin-resistant Escherichia coli has occurred during 2011, indicating the need for further analysis. Methods A total of 106 ciprofloxacin-resistant out of 505 E. coli isolates consecutively collected during an eight months period in a tertiary Greek hospital of Central Greece were studied. Antimicrobial susceptibility patterns and mechanisms of resistance to quinolones were assessed, whereas selected isolates were further characterized by multilocus sequence typing and β-lactamase content. Results Sequence analysis of the quinolone-resistance determining region of the gyrA and parC genes has revealed that 63% of the ciprofloxacin-resistant E. coli harbored a distinct amino acid substitution pattern (GyrA:S83L + D87N; ParC:S80I + E84V, while 34% and 3% carried the patterns GyrA:S83L + D87N; ParC:S80I and GyrA:S83L + D87N; ParC:S80I + E84G respectively. The aac (6’-1b-cr plasmid-mediated quinolone resistance determinant was also detected; none of the isolates was found to carry the qnrA, qnrB and qnrS. Genotyping of a subset of 35 selected ciprofloxacin-resistant E. coli by multilocus sequence typing has revealed the presence of nine sequence types; ST131 and ST410 were the most prevalent and were exclusively correlated with hospital and health care associated infections, while strains belonging to STs 393, 361 and 162 were associated with community acquired infections. The GyrA:S83L + D87N; ParC:S80I + E84V substitution pattern was found exclusively among ST131 ciprofloxacin-resistant E. coli. Extended-spectrum β-lactamase-positive ST131 ciprofloxacin-resistant isolates produced CTX-M-type enzymes; eight the CTX-M-15 and one the CTX-M-3 variant. CTX-M-1 like and KPC-2 enzymes were detected

  7. Characterization of multidrug‑resistant osteosarcoma sublines and the molecular mechanisms of resistance.

    Science.gov (United States)

    Yang, Jian-Zeng; Ma, Shu-Rong; Rong, Xiao-Li; Zhu, Mei-Ju; Ji, Qiu-Ye; Meng, Ling-Jie; Gao, Yi-Yao; Yang, Yu-Dan; Wang, Yan

    2016-10-01

    Multidrug resistance (MDR) is a challenge for the treatment of cancer and the underlying molecular mechanisms remain elusive. The current study exposed MG63 osteosarcoma cells to increasing concentrations of vincristine (VCR) to establish four VCR‑resistant MG63/VCR cell sublines (MG63/VCR1, 2, 3 and 4). The drug resistance indices (RI) of these sublines was detected with the CCK‑8 assay and determined to be163, 476, 1,247, and 2,707‑fold higher than that of parental cells, respectively. These sublines also exhibited cross‑resistance to doxorubicin, paclitaxel and pirarubicin. With increased RI, the proliferative capacity of these sublines was gradually reduced and cell morphology was also altered, characterized by increased formation of pseudopodia and long cytoplasmic processes at opposite poles. However, the migration capacity and expression of certain drug resistance‑associated genes were not in accordance with the increased RI; multidrug resistance protein 1 (MDR1) expression was significantly increased in these sublines compared with parental cells. However, in the highly resistant MG63/VCR3 and MG63/VCR4 cells, MDR‑associated protein 1, topoisomerase II and LIM domain kinase 1 levels were significantly reduced compared with the moderately resistant MG63/VCR2 cells. Expression of glutathione S‑transferase‑π mRNA was determined using reverse transcription‑quantitative polymerase chain reaction and determined that it was not changed between MG63 and MG63/VCR cells. The data of the present study demonstrated that the molecular alterations of drug resistance may change with the degree of drug resistance. Taking cell morphology into consideration, the intratumor clonal and phenotypic heterogeneity may be responsible for drug resistance. These MG63/VCR sublines may be a valuable tool to assess drug resistance and the underlying mechanisms, and to identify novel drug resistance‑associated genes or strategies to overcome MDR in human

  8. Studies on Acinetobacter baumannii involving multiple mechanisms of carbapenem resistance.

    Science.gov (United States)

    Sen, B; Joshi, S G

    2016-03-01

    Characterize the genetic type and resistance mechanisms of 16 carbapenem-resistant Acinetobacter baumannii (CRAB) isolates recovered between January 2010 and March 2011 from US tertiary-care hospital. A modified Hodge test demonstrated the presence of carbapenemases, but meropenem and ethylenediaminetetraacetic acid (EDTA) double-disc synergy tests and PCR for metallo-β-lactamase (MBL) genes were negative. The genes of ampC β-lactamase and efflux pump of adeABC and adeIJK were detected. The presence of oxacillinase (OXA)-like genes, blaOXA-51-like , blaOXA-23-like and blaOXA-40-like genes, and insertion sequence ISAba1 in promoter region of blaOXA-51-like and blaOXA-23-like genes were detected; and confirmed by RT-PCR analyses. The sequencing of blaOXA-51-like genes revealed two major alleles, blaOXA-66-like (blaOXA-82 ) and blaOXA-113 from 31·2 to 68·8% of isolates respectively. The blaOXA-23 and blaOXA-72 genes showed high expression and found co-harbouring blaOXA-51-like gene preceded by ISAba-1. All CRAB isolates revealed significant reduction in carO transcription, indicated downregulation of CarO porin system, a potentially independent mechanism of carbapenam resistance. Sequencing of carO gene from representative isolates showed no ISAba1 insertional inactivation. Pulsed-field gel electrophoresis revealed a clonal relationship. CRAB exhibited diversity of mechanisms of carbapenem resistance, and clonal relationship. Studies on distinct outbreaks of CRAB are alarming situation for clinicians. © 2015 The Society for Applied Microbiology.

  9. Antimicrobial activity of nisin adsorbed to surfaces commonly used in the food industry.

    Science.gov (United States)

    Guerra, Nelson P; Araujo, Ana Belén; Barrera, Ana M; Agrasar, Ana Torrado; Macías, Cristina López; Carballo, Julia; Pastrana, Lorenzo

    2005-05-01

    The adsorption isotherms of nisin to three food contact surfaces, stainless steel, polyethyleneterephthalate (PET), and rubber at 8, 25, 40, and 60 degrees C, were calculated. For all surfaces, the increase in temperature led to a decrease in the affinity between nisin and the surface. The rubber adsorbed a higher amount of nisin (0.697 microg/cm2) in comparison with PET (0.665 microg/cm2) and stainless steel (0.396 microg/cm2). Adsorption of nisin to the stainless steel surface described L-2 type curves for all temperatures assayed. However, for PET and rubber surfaces, the isotherms were L-2 type (at 40 and 60 degrees C) and L-4 type curves (at 8 and 25 degrees C). Nisin retained its antibacterial activity once adsorbed to the food contact surfaces and was able to inhibit the growth of Enterococcus hirae CECT 279 on Rothe agar medium. The attachment of three Listeria monocytogenes strains to the three surfaces was found to be dependent on the surface, the strain, and the initial bacterial suspension in contact with the surface. The adsorption of Nisaplin on surfaces reduced the attachment of all L. monocytogenes strains tested. The effect of PET-based bioactive packaging in food was very encouraging. When applied to a food system, nisin-adsorbed PET bottles reduced significantly (P < 0.05) the levels of the total aerobic plate counts in skim milk by approximately 1.4 log units after 24 days of refrigerated storage (4 degrees C), thus extending its shelf life.

  10. Antimicrobial Resistance of Hypervirulent Klebsiella pneumoniae: Epidemiology, Hypervirulence-Associated Determinants, and Resistance Mechanisms

    Directory of Open Access Journals (Sweden)

    Chang-Ro Lee

    2017-11-01

    Full Text Available Klebsiella pneumoniae is one of the most clinically relevant species in immunocompromised individuals responsible for community-acquired and nosocomial infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Since the mid-1980s, hypervirulent K. pneumoniae, generally associated with the hypermucoviscosity phenotype, has emerged as a clinically significant pathogen responsible for serious disseminated infections, such as pyogenic liver abscesses, osteomyelitis, and endophthalmitis, in a generally younger and healthier population. Hypervirulent K. pneumoniae infections were primarily found in East Asia and now are increasingly being reported worldwide. Although most hypervirulent K. pneumoniae isolates are antibiotic-susceptible, some isolates with combined virulence and resistance, such as the carbapenem-resistant hypervirulent K. pneumoniae isolates, are increasingly being detected. The combination of multidrug resistance and enhanced virulence has the potential to cause the next clinical crisis. To better understand the basic biology of hypervirulent K. pneumoniae, this review will provide a summarization and discussion focused on epidemiology, hypervirulence-associated factors, and antibiotic resistance mechanisms of such hypervirulent strains. Epidemiological analysis of recent clinical isolates in China warns the global dissemination of hypervirulent K. pneumoniae strains with extensive antibiotic resistance in the near future. Therefore, an immediate response to recognize the global dissemination of this hypervirulent strain with resistance determinants is an urgent priority.

  11. Antimicrobial Resistance of Hypervirulent Klebsiella pneumoniae: Epidemiology, Hypervirulence-Associated Determinants, and Resistance Mechanisms

    Science.gov (United States)

    Lee, Chang-Ro; Lee, Jung Hun; Park, Kwang Seung; Jeon, Jeong Ho; Kim, Young Bae; Cha, Chang-Jun; Jeong, Byeong Chul; Lee, Sang Hee

    2017-01-01

    Klebsiella pneumoniae is one of the most clinically relevant species in immunocompromised individuals responsible for community-acquired and nosocomial infections, including pneumonias, urinary tract infections, bacteremias, and liver abscesses. Since the mid-1980s, hypervirulent K. pneumoniae, generally associated with the hypermucoviscosity phenotype, has emerged as a clinically significant pathogen responsible for serious disseminated infections, such as pyogenic liver abscesses, osteomyelitis, and endophthalmitis, in a generally younger and healthier population. Hypervirulent K. pneumoniae infections were primarily found in East Asia and now are increasingly being reported worldwide. Although most hypervirulent K. pneumoniae isolates are antibiotic-susceptible, some isolates with combined virulence and resistance, such as the carbapenem-resistant hypervirulent K. pneumoniae isolates, are increasingly being detected. The combination of multidrug resistance and enhanced virulence has the potential to cause the next clinical crisis. To better understand the basic biology of hypervirulent K. pneumoniae, this review will provide a summarization and discussion focused on epidemiology, hypervirulence-associated factors, and antibiotic resistance mechanisms of such hypervirulent strains. Epidemiological analysis of recent clinical isolates in China warns the global dissemination of hypervirulent K. pneumoniae strains with extensive antibiotic resistance in the near future. Therefore, an immediate response to recognize the global dissemination of this hypervirulent strain with resistance determinants is an urgent priority. PMID:29209595

  12. Mechanisms of Nuclear Export in Cancer and Resistance to Chemotherapy

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    Mohamed El-Tanani

    2016-03-01

    Full Text Available Tumour suppressor proteins, such as p53, BRCA1, and ABC, play key roles in preventing the development of a malignant phenotype, but those that function as transcriptional regulators need to enter the nucleus in order to function. The export of proteins between the nucleus and cytoplasm is complex. It occurs through nuclear pores and exported proteins need a nuclear export signal (NES to bind to nuclear exportin proteins, including CRM1 (Chromosomal Region Maintenance protein 1, and the energy for this process is provided by the RanGTP/RanGDP gradient. Due to the loss of DNA repair and cell cycle checkpoints, drug resistance is a major problem in cancer treatment, and often an initially successful treatment will fail due to the development of resistance. An important mechanism underlying resistance is nuclear export, and a number of strategies that can prevent nuclear export may reverse resistance. Examples include inhibitors of CRM1, antibodies to the nuclear export signal, and alteration of nuclear pore structure. Each of these are considered in this review.

  13. Mechanisms Underlying the Antidepressant Response and Treatment Resistance

    Directory of Open Access Journals (Sweden)

    Marjorie Rose Levinstein

    2014-06-01

    Full Text Available Depression is a complex and heterogeneous disorder affecting millions of Americans. There are several different medications and other treatments that are available and effective for many patients with depression. However, a substantial percentage of patients fail to achieve remission with these currently available interventions, and relapse rates are high. Therefore, it is necessary to determine both the mechanisms underlying the antidepressant response and the differences between responders and non-responders to treatment. Delineation of these mechanisms largely relies on experiments that utilize animal models. Therefore, this review provides an overview of the various mouse models that are currently used to assess the antidepressant response, such as chronic mild stress, social defeat, and chronic corticosterone. We discuss how these mouse models can be used to advance our understanding of the differences between responders and non-responders to antidepressant treatment. We also provide an overview of experimental treatment modalities that are used for treatment-resistant depression, such as deep brain stimulation and ketamine administration. We will then review the various genetic polymorphisms and transgenic mice that display resistance to antidepressant treatment. Finally, we synthesize the published data to describe a potential neural circuit underlying the antidepressant response and treatment resistance.

  14. [Ecology and mechanisms of bacterial resistance to antibiotics in peritonitis].

    Science.gov (United States)

    Edern, Anita; Fines-Guyon, Marguerite; Castrale, Cindy; Ficheux, Maxence; Ryckelynck, Jean-Philippe; Lobbedez, Thierry

    2012-11-01

    Peritonitis remains a common complication of peritoneal dialysis. The aim of our study is to describe the mechanisms of antibiotic resistance in bacteria isolated during peritonitis in peritoneal dialysis, to determine whether antibiotic therapy proposed by the International Society for Peritoneal Dialysis (ISPD) is adapted to the mechanisms of resistance. All causative microorganisms of peritonitis, isolated in 106 dialysis patients and reported 170 episodes of peritonitis, during the study period (01/01/2005 to 31/12/2010) were reviewed. According to the usual classification, twelve groups of microorganism were created. An interpretive reading of antibiograms was performed in each group to identify resistance phenotypes. The species most frequently isolated are coagulase-negative staphylococci (n=73) of which 46 had PBP2a (penicillin-binding protein). Many Enterobacteriaceae were also isolated (n=45), they are susceptible to third generation cephalosporins with the exception of Enterobacteriaceae producing an extended spectrum β-lactamase (ESBL) or a cephalosporinase. Except for staphylococci, probabilistic antibiotic therapy recommended by the ISPD to treat peritonitis is effective. Indeed, many staphylococci producing a PBP2a, a first-generation cephalosporin cannot be administered in all cases. It is therefore necessary to identify patients with a strain of staphylococcus producing a PBP2a, it must be treated by vancomycin. Copyright © 2012 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  15. On the mechanism of chloroquine resistance in Plasmodium falciparum.

    KAUST Repository

    Chinappi, Mauro

    2010-11-19

    Resistance to chloroquine of malaria strains is known to be associated with a parasite protein named PfCRT, the mutated form of which is able to reduce chloroquine accumulation in the digestive vacuole of the pathogen. Whether the protein mediates extrusion of the drug acting as a channel or as a carrier and which is the protonation state of its chloroquine substrate is the subject of a scientific debate. We present here an analytical approach that explores which combination of hypotheses on the mechanism of transport and the protonation state of chloroquine are consistent with available equilibrium experimental data. We show that the available experimental data are not, by themselves, sufficient to conclude whether the protein acts as a channel or as a transporter, which explains the origin of their different interpretation by different authors. Interestingly, though, each of the two models is only consistent with a subset of hypotheses on the protonation state of the transported molecule. The combination of these results with a sequence and structure analysis of PfCRT, which strongly suggests that the molecule is a carrier, indicates that the transported species is either or both the mono and di-protonated forms of chloroquine. We believe that our results, besides shedding light on the mechanism of chloroquine resistance in P. falciparum, have implications for the development of novel therapies against resistant malaria strains and demonstrate the usefulness of an approach combining systems biology strategies with structural bioinformatics and experimental data.

  16. Molecular mechanism of free fatty acids-induced insulin resistance

    Directory of Open Access Journals (Sweden)

    Hui-zhe CAO

    2017-02-01

    Full Text Available Insulin resistance (IR is a complex metabolic disorder related to several diseases including type 2 diabetes (T2DM, hypertension and dyslipidemia. These diseases are all independent risk factors for cardiovascular disease. Lipid metabolism disorder has toxic effects on cells and may cause or aggravate IR in performance of elevated plasma levels of triglyceride (TG and free fatty acids (FFA, the last one is an independent risk factor for IR. It has been clear that FFA may induce IR by endoplasmic reticulum (ER stress, oxidative stress, apoptosis and inflammation, although the specific mechanisms remained unknown. The present paper summarizes the related molecules involved in the pathogenic process of IR and its mechanism, might provide a theoretical basis for the molecular mechanism of IR caused by FFA, and therapeutic reference for clinical treatment of IR and prevention of T2DM. DOI: 10.11855/j.issn.0577-7402.2017.01.16

  17. Two-Component Systems Involved in Susceptibility to Nisin A in Streptococcus pyogenes.

    Science.gov (United States)

    Kawada-Matsuo, Miki; Tatsuno, Ichiro; Arii, Kaoru; Zendo, Takeshi; Oogai, Yuichi; Noguchi, Kazuyuki; Hasegawa, Tadao; Sonomoto, Kenji; Komatsuzawa, Hitoshi

    2016-10-01

    Two-component systems (TCSs) are regulatory systems in bacteria that play important roles in sensing and adapting to the environment. In this study, we systematically evaluated the roles of TCSs in the susceptibility of the group A Streptococcus (GAS; Streptococcus pyogenes) SF370 strain to several types of lantibiotics. Using individual TCS deletion mutants, we found that the deletion of srtRK (spy_1081-spy_1082) in SF370 increased the susceptibility to nisin A, which is produced by Lactococcus lactis ATCC 11454, but susceptibility to other types of lantibiotics (nukacin ISK-1, produced by Staphylococcus warneri, and staphylococcin C55, produced by Staphylococcus aureus) was not altered in the TCS mutants tested. The expression of srtFEG (spy_1085 to spy_1087), which is located downstream of srtRK and is homologous to ABC transporters, was increased in response to nisin A. However, srtEFG expression was not induced by nisin A in the srtRK mutant. The inactivation of srtFEG increased the susceptibility to nisin A. These results suggest that SrtRK controls SrtFEG expression to alter the susceptibility to nisin A. Further experiments showed that SrtRK is required for coexistence with L. lactis ATCC 11454, which produces nisin A. Our results elucidate the important roles of S. pyogenes TCSs in the interactions between different bacterial species, including bacteriocin-producing bacteria. In this study, we focused on the association of TCSs with susceptibility to bacteriocins in S. pyogenes SF370, which has no ability to produce bacteriocins, and reported two major new findings. We demonstrated that the SrtRK TCS is related to susceptibility to nisin A by controlling the ABC transporter SrtFEG. We also showed that S. pyogenes SrtRK is important for survival when the bacteria are cocultured with nisin A-producing Lactococcus lactis This report highlights the roles of TCSs in the colocalization of bacteriocin-producing bacteria and non-bacteriocin-producing bacteria. Our

  18. Mechanisms of resistance in nontyphoidal Salmonella enterica strains exhibiting a nonclassical quinolone resistance phenotype.

    Science.gov (United States)

    Gunell, Marianne; Webber, Mark A; Kotilainen, Pirkko; Lilly, Andrew J; Caddick, Jonathan M; Jalava, Jari; Huovinen, Pentti; Siitonen, Anja; Hakanen, Antti J; Piddock, Laura J V

    2009-09-01

    Nontyphoidal Salmonella enterica strains with a nonclassical quinolone resistance phenotype were isolated from patients returning from Thailand or Malaysia to Finland. A total of 10 isolates of seven serovars were studied in detail, all of which had reduced susceptibility (MIC > or = 0.125 microg/ml) to ciprofloxacin but were either susceptible or showed only low-level resistance (MIC resistance-determining regions (QRDR) of gyrA, gyrB, parC, and parE by PCR and denaturing high-pressure liquid chromatography and the amplification of plasmid-mediated quinolone resistance (PMQR) genes qnrA, qnrB, qnrS, qnrD, aac(6')-Ib-cr, and qepA by PCR. PMQR was confirmed by plasmid analysis, Southern hybridization, and plasmid transfer. No mutations in the QRDRs of gyrA, gyrB, parC, or parE were detected with the exception of a Thr57-Ser substitution within ParC seen in all but the S. enterica serovar Typhimurium strains. The qnrA and qnrS genes were the only PMQR determinants detected. Plasmids carrying qnr alleles were transferable in vitro, and the resistance phenotype was reproducible in Escherichia coli DH5alpha transformants. These data demonstrate the emergence of a highly mobile qnr genotype that, in the absence of mutation within topoisomerase genes, confers the nontypical quinolone resistance phenotype in S. enterica isolates. The qnr resistance mechanism enables bacteria to survive elevated quinolone concentrations, and therefore, strains carrying qnr alleles may be able to expand during fluoroquinolone treatment. This is of concern since nonclassical quinolone resistance is plasmid mediated and therefore mobilizable.

  19. Mycoplasma bovis: mechanisms of resistance and trends in antimicrobial susceptibility

    Directory of Open Access Journals (Sweden)

    Inna eLysnyansky

    2016-04-01

    Full Text Available Mycoplasma bovis is a cell-wall-less bacterium and belongs to the class Mollicutes. It is the most important etiological agent of bovine mycoplasmoses in North America and Europe, causing respiratory disease, mastitis, otitis media, arthritis, and reproductive disease. Clinical disease associated with M. bovis is often chronic, debilitating, and poorly responsive to antimicrobial therapy, resulting in significant economic loss, the full extent of which is difficult to estimate. Until M. bovis vaccines are universally available, sanitary control measures and antimicrobial treatment are the only approaches that can be used in attempts to control M. bovis infections. However, in vitro studies show that many of the current M. bovis isolates circulating in Europe have high minimum inhibitory concentrations (MIC for many of the commercially available antimicrobials. In this review we summarize the current MIC trends indicating the development of antimicrobial resistance in M. bovis as well as the known molecular mechanisms by which resistance is acquired.

  20. Approved Glycopeptide Antibacterial Drugs: Mechanism of Action and Resistance.

    Science.gov (United States)

    Zeng, Daina; Debabov, Dmitri; Hartsell, Theresa L; Cano, Raul J; Adams, Stacy; Schuyler, Jessica A; McMillan, Ronald; Pace, John L

    2016-12-01

    The glycopeptide antimicrobials are a group of natural product and semisynthetic glycosylated peptides that show antibacterial activity against Gram-positive organisms through inhibition of cell-wall synthesis. This is achieved primarily through binding to the d-alanyl-d-alanine terminus of the lipid II bacterial cell-wall precursor, preventing cross-linking of the peptidoglycan layer. Vancomycin is the foundational member of the class, showing both clinical longevity and a still preferential role in the therapy of methicillin-resistant Staphylococcus aureus and of susceptible Enterococcus spp. Newer lipoglycopeptide derivatives (telavancin, dalbavancin, and oritavancin) were designed in a targeted fashion to increase antibacterial activity, in some cases through secondary mechanisms of action. Resistance to the glycopeptides emerged in delayed fashion and occurs via a spectrum of chromosome- and plasmid-associated elements that lead to structural alteration of the bacterial cell-wall precursor substrates. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  1. Mechanisms of reef coral resistance to future climate change.

    Science.gov (United States)

    Palumbi, Stephen R; Barshis, Daniel J; Traylor-Knowles, Nikki; Bay, Rachael A

    2014-05-23

    Reef corals are highly sensitive to heat, yet populations resistant to climate change have recently been identified. To determine the mechanisms of temperature tolerance, we reciprocally transplanted corals between reef sites experiencing distinct temperature regimes and tested subsequent physiological and gene expression profiles. Local acclimatization and fixed effects, such as adaptation, contributed about equally to heat tolerance and are reflected in patterns of gene expression. In less than 2 years, acclimatization achieves the same heat tolerance that we would expect from strong natural selection over many generations for these long-lived organisms. Our results show both short-term acclimatory and longer-term adaptive acquisition of climate resistance. Adding these adaptive abilities to ecosystem models is likely to slow predictions of demise for coral reef ecosystems. Copyright © 2014, American Association for the Advancement of Science.

  2. Mycoplasma bovis: Mechanisms of Resistance and Trends in Antimicrobial Susceptibility.

    Science.gov (United States)

    Lysnyansky, Inna; Ayling, Roger D

    2016-01-01

    Mycoplasma bovis is a cell-wall-less bacterium and belongs to the class Mollicutes. It is the most important etiological agent of bovine mycoplasmoses in North America and Europe, causing respiratory disease, mastitis, otitis media, arthritis, and reproductive disease. Clinical disease associated with M. bovis is often chronic, debilitating, and poorly responsive to antimicrobial therapy, resulting in significant economic loss, the full extent of which is difficult to estimate. Until M. bovis vaccines are universally available, sanitary control measures and antimicrobial treatment are the only approaches that can be used in attempts to control M. bovis infections. However, in vitro studies show that many of the current M. bovis isolates circulating in Europe have high minimum inhibitory concentrations (MIC) for many of the commercially available antimicrobials. In this review we summarize the current MIC trends indicating the development of antimicrobial resistance in M. bovis as well as the known molecular mechanisms by which resistance is acquired.

  3. Rapid diagnosis of tuberculosis. Detection of drug resistance mechanisms.

    Science.gov (United States)

    Viñuelas-Bayón, Jesús; Vitoria, María Asunción; Samper, Sofía

    2017-10-01

    Tuberculosis is still a serious public health problem, with 10.8 million new cases and 1.8 million deaths worldwide in 2015. The diversity among members of the Mycobacterium tuberculosis complex, the causal agent of tuberculosis, is conducive to the design of different methods for rapid diagnosis. Mutations in the genes involved in resistance mechanisms enable the bacteria to elude the treatment. We have reviewed the methods for the rapid diagnosis of M. tuberculosis complex and the detection of susceptibility to drugs, both of which are necessary to prevent the onset of new resistance and to establish early, appropriate treatment. Copyright © 2017 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  4. In Vitro Characterization and Evaluation of the Cytotoxicity Effects of Nisin and Nisin-Loaded PLA-PEG-PLA Nanoparticles on Gastrointestinal (AGS and KYSE-30), Hepatic (HepG2) and Blood (K562) Cancer Cell Lines.

    Science.gov (United States)

    Goudarzi, Fariba; Asadi, Asadollah; Afsharpour, Maryam; Jamadi, Robab Hassanvand

    2018-02-22

    The aim of this study was an in vitro evaluation and comparison of the cytotoxic effects of free nisin and nisin-loaded PLA-PEG-PLA nanoparticles on gastrointestinal (AGS and KYSE-30), hepatic (HepG2), and blood (K562) cancer cell lines. To create this novel anti-cancer drug delivery system, the nanoparticles were synthesized and then loaded with nisin. Subsequently, their biocompatibility, ability to enter cells, and physicochemical properties, including formation, size, and shape, were studied using hemolysis, fluorescein isothiocyanate (FITC), Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), and scanning electron microscopy (SEM), respectively. Then, its loading efficiency and release kinetics were examined to assess the potential impact of this formulation for the nanoparticle carrier candidacy. The cytotoxicities of nisin and nisin-loaded nanoparticles were evaluated by using the MTT and Neutral Red (NR) uptake assays. Detections of the apoptotic cells were done via Ethidium Bromide (EB)/Acridine Orange (AO) staining. The FTIR spectra, SEM images, and DLS graph confirmed the formations of the nanoparticles and nisin-loaded nanoparticles with spherical, distinct, and smooth surfaces and average sizes of 100 and 200 nm, respectively. The loading efficiency of the latter nanoparticles was about 85-90%. The hemolysis test represented their non-cytotoxicities and the FITC images indicated their entrance inside the cells. An increase in the percentage of apoptotic cells was observed through EB/AO staining. These results demonstrated that nisin had a cytotoxic effect on AGS, KYSE-30, HepG2, and K562 cancer cell lines, while the cytotoxicity of nisin-loaded nanoparticles was more than that of the free nisin.

  5. Infection control implications of heterogeneous resistance mechanisms in carbapenem-resistant Enterobacteriaceae (CRE).

    Science.gov (United States)

    Goodman, K E; Simner, P J; Tamma, P D; Milstone, A M

    2016-01-01

    The Centers for Disease Control and Prevention (CDC) defines carbapenem-resistant Enterobacteriaceae (CRE) based upon a phenotypic demonstration of carbapenem resistance. However, considerable heterogeneity exists within this definitional umbrella. CRE may mechanistically differ by whether they do or do not produce carbapenemases. Moreover, patients can acquire CRE through multiple pathways: endogenously through antibiotic selective pressure on intestinal microbiota, exogenously through horizontal transmission or through a combination of these factors. Some evidence suggests that non-carbapenemase-producing CRE may be more frequently acquired by antibiotic exposure and carbapenemase-producing CRE via horizontal transmission, but definitive data are lacking. This review examines types of CRE resistance mechanisms, antibiotic exposure and horizontal transmission pathways of CRE acquisition, and the implications of these heterogeneities to the development of evidence-based CRE healthcare epidemiology policies. In our Expert Commentary & Five-Year View, we outline specific nosocomial CRE knowledge gaps and potential methodological approaches for their resolution.

  6. Mechanisms accounting for fluoroquinolone resistance in Escherichia coli clinical isolates.

    Science.gov (United States)

    Morgan-Linnell, Sonia K; Becnel Boyd, Lauren; Steffen, David; Zechiedrich, Lynn

    2009-01-01

    Fluoroquinolone MICs are increased through the acquisition of chromosomal mutations in the genes encoding gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE), increased levels of the multidrug efflux pump AcrAB, and the plasmid-borne genes aac(6')-Ib-cr and the qnr variants in Escherichia coli. In the accompanying report, we found that ciprofloxacin, gatifloxacin, levofloxacin, and norfloxacin MICs for fluoroquinolone-resistant E. coli clinical isolates were very high and widely varied (L. Becnel Boyd, M. J. Maynard, S. K. Morgan-Linnell, L. B. Horton, R. Sucgang, R. J. Hamill, J. Rojo Jimenez, J. Versalovic, D. Steffen, and L. Zechiedrich, Antimicrob. Agents Chemother. 53:229-234, 2009). Here, we sequenced gyrA, gyrB, parC, and parE; screened for aac(6')-Ib-cr and qnrA; and quantified AcrA levels in E. coli isolates for which patient sex, age, location, and site of infection were known. We found that (i) all fluoroquinolone-resistant isolates had gyrA mutations; (ii) approximately 85% of gyrA mutants also had parC mutations; (iii) the ciprofloxacin and norfloxacin MICs for isolates harboring aac(6')-Ib-cr ( approximately 23%) were significantly higher, but the gatifloxacin and levofloxacin MICs were not; (iv) no isolate had qnrA; and (v) approximately 33% of the fluoroquinolone-resistant isolates had increased AcrA levels. Increased AcrA correlated with nonsusceptibility to the fluoroquinolones but did not correlate with nonsusceptibility to any other antimicrobial agents reported from hospital antibiograms. Known mechanisms accounted for the fluoroquinolone MICs of 50 to 70% of the isolates; the remaining included isolates for which the MICs were up to 1,500-fold higher than expected. Thus, additional, unknown fluoroquinolone resistance mechanisms must be present in some clinical isolates.

  7. Mechanisms Accounting for Fluoroquinolone Resistance in Escherichia coli Clinical Isolates▿

    Science.gov (United States)

    Morgan-Linnell, Sonia K.; Becnel Boyd, Lauren; Steffen, David; Zechiedrich, Lynn

    2009-01-01

    Fluoroquinolone MICs are increased through the acquisition of chromosomal mutations in the genes encoding gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE), increased levels of the multidrug efflux pump AcrAB, and the plasmid-borne genes aac(6′)-Ib-cr and the qnr variants in Escherichia coli. In the accompanying report, we found that ciprofloxacin, gatifloxacin, levofloxacin, and norfloxacin MICs for fluoroquinolone-resistant E. coli clinical isolates were very high and widely varied (L. Becnel Boyd, M. J. Maynard, S. K. Morgan-Linnell, L. B. Horton, R. Sucgang, R. J. Hamill, J. Rojo Jimenez, J. Versalovic, D. Steffen, and L. Zechiedrich, Antimicrob. Agents Chemother. 53:229-234, 2009). Here, we sequenced gyrA, gyrB, parC, and parE; screened for aac(6′)-Ib-cr and qnrA; and quantified AcrA levels in E. coli isolates for which patient sex, age, location, and site of infection were known. We found that (i) all fluoroquinolone-resistant isolates had gyrA mutations; (ii) ∼85% of gyrA mutants also had parC mutations; (iii) the ciprofloxacin and norfloxacin MICs for isolates harboring aac(6′)-Ib-cr (∼23%) were significantly higher, but the gatifloxacin and levofloxacin MICs were not; (iv) no isolate had qnrA; and (v) ∼33% of the fluoroquinolone-resistant isolates had increased AcrA levels. Increased AcrA correlated with nonsusceptibility to the fluoroquinolones but did not correlate with nonsusceptibility to any other antimicrobial agents reported from hospital antibiograms. Known mechanisms accounted for the fluoroquinolone MICs of 50 to 70% of the isolates; the remaining included isolates for which the MICs were up to 1,500-fold higher than expected. Thus, additional, unknown fluoroquinolone resistance mechanisms must be present in some clinical isolates. PMID:18838592

  8. Resistant mechanism study of benzalkonium chloride selected Salmonella Typhimurium mutants.

    Science.gov (United States)

    Guo, Wei; Cui, Shenghui; Xu, Xiao; Wang, Haoyan

    2014-02-01

    Benzalkonium chloride is one of the invaluable biocides that is extensively used in healthcare settings as well as in the food processing industry. After exposing wild-type Salmonella Typhimurium 14028s or its AcrAB inactivation mutant to gradually increasing levels of benzalkonium chloride, resistance mutants S-41, S-150, S-AB-23, S-AB-38, and S-AB-73 were selected and these mutants also showed a 2-64-fold stable minimum inhibitory concentration (MIC) increase to chloramphenicol, ciprofloxacin, nalidixic acid, and tetracycline. In S-41 and S-150, the expression of acrB was increased 2.7- and 7.6-fold, and ΔtolC or ΔacrAB mutants of S-41 and S-150 showed the same MICs to all tested antimicrobials as the equivalent Salmonella Typhimurium 14028s mutants. However, in S-AB-23, S-AB-38, and S-AB-73, the expression of acrF was increased 96-, 230-, and 267-fold, respectively, and ΔtolC or ΔacrEF mutants of S-AB-23, S-AB-38, and S-AB-73 showed the similar MICs to all tested antimicrobials as the ΔtolC mutant of Salmonella Typhimurium 14028s. Our data showed that constitutively over-expressed AcrAB working through TolC was the main resistance mechanism in ST14028s benzalkonium chloride resistance mutants. However, after AcrAB had been inactivated, benzalkonium chloride-resistant mutants could still be selected and constitutively over-expressed, AcrEF became the dominant efflux pump working through TolC and being responsible for the increasing antimicrobial resistance. These data indicated that different mechanisms existed for acrB and acrF constitutive over-expression. Since exposure to benzalkonium chloride may lead to Salmonella mutants with a decreased susceptibility to quinolones, which is currently one of the drugs of choice for the treatment of life-threatening salmonelosis, research into the pathogenesis and epidemiology of the benzalkonium chloride resistance mutants will be of increasing importance.

  9. Nanoparticle mechanics: deformation detection via nanopore resistive pulse sensing

    Science.gov (United States)

    Darvish, Armin; Goyal, Gaurav; Aneja, Rachna; Sundaram, Ramalingam V. K.; Lee, Kidan; Ahn, Chi Won; Kim, Ki-Bum; Vlahovska, Petia M.; Kim, Min Jun

    2016-07-01

    Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various liposomes inside nanopores. We observed a significant difference in resistive pulse characteristics between soft liposomes and rigid polystyrene nanoparticles especially at higher applied voltages. We used theoretical simulations to demonstrate that the difference can be explained by shape deformation of liposomes as they translocate through the nanopores. Comparing our results with the findings from electrodeformation experiments, we demonstrated that the rigidity of liposomes can be qualitatively compared using resistive pulse characteristics. This application of nanopores can provide new opportunities to study the mechanics at the nanoscale, to investigate properties of great value in fundamental biophysics and cellular mechanobiology, such as virus deformability and fusogenicity, and in applied sciences for designing novel drug/gene delivery systems.Solid-state nanopores have been widely used in the past for single-particle analysis of nanoparticles, liposomes, exosomes and viruses. The shape of soft particles, particularly liposomes with a bilayer membrane, can greatly differ inside the nanopore compared to bulk solution as the electric field inside the nanopores can cause liposome electrodeformation. Such deformations can compromise size measurement and characterization of particles, but are often neglected in nanopore resistive pulse sensing. In this paper, we investigated the deformation of various

  10. Antimicrobial Combinations against Pan-Resistant Acinetobacter baumannii Isolates with Different Resistance Mechanisms.

    Directory of Open Access Journals (Sweden)

    Gleice Cristina Leite

    Full Text Available The study investigated the effect of antibiotic combinations against 20 clinical isolates of A. baumannii (seven colistin-resistant and 13 colistin-susceptible with different resistance mechanisms. Clinical data, treatment, and patient mortality were evaluated. The following methods were used: MIC, PCRs, and outer membrane protein (OMP analysis. Synergy was investigated using the checkerboard and time-kill methods. Clonality was evaluated by PFGE. Based on clonality, the whole genome sequence of six A. baumannii isolates was analyzed. All isolates were resistant to meropenem, rifampicin, and fosfomycin. OXA-23 and OXA-143 were the most frequent carbapenemases found. Four isolates showed loss of a 43kDa OMP. The colistin-susceptible isolates belonged to different clones and showed the highest synergistic effect with fosfomycin-amikacin. Among colistin-resistant isolates, the highest synergistic effect was observed with the combinations of colistin-rifampicin followed by colistin-vancomycin. All colistin-resistant isolates harbored blaOXA-23-like and belonged to CC113. Clinical and demographic data were available for 18 of 20 patients. Fourteen received treatment and eight patients died during treatment. The most frequent site of infection was the blood in 13 of 14 patients. Seven patients received vancomycin plus an active drug against A. baumannii; however, mortality did not differ in this group. The synergistic effect was similar for colistin-susceptible isolates of distinct clonal origin presenting with the same resistance mechanism. Overall mortality and death during treatment was high, and despite the high synergism in vitro with vancomycin, death did not differ comparing the use or not of vancomycin plus an active drug against A. baumannii.

  11. Preparation and optimization of self-assembled chondroitin sulfate-nisin nanogel based on quality by design concept.

    Science.gov (United States)

    Mohtashamian, Shahab; Boddohi, Soheil; Hosseinkhani, Saman

    2018-02-01

    Self-assembled nanogel was prepared by electrostatic complexation of two oppositely charged biological macromolecules, which were cationic nisin and anionic chondroitin sulfate (ChS). The critical factors affected the physical properties of ChS-nisin nanogel was screened and optimized by Plackett-Burman design (PB) and central composite design (CCD). The independent factors selected were: concentration ratio of nisin to ChS, injection rate of nisin solution, buffer solvent type, magnetic stirring rate, pH of initial buffer solution, centrifuge-cooling temperature, and centrifuge rotation speed. Among these factors, concentration ratio changed the entrapment efficiency and loading capacity significantly. In addition, the hydrodynamic diameter and loading capacity were significantly influenced by injection rate and pH of initial buffer solution. The optimized nanogel structure was obtained by concentration ratio of 6.4mg/mL nisin to 1mg/mL ChS, pH of buffer solution at 4.6, and nisin solution injection rate of 0.2mL/min. The observed values of dependent responses were close to predicted values confirmed by model from response surface methodology. The results obviously showed that quality by design concept (QbD) could be effectively applied to optimize the developed ChS-nisin nanogel. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Synthesis of antimicrobial Nisin-phosphorylated soybean protein isolate/poly(L-lactic acid)/ZrO2 membranes.

    Science.gov (United States)

    Jiang, Suwei; Wang, Hualin; Chu, Chenjiang; Ma, Xingkong; Sun, Min; Jiang, Shaotong

    2015-01-01

    Electrospinning technique was used to fabricate the model drug Nisin loaded phosphorylated soybean protein isolate/poly(l-lactic acid)/zirconium dioxide (Nisin-PSPI/PLLA/ZrO2) nanofibrous membranes. The average diameter of drug carrier PSPI/PLLA/ZrO2 nanofibers increased with the increase of content PSPI and some spindle-shape beads appeared when PSPI content reached 25 wt%. The loading dosage of Nisin caused no significant changes in the size and morphology of nanofibers when Nisin content was below 9 wt%. There existed hydrogen and Zr-O-C bonds among PSPI, PLLA and ZrO2 units, and the crystalline of PLLA matrix decreased owning to the introducing of PSPI and ZrO2 units. Moreover, the water absorption capability and degradation rate of PSPI/PLLA/ZrO2 nanofibrous membranes increased with increasing PSPI content. The antimicrobial activity and release experimental results showed that Nisin-PSPI/PLLA/ZrO2 nanofibrous membranes displayed well controlled release and better antimicrobial activity against Staphylococcus aureus (S. aureus), and the Nisin release from the medicated nanofibers could be described by Fickian diffusion model. The Nisin-PSPI/PLLA/ZrO2 nanofibrous membranes may have potential as a new nanofibrous membrane in drug delivery, food active packaging and wound dressing. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. Corrosion resistance of zirconium: general mechanisms, behaviour in nitric acid

    International Nuclear Information System (INIS)

    Pinard Legry, G.

    1990-01-01

    Corrosion resistance of zirconium results from the strong affinity of this metal for oxygen; as a result a thin protective oxide film is spontaneously formed in air or aqueous media, its thickness and properties depending on the physicochemical conditions at the interface. This film passivates the underlying metal but obviously if the passive film is partially or completely removed, localised or generalised corrosion phenomena will occur. In nitric acid, this depassivation may be chemical (fluorides) or mechanical (straining, creep, fretting). In these cases it is useful to determine the physicochemical conditions (concentration, temperature, potential, stress) which will have to be observed to use safely zirconium and its alloys in nitric acid solutions [fr

  14. Mechanism of corrosion resistance for C + W dual implanted steel

    International Nuclear Information System (INIS)

    Zhang Tonghe; Wu Yuguang; Liu Andong; Zhang Xu; Wang Xiaoyan

    2003-01-01

    The properties of corrosion resistance for C and W dual-implanted H13 steel were studied using multi-sweep cyclic voltammetry. The corrosion morphologies were investigated by scanning electron microscopy (SEM). The results show that after corrosion for 30 voltage scanning-loops, serious corrosion morphology appears on the surface of H13 steel: dense corrosion pits are distributed on the surface. Both shape and distribution morphology of these pits indicate the crystal properties: some pits are triangle or rectangle, and the pits are located along grain boundaries. But after corrosion of the W and C dual implanted steel samples, surface corrosion pits are shallow and small. Shallow corrosion pits are dislocated random, their shape and distribution are not provided with crystal properties. When the fluence is increased and after corrosion for 88 voltage scanning-loops, the surface corrosion pits are still shallow and small, showing the corrosion resistance to be enhanced further. Finally the mechanism of corrosion resistance was discussed

  15. Mechanisms of Brain Glucocorticoid Resistance in Stress-Induced Psychopathologies.

    Science.gov (United States)

    Merkulov, V M; Merkulova, T I; Bondar, N P

    2017-03-01

    Exposure to stress activates the hypothalamic-pituitary-adrenal axis and leads to increased levels of glucocorticoid (GC) hormones. Prolonged elevation of GC levels causes neuronal dysfunction, decreases the density of synapses, and impairs neuronal plasticity. Decreased sensitivity to glucocorticoids (glucocorticoid resistance) that develops as a result of chronic stress is one of the characteristic features of stress-induced psychopathologies. In this article, we reviewed the published data on proposed molecular mechanisms that contribute to the development of glucocorticoid resistance in brain, including changes in the expression of the glucocorticoid receptor (GR) gene, biosynthesis of GR isoforms, and GR posttranslational modifications. We also present data on alterations in the expression of the FKBP5 gene encoding the main component of cell ultra-short negative feedback loop of GC signaling regulation. Recent discoveries on stress- and GR-induced changes in epigenetic modification patterns as well as normalizing action of antidepressants are discussed. GR and FKBP5 gene polymorphisms associated with stress-induced psychopathologies are described, and their role in glucocorticoid resistance is discussed.

  16. The molecular mechanism linking muscle fat accumulation to insulin resistance.

    Science.gov (United States)

    Hulver, Matthew W; Dohm, G Lynis

    2004-05-01

    Skeletal muscle insulin resistance is a co-morbidity of obesity and a risk factor for the development of type 2 diabetes mellitus. Insulin resistance is associated with the accumulation of intramyocellular lipids. Intramyocellular triacylglycerols do not appear to be the cause of insulin resistance but are more likely to be a marker of other lipid intermediates such as fatty acyl-CoA, ceramides or diacylglycerols. Fatty acyl-CoA, ceramides and diacylglycerols are known to directly alter various aspects of the insulin signalling cascade. Insulin signalling is inhibited by the phosphorylation of serine and threonine residues at the levels of the insulin receptor and insulin receptor substrate 1. Protein kinase C is responsible for the phosphorylation of the serine and threonine residues. Fatty acyl-CoA and diacylglycerols are known to activate protein kinase C. The cause of the intramyocellular accumulation of fatty acyl-CoA and diacylglycerols is unclear at this time. Reduced fatty acid oxidation does not appear to be responsible, as fatty acyl-CoA accumulates in skeletal muscle with a normal fatty acid oxidative capacity. Other potential mechanisms include oversupply of lipids to muscle and/or up regulated fatty acid transport.

  17. The nisin improves broiler chicken growth performance and interacts with salinomycin in terms of gastrointestinal tract microbiota composition

    DEFF Research Database (Denmark)

    Kieronczyk, B; Pruszyńska-Oszmałek, E; Swiatkiewicz, S

    2016-01-01

    as: NA – no additives, SAL – salinomycin (60 mg · kg−1 diet), NIS – nisin (2700 IU · kg−1 diet) were used. Nisin addition in comparison to salinomycin and control treatments, improved body weight gain in the entire experiment (days 1–35) as well as increased feed intake and decreased feed conversion......, Lactobacillus spp. Enterococcus spp., Clostridium coccoides–Eubacterium rectale cluster and increasing signals from Bifidobacterium spp. as well as Streptococcus sp. Lactococcus. There were no interactions between nisin and salinomycin in terms of organic acids concentration in the crop, gizzard, ileum...

  18. Effects of Lactococcus lactis on composition of intestinal microbiota: Role of nisin

    DEFF Research Database (Denmark)

    Bernbom, Nete; Licht, Tine Rask; Brogren, Carl-Henrik

    2006-01-01

    in the rat fecal microbiota were observed after dosage with nisin. Pearson cluster analysis of denaturing gradient gel electrophoresis profiles of the 16S rRNA genes present in the fecal microbial population revealed that the microbiota of animals dosed with either of the two L. lactis strains were different...

  19. Effects of nisin on the antimicrobial activity of d-limonene and its nanoemulsion.

    Science.gov (United States)

    Zhang, Zijie; Vriesekoop, Frank; Yuan, Qipeng; Liang, Hao

    2014-05-01

    d-Limonene has been considered to be a safer alternative compared to synthetic antimicrobial food additives. However, its hydrophobic and oxidative nature has limited its application in foods. The purpose of this research was to study effects of nisin on the antimicrobial activity of d-limonene and its nanoemulsion and develop a novel antimicrobial delivery system by combining the positive effect of these two antibacterial agents at the same time. By the checkerboard method, both the synergistic and additive effects of d-limonene and nisin were found against four selected food-related microorganisms. Then, d-limonene nanoemulsion with or without nisin was prepared by catastrophic phase inversion method, which has shown good droplet size and stability. The positive effects and outstanding antimicrobial activity of d-limonene nanoemulsion with nisin were confirmed by MICs comparison, scanning electron microscopy and determination of cell constituents released. Overall, the research described in the current article would be helpful in developing a more effective antimicrobial system for the production and preservation of foods. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  20. The effect of nisin from Lactococcus lactis subsp. lactis on refrigerated patin fillet quality

    Science.gov (United States)

    Adilla, S. N.; Utami, R.; Nursiwi, A.; Nurhartadi, E.

    2017-04-01

    The effect of nisin from Lactococcus lactis subsp. lactis with spraying method application on quality of patin fillet during refrigerated storage (4±1°C) was investigated. The quality of patin fillet based on total plate count (TPC), pH, TVB-N, and TBA values during 16 days at 4±1°C. Completely Randomized Design (CDR) was used in one factor (nisin activity) at 0 IU/ml, 500 IU/ml, 1000 IU/ml, and 2000 IU/ml. The observation was done at 0, 4th, 8th, 12th, and 16th days of storage. The result showed that variation of nisin activity significantly affected the quality of fillet according to TPC, pH, and TVB-N values, however no significant difference on the obtained of TBA value. Nisin in 500 IU/ml, 1000 IU/ml, and 2000 IU/ml could extend the shelf-life of fillet until 4th, 8th, and 12th days respectively based on standard in all parameters.

  1. Nisin-induced Expression of Pediocin in Dairy Lactic Acid Bacteria

    Science.gov (United States)

    To test if a single vector, nisin-controlled expression (NICE) system could be used to regulate expression of the pediocin operon in Streptococcus thermophilus, Lactococcus lactis subsp. lactis and Lactobacillus casei, the intact pediocin operon was cloned into pMSP3535 immediately down stream of th...

  2. Combinations of nisin with salt (NaCl) to control Listeria ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-02-22

    Feb 22, 2010 ... 59: 223–228. Coma V, Sebti I, Pardon P, Deschamps A, Pichavant FH (2001). Antimicrobial 357 edible packaging based on cellulosic ethers, fatty acids and nisin incorporation to inhibit Listeria innocua and. Staphylococcus aureus. J. Food Prot. 64: 470–475. Conner DE, Brackett RE, Beuchat LR (1986).

  3. Transmission electron microscopy of Listeria innocua treated by pulsed electric fields and nisin in skimmed milk.

    Science.gov (United States)

    Calderón-Miranda, M L; Barbosa-Cánovas, G V; Swanson, B G

    1999-10-01

    Pulsed electric fields (PEF) is a nonthermal food preservation process where organoleptic and nutritional properties of the food are maintained. PEF is known to inactivate microorganisms by causing dielectric breakdown of the cell membrane, thus altering the functionality of the membrane as a semipermeable barrier. The extent of damage of the cell membrane, whether visible in the form of a pore or as loss of membrane functionality leads to the inactivation of the microorganism. The objective of this study was to investigate under transmission electron microscopy (TEM) the morphological changes on Listerit innocua as a result of PEF treatment in skimmed milk containing nisin. L. innocua was subjected to PEF at selected electric field intensities of 30, 40, and 50 kV/cm. L. innocua was treated by PEF in both skimmed milk with and without 37 IU nisin/ml. L. innocua treated by PEF in skimmed milk exhibited an increase in the cell wall roughness. cytoplasmic clumping, leakage of cellular material, and rupture of the cell walls and cell membranes. L. innocua subjected to PEF in skimmed milk containing 37 IU nisin/ml exhibited an increased cell wall width. At the highest electric field intensity, 50 kV/cm, elongation of the cell length was observed. There were no morphological differences between cells treated by PEF in skimmed milk with or without nisin. The combination of PEF and nisin exhibit an additive effect in the morphological damage observed on L. innocua. Pore formation was observed on L. innocua for an electric field intensity of 40 kV/cm. The inactivation of L. innocua was a consequence of rupture of the cell membrane and loss of cell membrane functionality.

  4. Inhibition of Bacillus licheniformis spore growth in milk by nisin, monolaurin, and pH combinations.

    Science.gov (United States)

    Mansour, M; Amri, D; Bouttefroy, A; Linder, M; Milliere, J B

    1999-02-01

    The effects of nisin and monolaurin, alone and in combination, were investigated on Bacillus licheniformis spores in milk at 37 degrees C. In the absence of inhibitors, germinated spores developed into growing vegetative cells and started sporulation at the end of the exponential phase. In the presence of nisin (25 IU ml-1), spore outgrowth was inhibited (4 log10 reduction at 10 h). Regrowth appeared between 10 and 24 h and reached a high population level (1.25 x 10(8) cfu ml-1) after 7 d. Monolaurin (250 micrograms ml-1) had a bacteriostatic effect during the first 10 h but thereafter, regrowth occurred slowly with a population level after 7 d (4 x 10(5) cfu ml-1) lower than that of nisin. Different combined effects of nisin (between 0 and 42 IU ml-1), monolaurin (ranging from 0 to 300 micrograms ml-1), pH values (between 5.0 and 7.0) and spore loads (10(3), 10(4), 10(5) spores ml-1) were investigated using a Doehlert matrix in order to study the main effects of these factors and the different interactions. Results were analysed using the Response Surface Methodology (RSM) and indicated that nisin and monolaurin had no action on spores before germination; only pH values had a significant effect (P monolaurin (100 micrograms ml-1) in combination acted synergistically on outgrown spores and vegetative cells, showing total inhibition at pH 6.0, without regrowth, within 7 d at 37 degrees C.

  5. Optimization of the Lactococcus lactis nisin-controlled gene expression system NICE for industrial applications

    Directory of Open Access Journals (Sweden)

    Mond James

    2005-05-01

    Full Text Available Abstract Background The nisin-controlled gene expression system NICE of Lactococcus lactis is one of the most widely used expression systems in Gram-positive bacteria. Despite its widespread use, no optimization of the culture conditions and nisin induction has been carried out to obtain maximum yields. As a model system induced production of lysostaphin, an antibacterial protein (mainly against Staphylococcus aureus produced by S. simulans biovar. Staphylolyticus, was used. Three main areas need optimization for maximum yields: cell density, nisin-controlled induction and protein production, and parameters specific for the target-protein. Results In a series of pH-controlled fermentations the following parameters were optimized: pH of the culture, use of NaOH or NH4OH as neutralizing agent, the addition of zinc and phosphate, the fermentation temperature, the time point of induction (cell density of the culture, the amount of nisin added for induction and the amount of three basic medium components, i.e. yeast extract, peptone and lactose. For each culture growth and lysostaphin production was followed. Lysostaphin production yields depended on all parameters that were varied. In the course of the optimization a three-fold increase in lysostaphin yield was achieved from 100 mg/l to 300 mg/l. Conclusion Protein production with the NICE gene expression system in L. lactis strongly depends on the medium composition, the fermentation parameters and the amount of nisin added for induction. Careful optimization of key parameters lead to a significant increase in the yield of the target protein.

  6. Mechanisms of virus resistance and antiviral activity of snake venoms

    Directory of Open Access Journals (Sweden)

    JVR Rivero

    2011-01-01

    Full Text Available Viruses depend on cell metabolism for their own propagation. The need to foster an intimate relationship with the host has resulted in the development of various strategies designed to help virus escape from the defense mechanisms present in the host. Over millions of years, the unremitting battle between pathogens and their hosts has led to changes in evolution of the immune system. Snake venoms are biological resources that have antiviral activity, hence substances of significant pharmacological value. The biodiversity in Brazil with respect to snakes is one of the richest on the planet; nevertheless, studies on the antiviral activity of venom from Brazilian snakes are scarce. The antiviral properties of snake venom appear as new promising therapeutic alternative against the defense mechanisms developed by viruses. In the current study, scientific papers published in recent years on the antiviral activity of venom from various species of snakes were reviewed. The objective of this review is to discuss the mechanisms of resistance developed by viruses and the components of snake venoms that present antiviral activity, particularly, enzymes, amino acids, peptides and proteins.

  7. Mechanisms of Metal Resistance and Homeostasis in Haloarchaea

    Science.gov (United States)

    Srivastava, Pallavee; Kowshik, Meenal

    2013-01-01

    Haloarchaea are the predominant microflora of hypersaline econiches such as solar salterns, soda lakes, and estuaries where the salinity ranges from 35 to 400 ppt. Econiches like estuaries and solar crystallizer ponds may contain high concentrations of metals since they serve as ecological sinks for metal pollution and also as effective traps for river borne metals. The availability of metals in these econiches is determined by the type of metal complexes formed and the solubility of the metal species at such high salinity. Haloarchaea have developed specialized mechanisms for the uptake of metals required for various key physiological processes and are not readily available at high salinity, beside evolving resistance mechanisms for metals with high solubility. The present paper seeks to give an overview of the main molecular mechanisms involved in metal tolerance in haloarchaea and focuses on factors such as salinity and metal speciation that affect the bioavailability of metals to haloarchaea. Global transcriptomic analysis during metal stress in these organisms will help in determining the various factors differentially regulated and essential for metal physiology. PMID:23533331

  8. Mechanisms of metal resistance and homeostasis in haloarchaea.

    Science.gov (United States)

    Srivastava, Pallavee; Kowshik, Meenal

    2013-01-01

    Haloarchaea are the predominant microflora of hypersaline econiches such as solar salterns, soda lakes, and estuaries where the salinity ranges from 35 to 400 ppt. Econiches like estuaries and solar crystallizer ponds may contain high concentrations of metals since they serve as ecological sinks for metal pollution and also as effective traps for river borne metals. The availability of metals in these econiches is determined by the type of metal complexes formed and the solubility of the metal species at such high salinity. Haloarchaea have developed specialized mechanisms for the uptake of metals required for various key physiological processes and are not readily available at high salinity, beside evolving resistance mechanisms for metals with high solubility. The present paper seeks to give an overview of the main molecular mechanisms involved in metal tolerance in haloarchaea and focuses on factors such as salinity and metal speciation that affect the bioavailability of metals to haloarchaea. Global transcriptomic analysis during metal stress in these organisms will help in determining the various factors differentially regulated and essential for metal physiology.

  9. Mechanisms of Metal Resistance and Homeostasis in Haloarchaea

    Directory of Open Access Journals (Sweden)

    Pallavee Srivastava

    2013-01-01

    Full Text Available Haloarchaea are the predominant microflora of hypersaline econiches such as solar salterns, soda lakes, and estuaries where the salinity ranges from 35 to 400 ppt. Econiches like estuaries and solar crystallizer ponds may contain high concentrations of metals since they serve as ecological sinks for metal pollution and also as effective traps for river borne metals. The availability of metals in these econiches is determined by the type of metal complexes formed and the solubility of the metal species at such high salinity. Haloarchaea have developed specialized mechanisms for the uptake of metals required for various key physiological processes and are not readily available at high salinity, beside evolving resistance mechanisms for metals with high solubility. The present paper seeks to give an overview of the main molecular mechanisms involved in metal tolerance in haloarchaea and focuses on factors such as salinity and metal speciation that affect the bioavailability of metals to haloarchaea. Global transcriptomic analysis during metal stress in these organisms will help in determining the various factors differentially regulated and essential for metal physiology.

  10. Activity of ceftazidime-avibactam against multidrug-resistance Enterobacteriaceae expressing combined mechanisms of resistance.

    Science.gov (United States)

    López-Hernández, Inmaculada; Alonso, Noemí; Fernández-Martínez, Marta; Zamorano, Laura; Rivera, Alba; Oliver, Antonio; Conejo, M Carmen; Martínez-Martínez, Luis; Navarro, Ferrán; Pascual, Alvaro

    2017-10-01

    Antimicrobial resistance in Enterobacteriaceae is increasing worldwide and is making treating infections caused by multidrug-resistant Enterobacteriaceae a challenge. The use of β-lactam agents is compromised by microorganisms harboring extended-spectrum β-lactamases (ESBLs) and other mechanisms of resistance. Avibactam is a non β-lactam agent that inhibits clinically relevant β-lactamases, such as ESBL and AmpC. The ceftazidime-avibactam combination (CAZ-AVI) was recently approved for use in certain complicated infections, and may provide a therapeutic alternative for infections caused by these microorganisms. The in vitro activity of CAZ and CAZ-AVI (AVI at a fixed concentration of 4mg/L) was tested against 250 clinical isolates of Enterobacteriaceae using broth microdilution. EUCAST breakpoint criteria were used for CAZ, and FDA criteria for CAZ-AVI. Clinical isolates included bacteria producing extended-spectrum β-lactamases (ESBLs) and acquired AmpC β-lactamases (AACBLs). Porin loss in Klebsiella pneumoniae was also evaluated. The combination of AVI with CAZ displayed excellent activity against clinical isolates of ESBL-producing Escherichia coli and Klebsiella pneumoniae, rendering all the ceftazidime-resistant isolates susceptible to ceftazidime. CAZ-AVI retained activity against porin-deficient isolates of K. pneumoniae producing ESBLs, AACBLs, or both, although MIC values were higher compared to porin-expressing isolates. CAZ-AVI rendered all the ceftazidime-resistant AACBL-producing Enterobacteriaceae tested susceptible to ceftazidime. CAZ-AVI showed potent in vitro activity against clinical isolates of Enterobacteriaceae producing ESBLs and/or AACBLs, including K. pneumoniae with loss of porins. Copyright © 2016 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  11. Low Prevalence of Carbapenem-Resistant Bacteria in River Water: Resistance Is Mostly Related to Intrinsic Mechanisms.

    Science.gov (United States)

    Tacão, Marta; Correia, António; Henriques, Isabel S

    2015-10-01

    Carbapenems are last-resort antibiotics to handle serious infections caused by multiresistant bacteria. The incidence of resistance to these antibiotics has been increasing and new resistance mechanisms have emerged. The dissemination of carbapenem resistance in the environment has been overlooked. The main goal of this research was to assess the prevalence and diversity of carbapenem-resistant bacteria in riverine ecosystems. The presence of frequently reported carbapenemase-encoding genes was inspected. The proportion of imipenem-resistant bacteria was on average 2.24 CFU/ml. Imipenem-resistant strains (n=110) were identified as Pseudomonas spp., Stenotrophomonas maltophilia, Aeromonas spp., Chromobacterium haemolyticum, Shewanella xiamenensis, and members of Enterobacteriaceae. Carbapenem-resistant bacteria were highly resistant to other beta-lactams such as quinolones, aminoglycosides, chloramphenicol, tetracyclines, and sulfamethoxazole/trimethoprim. Carbapenem resistance was mostly associated with intrinsically resistant bacteria. As intrinsic resistance mechanisms, we have identified the blaCphA gene in 77.3% of Aeromonas spp., blaL1 in all S. maltophilia, and blaOXA-48-like in all S. xiamenensis. As acquired resistance mechanisms, we have detected the blaVIM-2 gene in six Pseudomonas spp. (5.45%). Integrons with gene cassettes encoding resistance to aminoglycosides (aacA and aacC genes), trimethoprim (dfrB1b), and carbapenems (blaVIM-2) were found in Pseudomonas spp. Results suggest that carbapenem resistance dissemination in riverine ecosystems is still at an early stage. Nevertheless, monitoring these aquatic compartments for the presence of resistance genes and its host organisms is essential to outline strategies to minimize resistance dissemination.

  12. An in vitro investigation of a newer intracanal medicament Nisin on Enterococcus faecalis in comparison with chlorhexidine and calcium hydroxide

    Directory of Open Access Journals (Sweden)

    Suneel Kumar Chinni

    2011-01-01

    Full Text Available Aim: To determine the antibacterial efficacy of Nisin in comparison with Calcium hydroxide and Chlorhexidine. Materials and Methods: Fifty extracted lower premolar single-rooted teeth were collected and were instrumented with K3 rotary files. Then, root canals were inoculated with a bacterial solution of Enterococcus faecalis. After 21 days, the canals were inoculated with Saline, Nisin, Vancomycin, Calcium hydroxide, and Chlorhexidine. The roots were left for 7 days and on the 8 th day, to investigate the degree of infection of the radicular dentin, specimens of the dentin chips from the full length of the root canal were harvested using a sterile rotary K3 instrument (size 25 6% taper. Results: The results of the present study showed that Nisin and Chlorhexidine showed none of Colony Forming Units (CFU in their respective group. Conclusion: Within the limits of the study, Nisin was effective in eradicating E. faecalis cells in pure culture and root canal dentin.

  13. Life cycle synchronization is a viral drug resistance mechanism.

    Directory of Open Access Journals (Sweden)

    Iulia A Neagu

    2018-02-01

    Full Text Available Viral infections are one of the major causes of death worldwide, with HIV infection alone resulting in over 1.2 million casualties per year. Antiviral drugs are now being administered for a variety of viral infections, including HIV, hepatitis B and C, and influenza. These therapies target a specific phase of the virus's life cycle, yet their ultimate success depends on a variety of factors, such as adherence to a prescribed regimen and the emergence of viral drug resistance. The epidemiology and evolution of drug resistance have been extensively characterized, and it is generally assumed that drug resistance arises from mutations that alter the virus's susceptibility to the direct action of the drug. In this paper, we consider the possibility that a virus population can evolve towards synchronizing its life cycle with the pattern of drug therapy. The periodicity of the drug treatment could then allow for a virus strain whose life cycle length is a multiple of the dosing interval to replicate only when the concentration of the drug is lowest. This process, referred to as "drug tolerance by synchronization", could allow the virus population to maximize its overall fitness without having to alter drug binding or complete its life cycle in the drug's presence. We use mathematical models and stochastic simulations to show that life cycle synchronization can indeed be a mechanism of viral drug tolerance. We show that this effect is more likely to occur when the variability in both viral life cycle and drug dose timing are low. More generally, we find that in the presence of periodic drug levels, time-averaged calculations of viral fitness do not accurately predict drug levels needed to eradicate infection, even if there is no synchronization. We derive an analytical expression for viral fitness that is sufficient to explain the drug-pattern-dependent survival of strains with any life cycle length. We discuss the implications of these findings for

  14. Wear resistance and fracture mechanics of WC-Co composites

    Energy Technology Data Exchange (ETDEWEB)

    Kaytbay, Saleh [Benha Univ. (Egypt). Dept. of Mechanical Engineering; El-Hadek, Medhat [Port-Said Univ. (Egypt). Dept. of Production and Mechanical Design

    2014-06-15

    Manufacturing of WC-Co composites using the electroless precipitation method at different sintering temperatures of 1 100, 1 250, 1 350 and 1 500 C was successfully achieved. The chemical composition of the investigated materials was 90 wt.% WC with 10 wt.% Co, and 80 wt.% WC with 20 wt.% Co. The specific density, densification, and Vickers microhardness measurements were found to increase with increased sintering temperature for both the WC-Co compositions. The composites of tungsten carbide with 10 wt.% Co had a higher specific density and Vickers microhardness measurements than those for the composites of tungsten carbide with 20 wt.% Co. Composites with WC-10 wt.% Co had better wear resistance. The stress-strain and transverse rupture strength increased monotonically with the increase in sintering temperatures, agreeing with the material hardness and wear resistance behavior. Fractographical scanning electron microscopy analysis of the fracture surface demonstrated a rough characteristic conical shape failure in the direction of the maximum shear stress. A proposed mechanism for the formation of the conical fracture surface under compression testing is presented. (orig.)

  15. Mutational and acquired carbapenem resistance mechanisms in multidrug resistant Pseudomonas aeruginosa clinical isolates from Recife, Brazil.

    Science.gov (United States)

    Cavalcanti, Felipe Lira de Sá; Mirones, Cristina Rodríguez; Paucar, Elena Román; Montes, Laura Álvarez; Leal-Balbino, Tereza Cristina; Morais, Marcia Maria Camargo de; Martínez-Martínez, Luis; Ocampo-Sosa, Alain Antonio

    2015-12-01

    An investigation was carried out into the genetic mechanisms responsible for multidrug resistance in nine carbapenem-resistant Pseudomonas aeruginosa isolates from different hospitals in Recife, Brazil. Susceptibility to antimicrobial agents was determined by broth microdilution. Polymerase chain reaction (PCR) was employed to detect the presence of genes encoding β-lactamases, aminoglycoside-modifying enzymes (AMEs), 16S rRNA methylases, integron-related genes and OprD. Expression of genes coding for efflux pumps and AmpC cephalosporinase were assessed by quantitative PCR. The outer membrane proteins were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The blaSPM-1, blaKPC-2 and blaGES-1 genes were detected in P. aeruginosa isolates in addition to different AME genes. The loss of OprD in nine isolates was mainly due to frameshift mutations, premature stop codons and point mutations. An association of loss of OprD with the overexpression of MexAB-OprM and MexXY-OprM was observed in most isolates. Hyper-production of AmpC was also observed in three isolates. Clonal relationship of the isolates was determined by repetitive element palindromic-PCR and multilocus sequence typing. Our results show that the loss of OprD along with overexpression of efflux pumps and β-lactamase production were responsible for the multidrug resistance in the isolates analysed.

  16. Mechanisms of resistance and cross-resistance to agrochemicals in the fairy shrimp Thamnocephalus platyurus (Crustacea: Anostraca).

    Science.gov (United States)

    Brausch, John M; Smith, Philip N

    2009-05-05

    Extensive pesticide usage in the Southern High Plains has led to the development of resistance in many pest species, as well as some non-target organisms. Thamnocephalus platyurus derived from agriculturally impacted watersheds are between two and three times less sensitive to commonly applied agrochemicals than T. platyurus from native grassland watersheds. Biological mechanisms that convey such resistance are currently unknown. This study identified the contribution of metabolic enzymes to T. platyurus pesticide resistance using the synergists piperonyl butoxide (PBO) and S,S,S-tributyl phosphorotrithioate (DEF) to inhibit cytochrome P450s or hydrolases, respectively. Inhibition of cytochrome P450s and hydrolases partially restored cyfluthrin and DDT sensitivity in T. platyurus, suggesting other resistance inferring mechanism(s) were also involved. However, inhibition of hydrolases with DEF completely restored methyl parathion sensitivity in pesticide resistant T. platyurus. DDT resistance paralleled cyfluthrin resistance, but did not for methyl parathion resistance. These data suggest that the primary mechanism for the development of resistance to agrochemicals in T. platyurus is due to increased metabolic detoxification.

  17. Biochemical Mechanism of HIV-1 Resistance to Rilpivirine*

    Science.gov (United States)

    Singh, Kamalendra; Marchand, Bruno; Rai, Devendra K.; Sharma, Bechan; Michailidis, Eleftherios; Ryan, Emily M.; Matzek, Kayla B.; Leslie, Maxwell D.; Hagedorn, Ariel N.; Li, Zhe; Norden, Pieter R.; Hachiya, Atsuko; Parniak, Michael A.; Xu, Hong-Tao; Wainberg, Mark A.; Sarafianos, Stefan G.

    2012-01-01

    Rilpivirine (RPV) is a second generation nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) that efficiently inhibits HIV-1 resistant to first generation NNRTIs. Virological failure during therapy with RPV and emtricitabine is associated with the appearance of E138K and M184I mutations in RT. Here we investigate the biochemical mechanism of RT inhibition and resistance to RPV. We used two transient kinetics approaches (quench-flow and stopped-flow) to determine how subunit-specific mutations in RT p66 or p51 affect association and dissociation of RPV to RT as well as their impact on binding of dNTP and DNA and the catalytic incorporation of nucleotide. We compared WT with four subunit-specific RT mutants, p66M184I/p51WT, p66E138K/p51E138K, p66E138K/M184I/p51E138K, and p66M184I/p51E138K. Ile-184 in p66 (p66184I) decreased the catalytic efficiency of RT (kpol/Kd.dNTP), primarily through a decrease in dNTP binding (Kd.dNTP). Lys-138 either in both subunits or in p51 alone abrogated the negative effect of p66184I by restoring dNTP binding. Furthermore, p51138K reduced RPV susceptibility by altering the ratio of RPV dissociation to RPV association, resulting in a net reduction in RPV equilibrium binding affinity (Kd.RPV = koff.RPV/kon.RPV). Quantum mechanics/molecular mechanics hybrid molecular modeling revealed that p51E138K affects access to the RPV binding site by disrupting the salt bridge between p51E138 and p66K101. p66184I caused repositioning of the Tyr-183 active site residue and decreased the efficiency of RT, whereas the addition of p51138K restored Tyr-183 to a WT-like conformation, thus abrogating the Ile-184-induced functional defects. PMID:22955279

  18. Biochemical mechanism of HIV-1 resistance to rilpivirine.

    Science.gov (United States)

    Singh, Kamalendra; Marchand, Bruno; Rai, Devendra K; Sharma, Bechan; Michailidis, Eleftherios; Ryan, Emily M; Matzek, Kayla B; Leslie, Maxwell D; Hagedorn, Ariel N; Li, Zhe; Norden, Pieter R; Hachiya, Atsuko; Parniak, Michael A; Xu, Hong-Tao; Wainberg, Mark A; Sarafianos, Stefan G

    2012-11-02

    Rilpivirine (RPV) is a second generation nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) that efficiently inhibits HIV-1 resistant to first generation NNRTIs. Virological failure during therapy with RPV and emtricitabine is associated with the appearance of E138K and M184I mutations in RT. Here we investigate the biochemical mechanism of RT inhibition and resistance to RPV. We used two transient kinetics approaches (quench-flow and stopped-flow) to determine how subunit-specific mutations in RT p66 or p51 affect association and dissociation of RPV to RT as well as their impact on binding of dNTP and DNA and the catalytic incorporation of nucleotide. We compared WT with four subunit-specific RT mutants, p66(M184I)/p51(WT), p66(E138K)/p51(E138K), p66(E138K/M184I)/p51(E138K), and p66(M184I)/p51(E138K). Ile-184 in p66 (p66(184I)) decreased the catalytic efficiency of RT (k(pol)/K(d)(.dNTP)), primarily through a decrease in dNTP binding (K(d)(.dNTP)). Lys-138 either in both subunits or in p51 alone abrogated the negative effect of p66(184I) by restoring dNTP binding. Furthermore, p51(138K) reduced RPV susceptibility by altering the ratio of RPV dissociation to RPV association, resulting in a net reduction in RPV equilibrium binding affinity (K(d)(.RPV) = k(off.RPV)/k(on.RPV)). Quantum mechanics/molecular mechanics hybrid molecular modeling revealed that p51(E138K) affects access to the RPV binding site by disrupting the salt bridge between p51(E138) and p66(K101). p66(184I) caused repositioning of the Tyr-183 active site residue and decreased the efficiency of RT, whereas the addition of p51(138K) restored Tyr-183 to a WT-like conformation, thus abrogating the Ile-184-induced functional defects.

  19. Rapid dissemination of colistin and carbapenem resistant Acinetobacter baumannii in Central Greece: mechanisms of resistance, molecular identification and epidemiological data.

    Science.gov (United States)

    Oikonomou, O; Sarrou, S; Papagiannitsis, C C; Georgiadou, S; Mantzarlis, K; Zakynthinos, E; Dalekos, G N; Petinaki, E

    2015-12-09

    Colistin-resistant/carbapenem-resistant Acinetobacter baumannii is a significant challenge for antibiotic treatment and infection control policies. Since 2012, in Central Greece an increase of colistin/pan- resistant A. baumannii has occurred, indicating the need for further analysis. A total of 86 colistin-resistant/carbapenem-resistant out of 1228 A. baumannii clinical isolates, consecutively collected between 2012 and 2014 in a tertiary Greek hospital of Central Greece, as well as one environmental isolate from surveillance cultures were studied. Molecular typing and mechanisms of resistance to colistin and to carbapenems were assessed, whereas, epidemiological and clinical data of the patients were reviewed. During the study period, the rate of colistin resistance gradually increased and reached 21.1 % in 2014. All colistin-resistant/carbapenem-resistant A. baumannii belonged to 3LST ST101 clone that corresponds to the international clonal lineage II. Carbapenem resistance was associated with the presence of bla oxa-23-like, while resistance to colistin probably correlated with G54E and R109H amino acid substitutions in PmrA and PmrC, respectively. Epidemiological data of the patients indicated that the first detection of colistin-resistant/carbapenem-resistant ST101 clone in the University Hospital of Larissa (UHL) was associated with a patient who previously had received colistin, while, the movement of the infected patients into the hospital probably resulted to its spread.

  20. Characterization of resistance mechanisms to powdery mildew (Erysiphe betae) in beet (Beta vulgaris).

    Science.gov (United States)

    Fernández-Aparicio, Mónica; Prats, Elena; Emeran, Amero A; Rubiales, Diego

    2009-04-01

    Beet powdery mildew incited by Erysiphe betae is a serious foliar fungal disease of worldwide distribution causing losses of up to 30%. In the present work, we searched for resistance in a germplasm collection of 184 genotypes of Beta vulgaris including fodder (51 genotypes), garden (60 genotypes), leaf (51 genotypes), and sugar (22 genotypes) beet types. Resistant genotypes were identified in the four beet types under study. In addition, mechanisms underlying resistance were dissected through histological studies. These revealed different resistance mechanisms acting at different fungal developmental stages, i.e., penetration resistance, early and late cell death, or posthaustorial resistance. Most genotypes were able to hamper fungal development at several stages. The later are interesting for breeding aiming to resistance durability. Furthermore, characterization of defense mechanisms will be useful for further cellular and molecular studies to unravel the bases of resistance in this species.

  1. Experimental Induction of Bacterial Resistance to the Antimicrobial Peptide Tachyplesin I and Investigation of the Resistance Mechanisms.

    Science.gov (United States)

    Hong, Jun; Hu, Jianye; Ke, Fei

    2016-10-01

    Tachyplesin I is a 17-amino-acid cationic antimicrobial peptide (AMP) with a typical cyclic antiparallel β-sheet structure that is a promising therapeutic for infections, tumors, and viruses. To date, no bacterial resistance to tachyplesin I has been reported. To explore the safety of tachyplesin I as an antibacterial drug for wide clinical application, we experimentally induced bacterial resistance to tachyplesin I by using two selection procedures and studied the preliminary resistance mechanisms. Aeromonas hydrophila XS91-4-1, Pseudomonas aeruginosa CGMCC1.2620, and Escherichia coli ATCC 25922 and F41 showed resistance to tachyplesin I under long-term selection pressure with continuously increasing concentrations of tachyplesin I. In addition, P. aeruginosa and E. coli exhibited resistance to tachyplesin I under UV mutagenesis selection conditions. Cell growth and colony morphology were slightly different between control strains and strains with induced resistance. Cross-resistance to tachyplesin I and antimicrobial agents (cefoperazone and amikacin) or other AMPs (pexiganan, tachyplesin III, and polyphemusin I) was observed in some resistant mutants. Previous studies showed that extracellular protease-mediated degradation of AMPs induced bacterial resistance to AMPs. Our results indicated that the resistance mechanism of P. aeruginosa was not entirely dependent on extracellular proteolytic degradation of tachyplesin I; however, tachyplesin I could induce increased proteolytic activity in P. aeruginosa Most importantly, our findings raise serious concerns about the long-term risks associated with the development and clinical use of tachyplesin I. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Origin and evolution of antibiotic resistance: the common mechanisms of emergence and spread in water bodies

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    Agnese eLupo

    2012-01-01

    Full Text Available The environment, and especially fresh water, constitutes a reactor where the evolution and the rise of new resistances occur. In rivers or streams, bacteria from different sources such as urban, industrial and agricultural waste, probably selected by intensive antibiotic usage, are collected and mixed with environmental species. This may cause two effects on the development of antibiotic resistances: First, the contamination of water by antibiotics or other pollutants lead to the rise of resistance due to selection processes. For instance, of strains over-expressing broad range defensive mechanisms, such as efflux pumps. Second, since environmental species are provided with intrinsic antibiotic resistance mechanisms, the mixture with allochthonous species is likely to cause genetic exchange. In this context, the role of phages and integrons for the spread of resistance mechanisms appears significant. Allochthonous species could acquire new resistances from environmental donors and introduce the newly acquired resistance mechanisms into the clinics. This is illustrated by clinically relevant resistance mechanisms, such as the fluoroquinolones resistance genes qnr. Freshwater appears to play an important role in the emergence and in the spread of antibiotic resistances, highlighting the necessity for strategies of water quality improvement. Moreover, further knowledge is needed to better understand the role of the environment as reservoir of antibiotic resistances and to assess the risk of spread of antibiotic resistances via water bodies.

  3. Understanding cellular responses to toxic agents: a model for mechanism-choice in bacterial metal resistance.

    Science.gov (United States)

    Rouch, D A; Lee, B T; Morby, A P

    1995-02-01

    Bacterial resistances to metals are heterogeneous in both their genetic and biochemical bases. Metal resistance may be chromosomally-, plasmid- or transposon-encoded, and one or more genes may be involved: at the biochemical level at least six different mechanisms are responsible for resistance. Various types of resistance mechanisms can occur singly or in combination and for a particular metal different mechanisms of resistance can occur in the same species. To understand better the diverse responses of bacteria to metal ion challenge we have constructed a qualitative model for the selection of metal resistance in bacteria. How a bacterium becomes resistant to a particular metal depends on the number and location of cellular components sensitive to the specific metal ion. Other important selective factors include the nature of the uptake systems for the metal, the role and interactions of the metal in the normal metabolism of the cell and the availability of plasmid (or transposon) encoded resistance mechanisms. The selection model presented is based on the interaction of these factors and allows predictions to be made about the evolution of metal resistance in bacterial populations. It also allows prediction of the genetic basis and of mechanisms of resistance which are in substantial agreement with those in well-documented populations. The interaction of, and selection for resistance to, toxic substances in addition to metals, such as antibiotics and toxic analogues, involve similar principles to those concerning metals. Potentially, models for selection of resistance to any substance can be derived using this approach.

  4. Clinical epidemiology and resistance mechanisms of carbapenem-resistant Acinetobacter baumannii, French Guiana, 2008-2014.

    Science.gov (United States)

    Mahamat, Aba; Bertrand, Xavier; Moreau, Brigitte; Hommel, Didier; Couppie, Pierre; Simonnet, Christine; Kallel, Hatem; Demar, Magalie; Djossou, Felix; Nacher, Mathieu

    2016-07-01

    This study investigated the clinical epidemiology and resistance mechanisms of Acinetobacter baumannii and characterised the clonal diversity of carbapenem-resistant A. baumannii (CRAB) during an ICU-associated outbreak at Cayenne Hospital, French Guiana. All non-duplicate A. baumannii isolates from 2008 to 2014 were tested for antibiotic susceptibility by disk diffusion. Multilocus sequence typing, pulsed-field gel electrophoresis (PFGE) and characterisation of carbapenemase-encoding genes were performed on CRAB. Of the 441 A. baumannii isolates, most were from males (54.0%) and were detected mainly from the ICU (30.8%) and medicine wards (21.8%). In the ICU, strains were mainly isolated from the respiratory tract (44.1%) and bloodstream (14.0%), whereas in medicine wards they mainly were from wound/drainage (36.5%) and bloodstream (25.0%). A. baumannii showed the greatest susceptibility to piperacillin/tazobactam (92.7%), imipenem (92.5%), colistin (95.6%) and amikacin (97.2%), being lower in the ICU and medicine wards compared with other wards. An outbreak of OXA-23-producing CRAB occurred in the 13-bed ICU in 2010. CRAB strains were more co-resistant to other antimicrobials compared with non-CRAB. Molecular genetics analysis revealed five sequence types [ST78, ST107 and ST642 and two new STs (ST830 and ST831)]. Analysis of PFGE profiles indicated cross-transmissions of CRAB within the ICU, between the ICU and one medicine ward during transfer of patients, and within that medicine ward. This study provides the first clinical and molecular data of A. baumannii from French Guiana and the Amazon basin. The ICU was the highest risk unit of this nosocomial outbreak of OXA-23-producing CRAB, which could subsequently disseminate within the hospital. Copyright © 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.

  5. Molluscicidal activities of curcumin-nisin polylactic acid nanoparticle on Biomphalaria pfeifferi.

    Directory of Open Access Journals (Sweden)

    Michael E Omobhude

    2017-08-01

    Full Text Available Snail intermediate host control is a widely canvassed strategy for schistosomiasis control in endemic countries. While there have been increasing studies on the search for potent molluscicides in the past years, the use of nanoparticulate agents as molluscicides is yet to gain wide attention. The aim of this study was to assess the molluscicidal potential of curcumin-nisin poly lactic acid (PLA entrapped nanoparticle (CurNisNp against Biomphalaria pfeifferi, a snail intermediate host for Schistosoma mansoni.CurNisNp formulated by double emulsion method was tested against the young adults, < 1 week, 1-2-week old juveniles, 1 day (blastula and 7 day-old (hippo-stage egg masses of B. pfeifferi. Mortality in the different stages was determined after 96-h of exposure at varying concentrations (350, 175, 87.5, 43.75 and 21.88 ppm. The sub-lethal effects of CurNisNp on the hatchability of the 7-day-old egg masses and egg laying capacity of the young adult snails were determined. The CurNisNp diameter, polydispersity index (PDI, zeta potential and drug entrapment efficiency were 284.0 ± 17.9 nm, 0.166 ± 0.03, -16.6 ± 2.45 mV and 35.0% respectively. The < 1 week old juveniles and the 1-day-old egg stage (blastula of B. pfeifferi with LC50 277.9 ppm and 4279.5 ppm were the most susceptible and resistant stages to the drug respectively. CurNisNp was also observed to cause significant reductions (P<0.05 in egg hatchability and egg laying capacity with strong negative correlation between egg laying capacity and concentration (r = -0.928; P<0.05.This study showed that CurNisNp has molluscicidal activities on different developmental stages of B. pfeifferi. It is therefore recommended that the formulation be more optimised to give a nanoparticle with a narrow range monodispersed PDI for better drug distribution and eventual greater molluscicidal activities.

  6. Antimicrobial activity optimization of nisin, ascorbic acid and ethylenediamine tetraacetic acid disodium salt (EDTA against Salmonella Enteritidis ATCC 13076 using response surface methodology

    Directory of Open Access Journals (Sweden)

    Nongpanga Sangcharoen

    2017-10-01

    Full Text Available Nisin is a commercial bacteriocin produced by Lactococcus lactis subsp. lactis and widely used as a natural preservative in the food industry. However, while nisin alone cannot inhibit the growth of Gram-negative bacteria, it can in combination with a chelating agent or organic acid. This study combined nisin with some chelating agents, weak organic acids and their salts to inhibit Salmonella Enteritidis ATCC 13076. The combinations of nisin (2000 parts per million; ppm and ascorbic acid (2000 ppm or ethylenediamine tetraacetic acid disodium salt (EDTA; 7400 ppm showed significant inhibitory effects on the target strain. Due to regulatory limits, the second part of the study reduced the concentrations of nisin, ascorbic acid and EDTA to 500 ppm, 2000 ppm and 250 ppm, respectively. The mixture of nisin, ascorbic acid and EDTA showed the highest inhibitory effect with a reduction number of 3.41 log colony forming units (p < 0.05. To minimize the growth of S. Enteritidis ATCC 13076, central composite design and response surface methodology were applied to investigate the combined effect of nisin (0–500 ppm, ascorbic acid (0–2000 ppm, and EDTA (0–250 ppm on the target strain growth. Among the three factors, nisin had a higher antimicrobial effect than ascorbic acid or EDTA, while an increase in nisin resulted in a decrease in S. Enteritidis ATCC 13076 growth. The optimum concentration was 500 ppm nisin with 1515 ppm ascorbic acid and 250 ppm EDTA. Under these conditions, the growth of S. Enteritidis ATCC 13076 predicted by the model was 24.99%. Keywords: Antimicrobial activity, Ascorbic acid, Ethylenediamine tetraacetic acid disodium salt (EDTA, Nisin, Salmonella enteritidis

  7. Resistance to antivirals in human cytomegalovirus: mechanisms and clinical significance.

    Science.gov (United States)

    Pérez, J L

    1997-09-01

    Long term therapies needed for managing human cytomegalovirus (HCMV) infections in immunosupressed patients provided the background for the emergence of the resistance to antivirals active against HCMV. In addition, laboratory selected mutants have also been readily achieved. Both clinical and laboratory resistant strains share the same determinants of resistance. Ganciclovir resistance may be due to a few mutations in the HCMV UL97 gene and/or viral DNA pol gene, the former being responsible for about 70% of clinical resistant isolates. Among them, V464, V594, S595 and F595 are the most frequent mutations. Because of their less extensive clinical use, much less is known about resistance to foscarnet and cidofovir (formerly, HPMPC) but in both cases, it has been associated to mutations in the DNA pol. Ganciclovir resistant strains showing DNA pol mutations are cross-resistant to cidofovir and their corresponding IC50 are normally higher than those from strains harboring only mutations at the UL97 gene. To date, foscarnet resistance seems to be independent of both ganciclovir and cidofovir resistance.

  8. Investigating of four main carbapenem-resistance mechanisms in high-level carbapenem resistant Pseudomonas aeruginosa isolated from burn patients

    Directory of Open Access Journals (Sweden)

    Soodabeh Rostami

    2018-02-01

    Conclusion: Emerging antimicrobial resistance in burn wound bacterial pathogens is a serious therapeutic challenge for clinicians. In the present study, most of the isolates were MDR. This finding indicated an alarming spread of resistant isolates and suggested that infection control strategies should be considered. Resistance to carbapenems is influenced by several factors, not all of which were evaluated in our study; however, the results showed that production of MBLs and overexpression of the mexB gene were the most frequent mechanisms in carbapenem-resistant isolates.

  9. Innovative bionanocomposite films of edible proteins containing liposome-encapsulated nisin and halloysite nanoclay.

    Science.gov (United States)

    Boelter, Juliana Ferreira; Brandelli, Adriano

    2016-09-01

    Films and coatings based on natural polymers have gained increased interest for food packaging applications. In this work, halloysite and phosphatidylcholine liposomes encapsulating nisin were used to develop nanocomposite films of gelatin and casein. Liposomes prepared with either soybean lecithin or Phospholipon(®) showed particle size ranging from 124 to 178nm and high entrapment efficiency (94-100%). Considering their stability, Phospholipon(®) liposomes with 1.0mg/ml nisin were selected for incorporation into nanocomposite films containing 0.5g/l halloysite. The films presented antimicrobial activity against Listeria monocytogenes, Clostridium perfringens and Bacillus cereus. Scanning electron microscopy revealed that the films had a smooth surface, but showed increased roughness with addition of liposomes and halloysite. Casein films were thinner and slightly yellowish, less rigid and very elastic as compared with gelatin films. Thermogravimetric analysis showed a decrease of the degradation temperature for casein films added with liposomes. The glass transition temperature decreased with addition of liposomes and halloysite. Gelatin and casein films containing nisin-loaded liposomes and halloysite represent an interesting alternative for development of active food packaging. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Core-shell PLA-PVA porous microparticles as carriers for bacteriocin nisin.

    Science.gov (United States)

    Holcapkova, Pavlina; Hrabalikova, Martina; Stoplova, Petra; Sedlarik, Vladimir

    2017-05-01

    This work is focused on preparation of novel porous type of core-shell-structured microparticles based on polylactide (shell) and poly(vinyl alcohol) cross-linked with glutaric acid (GA) (core) prepared by water-in-oil-in-water solvent evaporation technique. The microparticle systems were used as delivery systems for immobilisation of model antibacterial agent - nisin. The effect of cross-linking and the initial amount of nisin on their morphology was investigated using scanning electron microscopy, BET analysis, zeta potential measurement and Fourier transform infra-red spectroscopy. Encapsulation efficiency and release profile of nisin from the microparticles were studied by high performance liquid chromatography. Antibacterial activity of the prepared systems was tested by dilution and spread plate technique. Results showed the microparticles in the size range of 9-16 μm in diameter with spherical multi-hollow core-shell structure. The presence of cross-linking agent GA influences the release profile of the peptide and has synergistic effect on Listeria monocytogenes growth reduction.

  11. Effect of ionization and nisin on the Bacillus strains and Salmonella Enteritidis inoculated Stearothermophilus

    International Nuclear Information System (INIS)

    Bouzayen, Sarra

    2010-01-01

    The antimicrobial effect of nisin (at 1000UI/g), and irradiation (at 1, 3 and 5kGy), against the growth of Salmonella enteritidis (106 ufc/ml) and Bacillus Stearothermophilus (10 6 ufc/ml), inoculated in turkey salami, was studied during storage at 4 degree for 21 days. Treatment of turkey salami with nisin at 1000UI/g did not show any antimicrobial activity against S. Enteritidis with 6.7 pour cent and 0.8 pour cent of reduction after 0 and 21 days of storage respectively, and seems to be insufficient to inhibit B. Stearothermophilus with 23 pour cent and 21 pour cent of reduction after 0 and 21 days of storage respectively. Antimicrobial activities of irradiation were better and proportional to irradiation doses; it shows a reduction of 27 pour cent, 55 pour cent and 67 pour cent by D1, D2 and D3 respectively. The combination of nisin with irradiation at 5kGy showed stronger antimicrobial activities than those obtained by its combination with the first and the second irradiation dose.

  12. Inhibition of Listeria monocytogenes on cold-smoked salmon by nisin and carbon dioxide atmosphere

    DEFF Research Database (Denmark)

    Nilsson, Lilian; Huss, Hans Henrik; Gram, Lone

    1997-01-01

    concentration less than or equal to 50 IU/ml resulted in the survival and growth of L. monocytogenes in all combinations with other preservatives (NaCl, CO2). Addition of nisin (500 or 1000 IU/g) to cold-smoked salmon inoculated with L. monocytogenes and stored at 5 degrees C delayed, but did not prevent growth......The bacteriostatic and bacteriocidal effect of nisin in combination with carbon dioxide, NaCl and low temperature on the survival of Listeria monocytogenes was investigated in in vitro model studies and in trials with cold-smoked salmon. Addition of nisin caused various degrees of inhibition...... of L. monocytogenes in vacuum-packs. Numbers of L. monocytogenes increased to 10(8) cfu/g in vacuum packed cold-smoked salmon in 8 days, whereas CO2 packing of cold- smoked salmon resulted in an 8-day lag phase of L. monocytogenes, with numbers eventually reaching 10(6) cfu/g in 27 days. Addition...

  13. Genetic resistance in experimental autoimmune encephalomyelitis. I. Analysis of the mechanism of LeR resistance using radiation chimeras

    International Nuclear Information System (INIS)

    Pelfrey, C.M.; Waxman, F.J.; Whitacre, C.C.

    1989-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a cell-mediated autoimmune disease of the central nervous system that has been extensively studied in the rat. The Lewis rat is highly susceptible to the induction of EAE, while the Lewis resistant (LeR) rat is known to be resistant. In this paper, we demonstrate that the LeR rat, which was derived from the Lewis strain by inbreeding of fully resistant animals, is histocompatible with the Lewis strain. Radiation chimeras, a tool for distinguishing between immunologic and nonimmunologic resistance mechanisms, were utilized to analyze the cellular mechanisms involved in genetic resistance to EAE. By transplanting bone marrow cells from LeR rats into irradiated Lewis recipients, Lewis rats were rendered resistant to EAE induction. Likewise, transplanting Lewis bone marrow cells into irradiated LeR recipients rendered LeR rats susceptible. Mixed lymphoid cell chimeras using bone marrow, spleen, and thymus cells in Lewis recipient rats revealed individual lymphoid cell types and cell interactions that significantly affected the incidence and severity of EAE. Our results suggest that LeR resistance is mediated by hematopoietic/immune cells, and that cells located in the spleen appear to play a critical role in the resistance/susceptibility to EAE induction. Depletion of splenic adherent cells did not change the patterns of EAE resistance. In vivo cell mixing studies suggested the presence of a suppressor cell population in the LeR spleen preparations which exerted an inhibitory effect on Lewis autoimmune responses. Thus, the mechanism of LeR resistance appears to be different from that in other EAE-resistant animals

  14. Characterization of Pseudomonas aeruginosa isolates from dogs and cats in Japan: current status of antimicrobial resistance and prevailing resistance mechanisms.

    Science.gov (United States)

    Harada, Kazuki; Arima, Sayuri; Niina, Ayaka; Kataoka, Yasushi; Takahashi, Toshio

    2012-02-01

    Seventy-three Pseudomonas aeruginosa isolates were collected from dogs and cats in Japan to investigate antimicrobial susceptibility and resistance mechanisms to anti-pseudomonal agents. Resistance rates against orbifloxacin, enrofloxacin, ciprofloxacin, cefotaxime, aztreonam and gentamicin were 34.2, 31.5, 20.5, 17.8, 12.3 and 4.1%, respectively. The degree of resistance to cefotaxime, orbifloxacin, and enrofloxacin was greatly affected by efflux pump inhibitors, indicating overexpression of efflux pump contributes to these resistances. Notably, orbifloxacin and enrofloxacin resistance was observed even in isolates without mutations in the target sites. This is the first report on cephalosporin- and fluoroquinolone-resistant isolates of P. aeruginosa from Japanese companion animals. © 2012 The Societies and Blackwell Publishing Asia Pty Ltd.

  15. Genetic resistance to marrow transplantation as a leukemia defense mechanism

    International Nuclear Information System (INIS)

    Gallagher, M.T.; Lotzova, E.; Trentin, J.J.

    1976-01-01

    The normal role of genetic resistance to bone marrow transplantation was investigated. It is demonstrated, using three different systems e.g. colony studies in the spleen, spleen weight studies and mortality studies, that irradiated or unirradiated mice which show genetic resistance are able to recognize and reject intravenously transplanted parental lymphoma cells, while they accept normal parental bone marrow cells. Either the lymphoma cells have a new antigen which is recognized and reacted to by the cells responsible for genetic resistance and, or, bone marrow cells have a low level of Hh antigen which is increased greatly by the lymphoma transformation process, thereby resulting in the rejection of the lymphoma cells by the cells responsible for genetic resistance. Lymphoma resistance as well as genetic resistance can be overridden by increasing the number of cells injected. Genetic resistance seems to be restricted to the spleen and bone marrow. There is evidence that the normal biological role for genetic resistance may be lymphoma-leukemia surveillance

  16. Defense mechanisms involved in disease resistance of grafted vegetables

    Science.gov (United States)

    Vegetable grafting with resistant rootstocks is an effective strategy to control a variety of soil-borne diseases and root-knot nematodes in the Cucurbitaceae and Solanaceae. In addition, improved resistance to some foliar diseases and viruses has also been reported in grafted plants. Hence, graft...

  17. Mechanisms of PGPR-induced resistance against pathogens

    NARCIS (Netherlands)

    Loon, L.C. van; Bakker, P.A.H.M.; Pieterse, C.M.J.

    1997-01-01

    Plant growth-promoting rhizobacteria can suppress diseases through antagonism between the bacteria and soilborne pathogens, as well as by inducing a systemic resistance in the plant against both root and foliar pathogens. Specific Pseudomonas strains induce systemic resistance in carnation,

  18. Stability and Antimicrobial Activity of Nisin-Loaded Mesoporous Silica Nanoparticles: A Game-Changer in the War against Maleficent Microbes

    DEFF Research Database (Denmark)

    Behzadi, Faezeh; Darouie, Sheyda; Alavi, S. Mehdi

    2018-01-01

    Antimicrobial agents, such as nisin, are used extensively in the food industry. Here, we investigated various approaches to load nisin onto mesoporous silica nanoparticles (MSNs, 92 ± 10 nm in diameter), to enhance its stability and sustained release. The morphology, size, and surface charge of t...

  19. Specific binding of nisin to the peptidoglycan precursor lipid II combines pore formation and inhibition of cell wall biosynthesis for potent antibiotic activity

    NARCIS (Netherlands)

    Wiedemann, [No Value; Breukink, E; van Kraaij, C; Kuipers, O.P.; Bierbaum, G; de Kruijff, B; Sahl, HA

    2001-01-01

    Unlike numerous pore-forming amphiphilic peptide antibiotics, the lantibiotic nisin is active in nanomolar concentrations, which results from its ability to use the Lipid-bound cell wall precursor lipid II as a docking molecule for subsequent pore formation. Here we use genetically engineered nisin

  20. Heat-resistant mechanism of transgenic rape by 45Ca isotope tracer

    International Nuclear Information System (INIS)

    Xu Falun; Yang Yuanyou; Liu Ning; Liao Jiali; Yang Jijun; Tang Jun; Liu Zhibin; Yang Yi

    2012-01-01

    The Ca 2+ uptake differences of the rape with heat-resistant gene and the general rape were investigated by 45 Ca isotope tracer. The results showed that the rape with heat-resistant gene can strengthen the regulation of calcium absorption. The calcium regulation ability of the heat-resistant genes may be able to play in the rape aspect of the mechanism of resistance. (authors)

  1. Elucidating the mechanisms of resistance to tyrosine kinase inhibitors in lung cancer patients

    Directory of Open Access Journals (Sweden)

    Asim Joshi

    2017-10-01

    Results: The whole exome data was analyzed using an in-house developed pipeline. Of all the known resistance mutations, we identified EGFR T790M mutation in five out of fifteen patients. Other than T790M we expect to identify novel resistance causing mutations from the analysis of ten patients with unknown resistance mechanisms. Functional validation of these resistance specific alterations would be performed in vitro using drug sensitive lung cancer cell lines.

  2. Telavancin: mechanisms of action, in vitro activity, and mechanisms of resistance.

    Science.gov (United States)

    Karlowsky, James A; Nichol, Kim; Zhanel, George G

    2015-09-15

    Telavancin is a semisynthetic lipoglycopeptide derivative of vancomycin. Telavancin has a dual mechanism of antibacterial action, disrupting peptidoglycan synthesis and cell membrane function. In 2014, the Clinical and Laboratory Standards Institute (CLSI) revised the antimicrobial susceptibility testing method for telavancin, resulting in minimum inhibitory concentration (MIC) determinations that are more accurate and reproducible and demonstrate greater in vitro potency than shown with the previous testing method. The CLSI testing method changes coincided with revised telavancin MIC interpretive break point criteria for susceptibility approved by the US Food and Drug Administration for Staphylococcus aureus (≤0.12 µg/mL), Streptococcus pyogenes (≤0.12 µg/mL), Streptococcus agalactiae (≤0.12 µg/mL), Streptococcus anginosus group (≤0.06 µg/mL), and Enterococcus faecalis (vancomycin susceptible, ≤0.25 µg/mL). Telavancin is equally potent against methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). It demonstrates activity against isolates of heterogeneous vancomycin-intermediate S. aureus and vancomycin-intermediate S. aureus but is poorly active against vancomycin-resistant S. aureus. It also demonstrates potent activity against Staphylococcus epidermidis and Streptococcus spp. (MIC90 ≤0.03 µg/mL). Thus far, it has not been possible to select for high-level telavancin resistance in the laboratory using serially passaged clinical isolates of MRSA and MSSA. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. A comparative study between inhibitory effect of L. lactis and nisin on important pathogenic bacteria in Iranian UF Feta cheese

    Directory of Open Access Journals (Sweden)

    Saeed Mirdamadi

    2015-02-01

    Full Text Available   Introduction : In the present study, the inhibitory effect of nisin-producing Lactococcus lactis during co-culture and pure standard nisin were assessed against selected foodborne pathogenes in growth medium and Iranian UF Feta cheese. In comparison L lactis, not only proves flavor but also plays a better role in microbial quality of Iranian UF Feta cheese as a model of fermented dairy products.   Materials and method s: L. lactis subsp. lactis as nisin producer strain, Listeria monocytogenes, Escherichia coli and Staphylococcus aureus as pathogenic strains were inoculated in Ultra-Filtered Feta cheese. Growth curve of bacterial strains were studied by colony count method in growth medium and UF Feta cheese separately and during co-culture with L. lactis. Nisin production was determined by agar diffusion assay method against susceptible test strain and confirmed by RP-HPLC analysis method.   Results : Counts of L. monocytogenes decreased in cheese sample containing L. lactis and standard nisin, to 103 CFU/g after 7 days and it reached to undetectable level within 2 weeks. S. aureus counts remained at its initial number, 105 CFU/g, after 7 days then decreased to 104 CFU/g on day 14 and it was not detectable on day 28. E. coli numbers increased in both treatments after 7 days and then decreased to 104 CFU/g after 28 days. Despite the increasing number of E. coli in growth medium containing nisin, due to the synergistic effect of nisin and other metabolites produced by Lactococcus lactis and starter cultures, the number of E. coli decreased with slow rate . Discussion and conclusion : The results showed, L. monocytogenes was inhibited by L. lactis before entering the logarithmic phase during co-culture. S. aureus was also inhibited during co-culture, but it showed less sensitivity in comparison with L. monocytogenes. However, the number of E. coli remained steady in co-culture with L. lactis. Also, we found that, in all cheese samples, E

  4. Insecticide resistance status of Myzus persicae in Greece: long-term surveys and new diagnostics for resistance mechanisms.

    Science.gov (United States)

    Voudouris, Costas Ch; Kati, Amalia N; Sadikoglou, Eldem; Williamson, Martin; Skouras, Panagiotis J; Dimotsiou, Ourania; Georgiou, Stella; Fenton, Brian; Skavdis, George; Margaritopoulos, John T

    2016-04-01

    Myzus persicae nicotianae is an important pest in Greece, controlled mainly by neonicotinoids. Monitoring of the aphid populations for resistance mechanisms is essential for effective control. Two new RFLP-based diagnostics for the detection of the M918T (super-kdr pyrethroid resistance) and nAChR R81T (neonicotinoid resistance) mutations were applied, along with other established assays, on 131 nicotianae multilocus genotypes (MLGs) collected from tobacco and peach in Greece in 2012-2013. Furthermore, we present resistance data from aphid clones (>500, mainly nicotianae) collected in 2006-2007. About half of the clones tested with a diagnostic dose of imidacloprid were tolerant. The R81T mutation was not found in the 131 MLGs and 152 clones examined. Over half (58.6%) of a subset of 29 clones showed a 9-36-fold overexpression of CYP6CY3. M918T was found at low to moderate frequencies. The kdr and MACE mechanisms and carboxylesterase-based resistance were found at high frequency in all years. The aphid retains costly resistance mechanisms even in the absence of pressure from certain insecticides, which could be attributed to factors related to climate and genetic properties of the populations. The indication of build-up of resistance/tolerance to neonicotinoids, related to CYP6CY3 overexpression, is a matter of concern. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  5. Influence of food matrix on inactivation of Bacillus cereus by combinations of nisin, pulsed electric field treatment, and carvacrol.

    Science.gov (United States)

    Pol, I E; Mastwujk, H C; Slump, R A; Popa, M E; Smid, E J

    2001-07-01

    Carvacrol was used as a third preservative factor to enhance further the synergy between nisin and pulsed electric field (PEF) treatment against vegetative cells of Bacillus cereus. When applied simultaneously with nisin (0.04 microg/ml), carvacrol (0.5 mM) enhanced the synergy found between nisin and PEF treatment (16.7 kV/cm, 30 pulses) in potassium-N-2-hydroxyethylpiperazine-N-ethanesulfonic acid (HEPES) buffer. The influence of food ingredients on bactericidal activity was tested using skimmed milk that was diluted to 20% with sterile demineralized water. The efficacy of PEF treatment was not affected by the presence of proteins, and results found in HEPES buffer correlated well with results in milk (20%). Nisin showed less activity against B. cereus in milk. Carvacrol was not able to enhance the synergy between nisin and PEF treatment in milk, unless used in high concentrations (1.2 mM). This concentration in itself did not influence the viable count. Carvacrol did act synergistically with PEF treatment in milk, however not in HEPES buffer. This synergy was not influenced by proteins in milk, as 5% milk still allows synergy between carvacrol and PEF treatment to the same extent as 20% milk.

  6. Nisin-activated hydrophobic and hydrophilic surfaces: assessment of peptide adsorption and antibacterial activity against some food pathogens.

    Science.gov (United States)

    Karam, Layal; Jama, Charafeddine; Mamede, Anne-Sophie; Boukla, Samir; Dhulster, Pascal; Chihib, Nour-Eddine

    2013-12-01

    An effective antimicrobial packaging or food contact surface should be able to kill or inhibit micro-organisms that cause food-borne illnesses. Setting up such systems, by nisin adsorption on hydrophilic and hydrophobic surfaces, is still a matter of debate. For this purpose, nisin was adsorbed on two types of low-density polyethylene: the hydrophobic native film and the hydrophilic acrylic acid-treated surface. The antibacterial activity was compared for those two films and it was highly dependent on the nature of the surface and the nisin-adsorbed amount. The hydrophilic surfaces presented higher antibacterial activity and higher amount of nisin than the hydrophobic surfaces. The effectiveness of the activated surfaces was assessed against Listeria innocua and the food pathogens Listeria monocytogenes, Bacillus cereus, and Staphylococcus aureus. S. aureus was more sensitive than the three other test bacteria toward both nisin-functionalized films. Simulation tests to mimic refrigerated temperature showed that the films were effective at 20 and 4 °C with no significant difference between the two temperatures after 30 min of exposure to culture media.

  7. Resistance of green lacewing, Chrysoperla carnea Stephens to nitenpyram: Cross-resistance patterns, mechanism, stability, and realized heritability.

    Science.gov (United States)

    Mansoor, Muhammad Mudassir; Raza, Abu Bakar Muhammad; Abbas, Naeem; Aqueel, Muhammad Anjum; Afzal, Muhammad

    2017-01-01

    The green lacewing, Chrysoperla carnea Stephens (Neuroptera: Chrysopidae) is a major generalist predator employed in integrated pest management (IPM) plans for pest control on many crops. Nitenpyram, a neonicotinoid insecticide has widely been used against the sucking pests of cotton in Pakistan. Therefore, a field green lacewing strain was exposed to nitenpyram for five generations to investigate resistance evolution, cross-resistance pattern, stability, realized heritability, and mechanisms of resistance. Before starting the selection with nitenpyram, a field collected strain showed 22.08-, 23.09-, 484.69- and 602.90-fold resistance to nitenpyram, buprofezin, spinosad and acetamiprid, respectively compared with the Susceptible strain. After continuous selection for five generations (G1-G5) with nitenpyram in the laboratory, the Field strain (Niten-SEL) developed a resistance ratio of 423.95 at G6. The Niten-SEL strain at G6 showed no cross-resistance to buprofezin and acetamiprid and negative cross-resistance to spinosad compared with the Field strain (G1). For resistance stability, the Niten-SEL strain was left unexposed to any insecticide for four generations (G6-G9) and bioassay results at G10 showed that resistance to nitenpyram, buprofezin and spinosad was stable, while resistance to acetamiprid was unstable. The realized heritability values were 0.97, 0.16, 0.03, and -0.16 to nitenpyram, buprofezin, acetamiprid and spinosad, respectively, after five generations of selection. Moreover, the enzyme inhibitors (PBO or DEF) significantly decreased the nitenpyram resistance in the resistant strain, suggesting that resistance was due to microsomal oxidases and esterases. These results are very helpful for integration of green lacewings in IPM programs. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links

    Science.gov (United States)

    Samuel, Varman T.; Shulman, Gerald I.

    2012-01-01

    Insulin resistance is a complex metabolic disorder that defies a single etiological pathway. Accumulation of ectopic lipid metabolites, activation of the unfolded protein response (UPR) pathway and innate immune pathways have all been implicated in the pathogenesis of insulin resistance. However, these pathways are also closely linked to changes in fatty acid uptake, lipogenesis, and energy expenditure that can impact ectopic lipid deposition. Ultimately, accumulation of specific lipid metabolites (diacylglycerols and/or ceramides) in liver and skeletal muscle, may be a common pathway leading to impaired insulin signaling and insulin resistance. PMID:22385956

  9. Alternate efflux pump mechanism may contribute to drug resistance in extensively drug-resistant isolates of Mycobacterium tuberculosis

    Directory of Open Access Journals (Sweden)

    Akbar Kanji

    2016-01-01

    Conclusion: Our data show an nsSNP in the drrA efflux pump gene that may result in upregulation of drug efflux mechanisms in MTB strains. It is therefore imperative to understand the mechanism of efflux and its role in drug resistance, which will enable the identification of new drug targets and development of new drug regimens to counteract the drug efflux mechanism of MTB.

  10. Emergence of macrolide-resistant Campylobacter strains in chicken meat in Poland and the resistance mechanisms involved.

    Science.gov (United States)

    Rożynek, Elżbieta; Maćkiw, Elżbieta; Kamińska, Wanda; Tomczuk, Katarzyna; Antos-Bielska, Małgorzata; Dzierżanowska-Fangrat, Katarzyna; Korsak, Dorota

    2013-07-01

    In this study, we investigated the molecular mechanisms involved in erythromycin resistance in the first resistant Campylobacter strains isolated from chicken meat in Poland, and analyzed their genetic relatedness. A total of 297 samples of raw chicken meat and giblets from retail trade in the Warsaw area collected between 2006 and 2009 were examined. Among 211 Campylobacter strains (52 C. jejuni and 159 C. coli), 10 C. coli isolates (4.7%) were resistant to erythromycin. All the C. jejuni strains were susceptible. Among the high-level macrolide-resistant isolates, two different point mutations within the domain V of the 23S rRNA gene were observed. Eight of the strains had adenine→guanine transitions at position 2075, two other isolates at position 2074. Sequence analysis of ribosomal proteins L4 (rplD) and L22 (rplV) indicated that ribosomal protein modifications did not contribute to macrolide resistance. A mutation in the inverted repeat in the cmeR and cmeABC intergenic region was found in a single resistant strain. The genetic relatedness of Campylobacter isolates showed that two resistant strains obtained from the same production plant in a 2-month interval were genetically identical. The risk of transmission of resistant strains via the food chain highlights the need for constant monitoring of resistance in Campylobacter isolates of human and animal hosts.

  11. Ultrasound-induced new cellular mechanism involved in drug resistance.

    Directory of Open Access Journals (Sweden)

    Mariame A Hassan

    Full Text Available The acoustic effects in a biological milieu offer several scenarios for the reversal of multidrug resistance. In this study, we have observed higher sensitivity of doxorubicin-resistant uterine sarcoma MES-SA/DX5 cells to ultrasound exposure compared to its parent counterpart MES-SA cells; however, the results showed that the acoustic irradiation was genotoxic and could promote neotic division in exposed cells that was more pronounced in the resistant variant. The neotic progeny, imaged microscopically 24 hr post sonication, could contribute in modulating the final cell survival when an apoptotic dose of doxorubicin was combined with ultrasound applied either simultaneously or sequentially in dual-treatment protocols. Depending on the time and order of application of ultrasound and doxorubicin in combination treatments, there was either desensitization of the parent cells or sensitization of the resistant cells to doxorubicin action.

  12. Unravelling the resistance mechanism of lettuce against Nasonovia ribisnigri

    OpenAIRE

    Broeke, ten, C.J.M.

    2013-01-01

    Aphids are serious pests of crop plant species, and host plant resistance is often the most effective and environmentally friendly control strategy to control these pests. One of these aphid pests is the black currant - lettuce aphid, Nasonovia ribisnigri (Mosely), an economically important pest of cultivated lettuce, Lactuca sativa L. Host plant resistance has been used since 1982 to control this aphid species and is mediated by the Nr-gene, originating from wild lettuce Lactuca virosa L. H...

  13. Use of enhanced nisin derivatives in combination with food-grade oils or citric acid to control Cronobacter sakazakii and Escherichia coli O157:H7.

    Science.gov (United States)

    Campion, Alicia; Morrissey, Ruth; Field, Des; Cotter, Paul D; Hill, Colin; Ross, R Paul

    2017-08-01

    Cronobacter sakazakii and Escherichia coli O157:H7 are well known food-borne pathogens that can cause severe disease. The identification of new alternatives to heating to control these pathogens in foods, while reducing the impact on organoleptic properties and nutritional value, is highly desirable. In this study, nisin and its bioengineered variants, nisin V and nisin S29A, are used alone, or in combination with plant essential oils (thymol, carvacrol and trans-cinnamaldehyde) or citric acid, with a view to controlling C. sakazakii and E. coli O157:H7 in laboratory-based assays and model food systems. The use of nisin variants (30 μM) with low concentrations of thymol (0.015%), carvacrol (0.03%) and trans-cinnamaldehyde (0.035%) resulted in extended lag phases of growth compared to those for corresponding nisin A-essential oil combinations. Furthermore, nisin variants (60 μM) used in combination with carvacrol (0.03%) significantly reduced viable counts of E. coli O157:H7 (3-log) and C. sakazakii (4-log) compared to nisin A-carvacrol treatment. Importantly, this increased effectiveness translated into food. More specifically, sub-inhibitory concentrations of nisin variants and carvacrol caused complete inactivation of E. coli O157:H7 in apple juice within 3 h at room temperature compared to that of the equivalent nisin A combination. Furthermore, combinations of commercial Nisaplin and the food additive citric acid reduced C. sakazakii numbers markedly in infant formula within the same 3 h period. These results highlight the potential benefits of combining nisin and variants thereof with carvacrol and/or citric acid for the inhibition of Gram negative food-borne pathogens. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Mechanisms of powdery mildew resistance in the Vitaceae family.

    Science.gov (United States)

    Feechan, Angela; Kabbara, Samuela; Dry, Ian B

    2011-04-01

    The cultivated grapevine, Vitis vinifera, is a member of the Vitaceae family, which comprises over 700 species in 14 genera. Vitis vinifera is highly susceptible to the powdery mildew pathogen Erysiphe necator. However, other species within the Vitaceae family have been reported to show resistance to this fungal pathogen, but little is known about the mechanistic basis of this resistance. Therefore, the frequency of successful E. necator penetration events, in addition to programmed cell death (PCD) responses, were investigated in a representative genotype from a range of different species within the Vitaceae family. The results revealed that penetration resistance and PCD-associated responses, or combinations of both, are employed by the different Vitaceae genera to limit E. necator infection. In order to further characterize the cellular processes involved in the observed penetration resistance, specific inhibitors of the actin cytoskeleton and secretory/endocytic vesicle trafficking function were employed. These inhibitors were demonstrated to successfully break the penetration resistance in V. vinifera against the nonadapted powdery mildew E. cichoracearum. However, the use of these inhibitors with the adapted powdery mildew E. necator unexpectedly revealed that, although secretory and endocytic vesicle trafficking pathways play a crucial role in nonhost penetration resistance, the adapted powdery mildew species may actually require these pathways to successfully penetrate the plant host. © 2010 CSIRO. MOLECULAR PLANT PATHOLOGY © 2010 BSPP AND BLACKWELL PUBLISHING LTD.

  15. Genetic Mechanisms of Antibiotic Resistance and the Role of Antibiotic Adjuvants.

    Science.gov (United States)

    Pontes, Daniela Santos; de Araujo, Rodrigo Santos Aquino; Dantas, Natalina; Scotti, Luciana; Scotti, Marcus Tullius; de Moura, Ricardo Olimpio; Mendonca-Junior, Francisco Jaime Bezerra

    2018-01-01

    The ever increasing number of multidrug-resistant microorganism pathogens has become a great and global public health threat. Antibiotic mechanisms of action and the opposing mechanisms of resistance are intimately associated, but comprehension of the biochemical and molecular functions of such drugs is not a simple exercise. Both the environment, and genetic settings contribute to alterations in phenotypic resistance (natural bacterial evolution), and make it difficult to control the emergence and impacts of antibiotic resistance. Under such circumstances, comprehension of how bacteria develop and/or acquire antibiotic resistance genes (ARG) has a critical role in developing propositions to fight against these superbugs, and to search for new drugs. In this review, we present and discuss both general information and examples of common genetic and molecular mechanisms related to antibiotic resistance, as well as how the expression and interactions of ARGs are important to drug resistance. At the same time, we focus on the recent achievements in the search for antibiotic adjuvants, which help combat antibiotic resistance through deactivation of bacterial mechanisms of action such as β-lactamases. Recent advances involving the use of anti-resistance drugs such as: efflux pump inhibitors; anti-virulence drugs; drugs against quorum sensing; and against type II/III secretion systems are revealed. Such antibiotic adjuvants (as explored herein) collaborate against the problems of antibiotic resistance, and may restore or prolong the therapeutic activity of known antibiotics. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  16. Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Resistant to Fifth-Generation Cephalosporins Reveals Potential Non-mecA Mechanisms of Resistance.

    Science.gov (United States)

    Greninger, Alexander L; Chatterjee, Som S; Chan, Liana C; Hamilton, Stephanie M; Chambers, Henry F; Chiu, Charles Y

    2016-01-01

    Fifth-generation cephalosporins, ceftobiprole and ceftaroline, are promising drugs for treatment of bacterial infections from methicillin-resistant Staphylococcus aureus (MRSA). These antibiotics are able to bind native PBP2a, the penicillin-binding protein encoded by the mecA resistance determinant that mediates broad class resistance to nearly all other beta-lactam antibiotics, at clinically achievable concentrations. Mechanisms of resistance to ceftaroline based on mecA mutations have been previously described. Here we compare the genomes of 11 total parent-daughter strains of Staphylococcus aureus for which specific selection by serial passaging with ceftaroline or ceftobiprole was used to identify novel non-mecA mechanisms of resistance. All 5 ceftaroline-resistant strains, derived from 5 different parental strains, contained mutations directly upstream of the pbp4 gene (coding for the PBP4 protein), including four with the same thymidine insertion located 377 nucleotides upstream of the promoter site. In 4 of 5 independent ceftaroline-driven selections, we also isolated mutations to the same residue (Asn138) in PBP4. In addition, mutations in additional candidate genes such as ClpX endopeptidase, PP2C protein phosphatase and transcription terminator Rho, previously undescribed in the context of resistance to ceftaroline or ceftobiprole, were detected in multiple selections. These genomic findings suggest that non-mecA mechanisms, while yet to be encountered in the clinical setting, may also be important in mediating resistance to 5th-generation cephalosporins.

  17. Whole-Genome Sequencing of Methicillin-Resistant Staphylococcus aureus Resistant to Fifth-Generation Cephalosporins Reveals Potential Non-mecA Mechanisms of Resistance.

    Directory of Open Access Journals (Sweden)

    Alexander L Greninger

    Full Text Available Fifth-generation cephalosporins, ceftobiprole and ceftaroline, are promising drugs for treatment of bacterial infections from methicillin-resistant Staphylococcus aureus (MRSA. These antibiotics are able to bind native PBP2a, the penicillin-binding protein encoded by the mecA resistance determinant that mediates broad class resistance to nearly all other beta-lactam antibiotics, at clinically achievable concentrations. Mechanisms of resistance to ceftaroline based on mecA mutations have been previously described. Here we compare the genomes of 11 total parent-daughter strains of Staphylococcus aureus for which specific selection by serial passaging with ceftaroline or ceftobiprole was used to identify novel non-mecA mechanisms of resistance. All 5 ceftaroline-resistant strains, derived from 5 different parental strains, contained mutations directly upstream of the pbp4 gene (coding for the PBP4 protein, including four with the same thymidine insertion located 377 nucleotides upstream of the promoter site. In 4 of 5 independent ceftaroline-driven selections, we also isolated mutations to the same residue (Asn138 in PBP4. In addition, mutations in additional candidate genes such as ClpX endopeptidase, PP2C protein phosphatase and transcription terminator Rho, previously undescribed in the context of resistance to ceftaroline or ceftobiprole, were detected in multiple selections. These genomic findings suggest that non-mecA mechanisms, while yet to be encountered in the clinical setting, may also be important in mediating resistance to 5th-generation cephalosporins.

  18. Origin and evolution of antibiotic resistance: the common mechanisms of emergence and spread in water bodies.

    Science.gov (United States)

    Lupo, Agnese; Coyne, Sébastien; Berendonk, Thomas Ulrich

    2012-01-01

    The environment, and especially freshwater, constitutes a reactor where the evolution and the rise of new resistances occur. In water bodies such as waste water effluents, lakes, and rivers or streams, bacteria from different sources, e.g., urban, industrial, and agricultural waste, probably selected by intensive antibiotic usage, are collected and mixed with environmental species. This may cause two effects on the development of antibiotic resistances: first, the contamination of water by antibiotics or other pollutants lead to the rise of resistances due to selection processes, for instance, of strains over-expressing broad range defensive mechanisms, such as efflux pumps. Second, since environmental species are provided with intrinsic antibiotic resistance mechanisms, the mixture with allochthonous species is likely to cause genetic exchange. In this context, the role of phages and integrons for the spread of resistance mechanisms appears significant. Allochthonous species could acquire new resistances from environmental donors and introduce the newly acquired resistance mechanisms into the clinics. This is illustrated by clinically relevant resistance mechanisms, such as the fluoroquinolones resistance genes qnr. Freshwater appears to play an important role in the emergence and in the spread of antibiotic resistances, highlighting the necessity for strategies of water quality improvement. We assume that further knowledge is needed to better understand the role of the environment as reservoir of antibiotic resistances and to elucidate the link between environmental pollution by anthropogenic pressures and emergence of antibiotic resistances. Only an integrated vision of these two aspects can provide elements to assess the risk of spread of antibiotic resistances via water bodies and suggest, in this context, solutions for this urgent health issue.

  19. Multiple mechanisms increase levels of resistance in Rapistrum rugosum to ALS herbicides

    Directory of Open Access Journals (Sweden)

    Zhara M Hatami

    2016-02-01

    Full Text Available Rapistrum rugosum (turnip weed is a common weed of wheat fields in Iran, which is most often controlled by tribenuron-methyl (TM, a sulfonylurea (SU belonging to the acetolactate synthase (ALS inhibiting herbicides group. Several cases of unexplained control failure of R. rugosum by TM have been seen, especially in Golestan province-Iran. Hence, there is lack of research in evaluation of the level of resistance of the R. rugosum populations to TM, using whole plant dose–response and enzyme assays, then investigating some potential resistance mechanisms Results revealed that the resistance factor (RF for resistant (R populations was 2.5 to 6.6 fold higher than susceptible (S plant. Neither foliar retention, nor 14C-TM absorption and translocation were the mechanisms responsible for resistance in turnip weed. Metabolism of TM was the second resistant mechanism in two populations (Ag-R5 and G-1, in which three metabolites were found. The concentration of TM for 50% inhibition of ALS enzyme activity in vitro showed a high level of resistance to the herbicide (resistance factors were from 28 to 38 and cross-resistance to sulfonyl-aminocarbonyl-triazolinone (SCT, pyrimidinyl-thiobenzoate (PTB and triazolopyrimidine (TP, with no cross-resistance to imidazolinone (IMI. Substitution Pro 197 to Ser 197 provided resistance to four of five ALS-inhibiting herbicides including SU, TP, PTB and SCT with no resistance to IMI. These results documented the first case of R. rugosum resistant population worldwide and demonstrated that both RST and NRST mechanisms are involved to the resistance level to TM.

  20. Insecticide Resistance Mechanisms in the Green Peach Aphid Myzus persicae (Hemiptera: Aphididae) I: A Transcriptomic Survey

    Science.gov (United States)

    Silva, Andrea X.; Jander, Georg; Samaniego, Horacio; Ramsey, John S; Figueroa, Christian C.

    2012-01-01

    Background Insecticide resistance is one of the best examples of rapid micro-evolution found in nature. Since the development of the first synthetic insecticide in 1939, humans have invested considerable effort to stay ahead of resistance phenotypes that repeatedly develop in insects. Aphids are a group of insects that have become global pests in agriculture and frequently exhibit insecticide resistance. The green peach aphid, Myzus persicae, has developed resistance to at least seventy different synthetic compounds, and different insecticide resistance mechanisms have been reported worldwide. Methodology/Principal Findings To further characterize this resistance, we analyzed genome-wide transcriptional responses in three genotypes of M. persicae, each exhibiting different resistance mechanisms, in response to an anti-cholinesterase insecticide. The sensitive genotype (exhibiting no resistance mechanism) responded to the insecticide by up-regulating 183 genes primarily ones related to energy metabolism, detoxifying enzymes, proteins of extracellular transport, peptidases and cuticular proteins. The second genotype (resistant through a kdr sodium channel mutation), up-regulated 17 genes coding for detoxifying enzymes, peptidase and cuticular proteins. Finally, a multiply resistant genotype (carrying kdr and a modified acetylcholinesterase), up-regulated only 7 genes, appears not to require induced insecticide detoxification, and instead down-regulated many genes. Conclusions/Significance This study suggests strongly that insecticide resistance in M. persicae is more complex that has been described, with the participation of a broad array of resistance mechanisms. The sensitive genotype exhibited the highest transcriptional plasticity, accounting for the wide range of potential adaptations to insecticides that this species can evolve. In contrast, the multiply resistant genotype exhibited a low transcriptional plasticity, even for the expression of genes encoding

  1. Evolution of antibiotic resistance is linked to any genetic mechanism affecting bacterial duration of carriage.

    Science.gov (United States)

    Lehtinen, Sonja; Blanquart, François; Croucher, Nicholas J; Turner, Paul; Lipsitch, Marc; Fraser, Christophe

    2017-01-31

    Understanding how changes in antibiotic consumption affect the prevalence of antibiotic resistance in bacterial pathogens is important for public health. In a number of bacterial species, including Streptococcus pneumoniae, the prevalence of resistance has remained relatively stable despite prolonged selection pressure from antibiotics. The evolutionary processes allowing the robust coexistence of antibiotic sensitive and resistant strains are not fully understood. While allelic diversity can be maintained at a locus by direct balancing selection, there is no evidence for such selection acting in the case of resistance. In this work, we propose a mechanism for maintaining coexistence at the resistance locus: linkage to a second locus that is under balancing selection and that modulates the fitness effect of resistance. We show that duration of carriage plays such a role, with long duration of carriage increasing the fitness advantage gained from resistance. We therefore predict that resistance will be more common in strains with a long duration of carriage and that mechanisms maintaining diversity in duration of carriage will also maintain diversity in antibiotic resistance. We test these predictions in S. pneumoniae and find that the duration of carriage of a serotype is indeed positively correlated with the prevalence of resistance in that serotype. These findings suggest heterogeneity in duration of carriage is a partial explanation for the coexistence of sensitive and resistant strains and that factors determining bacterial duration of carriage will also affect the prevalence of resistance.

  2. Charge dividing mechanism on resistive electrode in position-sensitive detectors

    International Nuclear Information System (INIS)

    Radeka, V.; Rehak, P.

    1978-10-01

    A complete charge-division mechanism, including both the diffusion and the electromagnetic wave propagation on resistive electrodes, is presented. The charge injected into such a transmission line divides between the two ends according to the ratio of resistancies and independently of the value of the line resistance, of the propagation mechanism and of the distribution of inductance and capacitance along the line. The shortest charge division time is achieved for Rl = 2π (L/C) 1 / 2 , where R, L, C are resistance, inductance and capacitance per unit length and l is the length of the line

  3. A new detection method for a newly revealed mechanism of pyrethroid resistance development in Varroa destructor.

    Science.gov (United States)

    Strachecka, Aneta; Borsuk, Grzegorz; Olszewski, Krzysztof; Paleolog, Jerzy

    2015-11-01

    The Varroa destructor mite has recently displayed an ever increasing resistance to new drugs, contributing to CCD proliferation. This work was aimed at determining new viable methods for identifying the pyrethroid resistance of V. destructor and DNA methylation in resistant and sensitive mites. DNA was extracted from Varroa mites. Nucleotide changes in the DNA of pyrethroid-resistant, pyrethroid-sensitive, and control mites were identified with polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) in the case of five mitochondrial gene fragments. More bands were observed in the drug-resistant mites than in the other two groups. Sequencing confirmed these observations. Decreased global DNA methylation levels were observed in the pyrethroid-resistant mites. There exists a previously undescribed mechanism of pyrethroid resistance development in Varroa mites. The PCR-SSCP methods can be considered and further developed as useful tools for detecting V. destructor resistance.

  4. Macrolide resistance mechanisms and virulence factors in erythromycin-resistant Campylobacter species isolated from chicken and swine feces and carcasses.

    Science.gov (United States)

    Lim, Suk-Kyung; Moon, Dong-Chan; Chae, Myung Hwa; Kim, Hae Ji; Nam, Hyang-Mi; Kim, Su-Ran; Jang, Gum-Chan; Lee, Kichan; Jung, Suk-Chan; Lee, Hee-Soo

    2017-01-10

    Resistance to antimicrobials was measured in 73 isolates of Campylobacter jejuni (C. jejuni) and 121 isolates of Campylobacter coli (C. coli) from chicken and swine feces and carcasses in Korea. Both bacterial species showed the highest resistance to (fluoro) quinolones (ciprofloxacin and nalidixic acid) out of the nine antimicrobials tested. Erythromycin resistance was much higher in C. coli (19.0%, 23/121) than in C. jejuni (6.8%, 5/73). The mutation in the 23S rRNA gene was primarily responsible for macrolide resistance in Campylobacter isolates. Several amino acid substitutions in the L4 and L22 ribosomal proteins may play a role in the mechanism of resistance, but the role requires further evaluation. A total of eight virulence genes were detected in 28 erythromycin-resistant Campylobacter isolates. All C. jejuni isolates carried more than four such genes, while C. coli isolates carried fewer than three such genes. The high rate of resistance highlights the need to employ more prudent use of critically important antimicrobials, such as fluoroquinolones and macrolides, in swine and poultry production, and to more carefully monitor antimicrobial resistance in Campylobacter isolates in food animals.

  5. Creatine loading, resistance exercise performance, and muscle mechanics.

    Science.gov (United States)

    Stevenson, S W; Dudley, G A

    2001-11-01

    We tested the null hypothesis that creatine monohydrate loading (20 g per day for 7 days, n = 18) would not alter resistance exercise performance, isometric strength, or in vivo contractile properties of the quadriceps femoris muscle compared with loading with placebo (n = 13) in resistance-trained subjects. For the entire study group, the 1 repetition maximum (1RM) and 5-set performance (the number of repetitions) for unilateral, dynamic knee extension increased slightly (2% and 5%, respectively) after dietary supplementation, and these responses did not differ by condition. Maximal voluntary isometric torque and the rate of torque development did not change. During electromyostimulation, torque development and relaxation time were also unaffected. Our data suggest that creatine loading does not augment unilateral strength or multiset resistance exercise performance for knee extensions compared with placebo loading.

  6. The study of resistant mechanisms and reversal in an imatinib resistant Ph+ acute lymphoblastic leukemia cell line.

    Science.gov (United States)

    Xing, Hongyun; Yang, Xi; Liu, Ting; Lin, Juan; Chen, Xiaoyi; Gong, Yuping

    2012-04-01

    In this study, we established an imatinib resistant Ph+ acute lymphoblastic leukemia (ALL) cell line SUP-B15/RI in vitro and studied the mechanism of imatinib resistance. Our results showed that the BCR-ABL1 fusion gene and the mdr1 gene were 6.1 times and 1.7 times, respectively, as high as that of parental SUP-B15 cell line. We found no mutation in the Abl kinase domain of SUP-B15/RI. Furthermore, the detection of cell signaling pathway of PI3K/AKT/mTOR, RAS/RAF, NF-κB, JNK and STAT showed the up-regulation of phosphorylation of AKT, mTOR, P70S6K, and RAF, ERK, and MEK, down-regulation of PTEN and 4EBP-1, and no change in other cell signaling pathways in SUP-B15/RI. However, dasatinib and nilotinib showed partial resistance. Interestingly, bortezomib had no resistance. Imatinib combination with rapamycin had synergistic effect on overcoming the resistance. Altogether, over-expression of BCR-ABL1 and mdr1 gene were involved in the resistance mechanisms, and up-regulation of the cell signaling pathways of PI3K/AKT/mTOR, RAS/RAF in SUP-B15/RI cell line may be correlated with them. The SUP-B15/RI cell line was also resistant to the second generation tyrosine kinase, dasatinib, and nilotinib, not bortezomib. The combination of imatinib with rapamycin can partially overcome the resistance and blockade of the ubiquitin-proteasome can be also a promising pathway to overcome imatinib resistance. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Mechanisms of Therapy Resistance in Patient-Derived Xenograft Models of BRCA1-Deficient Breast Cancer.

    Science.gov (United States)

    Ter Brugge, Petra; Kristel, Petra; van der Burg, Eline; Boon, Ute; de Maaker, Michiel; Lips, Esther; Mulder, Lennart; de Ruiter, Julian; Moutinho, Catia; Gevensleben, Heidrun; Marangoni, Elisabetta; Majewski, Ian; Józwiak, Katarzyna; Kloosterman, Wigard; van Roosmalen, Markus; Duran, Karen; Hogervorst, Frans; Turner, Nick; Esteller, Manel; Cuppen, Edwin; Wesseling, Jelle; Jonkers, Jos

    2016-11-01

    Although BRCA1-deficient tumors are extremely sensitive to DNA-damaging drugs and poly(ADP-ribose) polymerase (PARP) inhibitors, recurrences do occur and, consequently, resistance to therapy remains a serious clinical problem. To study the underlying mechanisms, we induced therapy resistance in patient-derived xenograft (PDX) models of BRCA1-mutated and BRCA1-methylated triple-negative breast cancer. A cohort of 75 mice carrying BRCA1-deficient breast PDX tumors was treated with cisplatin, melphalan, nimustine, or olaparib, and treatment sensitivity was determined. In tumors that acquired therapy resistance, BRCA1 expression was investigated using quantitative real-time polymerase chain reaction and immunoblotting. Next-generation sequencing, methylation-specific multiplex ligation-dependent probe amplification (MLPA) and Target Locus Amplification (TLA)-based sequencing were used to determine mechanisms of BRCA1 re-expression in therapy-resistant tumors. BRCA1 protein was not detected in therapy-sensitive tumors but was found in 31 out of 42 resistant cases. Apart from previously described mechanisms involving BRCA1-intragenic deletions and loss of BRCA1 promoter hypermethylation, a novel resistance mechanism was identified in four out of seven BRCA1-methylated PDX tumors that re-expressed BRCA1 but retained BRCA1 promoter hypermethylation. In these tumors, we found de novo gene fusions that placed BRCA1 under the transcriptional control of a heterologous promoter, resulting in re-expression of BRCA1 and acquisition of therapy resistance. In addition to previously described clinically relevant resistance mechanisms in BRCA1-deficient tumors, we describe a novel resistance mechanism in BRCA1-methylated PDX tumors involving de novo rearrangements at the BRCA1 locus, demonstrating that BRCA1-methylated breast cancers may acquire therapy resistance via both epigenetic and genetic mechanisms. © The Author 2016. Published by Oxford University Press. All rights reserved

  8. Mechanisms of quinolone resistance in Salmonella spp. / Mecanismos de resistência às quinolonas em Salmonella spp.

    Directory of Open Access Journals (Sweden)

    Tereza Cristina Rocha Moreira de Oliveira

    2010-07-01

    Full Text Available Salmonellosis is a common and widespread zoonotic disease of humans and a frequent cause of foodborne disease. Treatment of severe and systemic salmonellosis is usually done with fluoroquinolones. In this review resistance mechanisms of Salmonella to quinolones are discussed. Single point mutations in the quinolone resistant determining region (QRDR of the gyrA gene may be sufficient to generate high levels of resistance to non-fluorated quinolones and also may decrease the fluoroquinolones susceptibility. Other resistance mechanisms that should be considered are mutations in parC gene, the possibility of acquiring resistance through plasmidial transference and hyper-expression of efflux pumps. Fluoroquinolones resistance is still relatively uncommon in Salmonella compared to other species belonging to the Enterobacteriaceae family. However, the more careful use of fluoroquinolones in veterinary and human medicine is essential to decrease the selective pressure which can avoid the emergence and spread of resistant clones and consequently maintain the clinical efficacy of this group of antibiotics.A salmonelose é uma zoonose de importância mundial e uma das mais freqüentes doenças de origem alimentar. As fluoroquinolonas são a principal opção para o tratamento de salmoneloses graves ou sistêmicas. Esta revisão de literatura teve como objetivo apresentar os principais mecanismos envolvidos na resistência de Salmonella spp a estes antimicrobianos. Mutações de ponto na Região Determinante de Resistência à Quinolona (QRDR do gene gyrA podem gerar altos níveis de resistência a quinolonas não-fluoradas, além de reduzir a suscetibilidade as fluoroquinolonas. Outros mecanismos de resistência que também precisam ser considerados são as mutações no gene parC, a possibilidade do envolvimento de plasmídios de resistência e o sistema de efluxo ativo. A resistência às fluoroquinolonas ainda é incomum em Salmonella spp., quando

  9. A study on the mechanism of resistance to streptomycin in ...

    African Journals Online (AJOL)

    use

    2011-12-12

    1973), and the length of lesions on the inoculated leaf was measured after 15 days. DNA isolation. DNA was isolated from the wild-type isolate and resistant strains as described by Ausubel et al. (1987). After the bacteria were ...

  10. Evaluation the mechanisms of erythromycin and penicillin resistance ...

    African Journals Online (AJOL)

    user

    2012-01-12

    Jan 12, 2012 ... primer (Table 1) and 10 µl of DNA templates (Fukushima et al.,. 2008). PCR amplification was carried with the cycling parameters as follows: after an initial denaturation .... isolated from children in Japan. Mutations in pbp2x were observed in several strains presenting intermediate resistance to penicillin.

  11. Molecular Mechanisms of Antibiotic Resistance in Helicobacter pylori

    NARCIS (Netherlands)

    M.M. Gerrits (Monique)

    2004-01-01

    textabstractAn estimated 4 to 5 million individuals in the Netherlands are actively infected with Helicobacter pylori. Eradication of this bacterium becomes more difficult as the prevalence of antibiotic resistance is increasing worldwide. Most H. pylori infections are now diagnosed by

  12. Molecular mechanisms of insulin resistance | Pillay | South African ...

    African Journals Online (AJOL)

    This review discusses recent advances in understanding of the structure and function of the insulin receptor and insulin action, and how these relate to the clinical aspects of insulin resistance associated with non-insulin-dependent diabetes and other disorders. Improved understanding of the molecular basis of insulin ...

  13. Unravelling the resistance mechanism of lettuce against Nasonovia ribisnigri

    NARCIS (Netherlands)

    Broeke, ten C.J.M.

    2013-01-01

    Aphids are serious pests of crop plant species, and host plant resistance is often the most effective and environmentally friendly control strategy to control these pests. One of these aphid pests is the black currant - lettuce aphid, Nasonovia ribisnigri (Mosely), an economically

  14. A study on the mechanism of resistance to streptomycin in ...

    African Journals Online (AJOL)

    11 streptomycin-resistant mutants of Xanthomonas oryzae pv. oryzae were obtained by streptomycin selection. These mutants could grow at 100 μg ml-1 of streptomycin while the wild-type strain (PXO99) could not grow at 2 μg ml-1. Specific primers based on the conserved region of X. oryzae pv. oryzae were designed and ...

  15. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Winyoo Chowanadisai

    Full Text Available The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05 (S2 Table. Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.

  16. Acaricide resistance and resistance mechanisms in Tetranychus urticae populations from rose greenhouses in the Netherlands

    NARCIS (Netherlands)

    Khajehali, J.; Van Nieuwenhuyse, P.; Demaeght, P.; Tirry, L.; Van Leeuwen, T.

    2011-01-01

    BACKGROUND: Spider mites are important crop pests that rapidly develop resistance to acaricides. To investigate whether acaricide resistance is a threat to greenhouse rose culture in the Netherlands, the susceptibility of 15 strains of Tetranychus urticae was tested to several currently used

  17. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs.

    Science.gov (United States)

    Soares, Geisla Mary Silva; Figueiredo, Luciene Cristina; Faveri, Marcelo; Cortelli, Sheila Cavalca; Duarte, Poliana Mendes; Feres, Magda

    2012-01-01

    Antibiotics are important adjuncts in the treatment of infectious diseases, including periodontitis. The most severe criticisms to the indiscriminate use of these drugs are their side effects and, especially, the development of bacterial resistance. The knowledge of the biological mechanisms involved with the antibiotic usage would help the medical and dental communities to overcome these two problems. Therefore, the aim of this manuscript was to review the mechanisms of action of the antibiotics most commonly used in the periodontal treatment (i.e. penicillin, tetracycline, macrolide and metronidazole) and the main mechanisms of bacterial resistance to these drugs. Antimicrobial resistance can be classified into three groups: intrinsic, mutational and acquired. Penicillin, tetracycline and erythromycin are broad-spectrum drugs, effective against gram-positive and gram-negative microorganisms. Bacterial resistance to penicillin may occur due to diminished permeability of the bacterial cell to the antibiotic; alteration of the penicillin-binding proteins, or production of β-lactamases. However, a very small proportion of the subgingival microbiota is resistant to penicillins. Bacteria become resistant to tetracyclines or macrolides by limiting their access to the cell, by altering the ribosome in order to prevent effective binding of the drug, or by producing tetracycline/macrolide-inactivating enzymes. Periodontal pathogens may become resistant to these drugs. Finally, metronidazole can be considered a prodrug in the sense that it requires metabolic activation by strict anaerobe microorganisms. Acquired resistance to this drug has rarely been reported. Due to these low rates of resistance and to its high activity against the gram-negative anaerobic bacterial species, metronidazole is a promising drug for treating periodontal infections.

  18. Mechanisms of action of systemic antibiotics used in periodontal treatment and mechanisms of bacterial resistance to these drugs

    Directory of Open Access Journals (Sweden)

    Geisla Mary Silva Soares

    2012-06-01

    Full Text Available Antibiotics are important adjuncts in the treatment of infectious diseases, including periodontitis. The most severe criticisms to the indiscriminate use of these drugs are their side effects and, especially, the development of bacterial resistance. The knowledge of the biological mechanisms involved with the antibiotic usage would help the medical and dental communities to overcome these two problems. Therefore, the aim of this manuscript was to review the mechanisms of action of the antibiotics most commonly used in the periodontal treatment (i.e. penicillin, tetracycline, macrolide and metronidazole and the main mechanisms of bacterial resistance to these drugs. Antimicrobial resistance can be classified into three groups: intrinsic, mutational and acquired. Penicillin, tetracycline and erythromycin are broad-spectrum drugs, effective against gram-positive and gram-negative microorganisms. Bacterial resistance to penicillin may occur due to diminished permeability of the bacterial cell to the antibiotic; alteration of the penicillin-binding proteins, or production of β-lactamases. However, a very small proportion of the subgingival microbiota is resistant to penicillins. Bacteria become resistant to tetracyclines or macrolides by limiting their access to the cell, by altering the ribosome in order to prevent effective binding of the drug, or by producing tetracycline/macrolide-inactivating enzymes. Periodontal pathogens may become resistant to these drugs. Finally, metronidazole can be considered a prodrug in the sense that it requires metabolic activation by strict anaerobe microorganisms. Acquired resistance to this drug has rarely been reported. Due to these low rates of resistance and to its high activity against the gram-negative anaerobic bacterial species, metronidazole is a promising drug for treating periodontal infections.

  19. Mechanisms underlying skeletal muscle insulin resistance induced by fatty acids: importance of the mitochondrial function

    Directory of Open Access Journals (Sweden)

    Martins Amanda R

    2012-02-01

    Full Text Available Abstract Insulin resistance condition is associated to the development of several syndromes, such as obesity, type 2 diabetes mellitus and metabolic syndrome. Although the factors linking insulin resistance to these syndromes are not precisely defined yet, evidence suggests that the elevated plasma free fatty acid (FFA level plays an important role in the development of skeletal muscle insulin resistance. Accordantly, in vivo and in vitro exposure of skeletal muscle and myocytes to physiological concentrations of saturated fatty acids is associated with insulin resistance condition. Several mechanisms have been postulated to account for fatty acids-induced muscle insulin resistance, including Randle cycle, oxidative stress, inflammation and mitochondrial dysfunction. Here we reviewed experimental evidence supporting the involvement of each of these propositions in the development of skeletal muscle insulin resistance induced by saturated fatty acids and propose an integrative model placing mitochondrial dysfunction as an important and common factor to the other mechanisms.

  20. Novel drug-resistance mechanisms of pemetrexed-treated non-small cell lung cancer.

    Science.gov (United States)

    Tanino, Ryosuke; Tsubata, Yukari; Harashima, Nanae; Harada, Mamoru; Isobe, Takeshi

    2018-03-30

    Pemetrexed (PEM) improves the overall survival of patients with advanced non-small cell lung cancer (NSCLC) when administered as maintenance therapy. However, PEM resistance often appears during the therapy. Although thymidylate synthase is known to be responsible for PEM resistance, no other mechanisms have been investigated in detail. In this study, we explored new drug resistance mechanisms of PEM-treated NSCLC using two combinations of parental and PEM-resistant NSCLC cell lines from PC-9 and A549. PEM increased the apoptosis cells in parental PC-9 and the senescent cells in parental A549. However, such changes were not observed in the respective PEM-resistant cell lines. Quantitative RT-PCR analysis revealed that, besides an increased gene expression of thymidylate synthase in PEM-resistant PC-9 cells, the solute carrier family 19 member1 ( SLC19A1) gene expression was markedly decreased in PEM-resistant A549 cells. The siRNA-mediated knockdown of SLC19A1 endowed the parental cell lines with PEM resistance. Conversely, PEM-resistant PC-9 cells carrying an epidermal growth factor receptor (EGFR) mutation acquired resistance to a tyrosine kinase inhibitor erlotinib. Although erlotinib can inhibit the phosphorylation of EGFR and Erk, it is unable to suppress the phosphorylation of Akt in PEM-resistant PC-9 cells. Additionally, PEM-resistant PC-9 cells were less sensitive to the PI3K inhibitor LY294002 than parental PC-9 cells. These results indicate that SLC19A1 negatively regulates PEM resistance in NSCLC, and that EGFR-tyrosine-kinase-inhibitor resistance was acquired with PEM resistance through Akt activation in NSCLC harboring EGFR mutations.

  1. Multiple mechanisms underlying acquired resistance to taxanes in selected docetaxel-resistant MCF-7 breast cancer cells

    OpenAIRE

    Wang, Harris; Vo, The; Hajar, Ali; Li, Sarah; Chen, Xinmei; Parissenti, Amadeo M; Brindley, David N; Wang, Zhixiang

    2014-01-01

    Background Chemoresistance is a major factor involved in a poor response and reduced overall survival in patients with advanced breast cancer. Although extensive studies have been carried out to understand the mechanisms of chemoresistance, many questions remain unanswered. Methods In this research, we used two isogenic MCF-7 breast cancer cell lines selected for resistance to doxorubicin (MCF-7DOX) or docetaxel (MCF-7TXT) and the wild type parental cell line (MCF-7CC) to study mechanisms und...

  2. Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase.

    OpenAIRE

    Piton , Jérémie; Petrella , Stéphanie; Delarue , Marc; André-Leroux , Gwénaëlle; Jarlier , Vincent; Aubry , Alexandra; Mayer , Claudine

    2010-01-01

    International audience; Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural...

  3. Acaricide resistance mechanisms in Rhipicephalus (Boophilus microplus Mecanismos de resistência aos acaricidas em Rhipicephalus (Boophilus microplus

    Directory of Open Access Journals (Sweden)

    Felix David Guerrero

    2012-03-01

    Full Text Available Acaricide resistance has become widespread in countries where cattle ticks, Rhipicephalus (Boophilus microplus, are a problem. Resistance arises through genetic changes in a cattle tick population that causes modifications to the target site, increased metabolism or sequestration of the acaricide, or reduced ability of the acaricide to penetrate through the outer protective layers of the tick’s body. We review the molecular and biochemical mechanisms of acaricide resistance that have been shown to be functional in R. (B. microplus. From a mechanistic point of view, resistance to pyrethroids has been characterized to a greater degree than any other acaricide class. Although a great deal of research has gone into discovery of the mechanisms that cause organophosphate resistance, very little is defined at the molecular level and organophosphate resistance seems to be maintained through a complex and multifactorial process. The resistance mechanisms for other acaricides are less well understood. The target sites of fipronil and the macrocyclic lactones are known and resistance mechanism studies are in the early stages. The target site of amitraz has not been definitively identified and this is hampering mechanistic studies on this acaricide.A resistência aos acaricidas tornou-se amplamente difundida nos países onde os carrapatos bovinos, Rhipicephalus .Boophilus. microplus, são um problema. A resistência surge por meio de alterações genéticas em umapopulação de carrapatos que causam modificações no local de ação, aumento do metabolismo ou sequestro do acaricida, ou ainda redução na capacidade do acaricida em penetrar através das camadas protetoras do corpo do carrapato. Neste artigo, foram revisados os mecanismos moleculares e bioquímicos da resistência aos acaricidas que ocorrem em R. (B. microplus. A partir de um ponto de vista dos mecanismos envolvidos, a resistência aos piretróides tem sido caracterizada em maior grau do

  4. Evolution of amoxicillin resistance of Helicobacter pylori in vitro: characterization of resistance mechanisms.

    Science.gov (United States)

    Qureshi, Nadia N; Gallaher, Brandon; Schiller, Neal L

    2014-12-01

    Helicobacter pylori is the major cause of peptic ulcers and gastric cancer in humans. Treatment involves a two or three drug cocktail, typically including amoxicillin. Increasing levels of resistance to amoxicillin contribute to treatment failures, and higher levels of resistance are believed to be due to multiple genetic mutations. In this study, we examined the progression of spontaneous genetic mutations that contribute to amoxicillin resistance in H. pylori when exposed to increasing concentrations of amoxicillin in vitro. During the selection process, we isolated five strains each of which had progressively higher levels of resistance. Using a whole genome sequencing approach, we identified mutations in a number of genes, notably pbp1, pbp2, hefC, hopC, and hofH, and by sequencing these genes in each isolate we were able to map the order and gradual accumulation of mutations in these isolates. These five isolates, each expressing multiple mutated genes and four transformed strains expressing individually mutated pbp1, hefC, or hofH, were characterized using minimum inhibitory concentrations, amoxicillin uptake, and efflux studies. Our results indicate that mutations in pbp1, hefC, hopC, hofH, and possibly pbp2 contribute to H. pylori high-level amoxicillin resistance. The data also provide evidence for the complexity of the evolution of amoxicillin resistance in H. pylori and indicate that certain families of genes might be more susceptible to amoxicillin resistance mutations than others.

  5. Mechanisms of Trastuzumab resistance in ErbB2-driven breast cancer and newer opportunities to overcome therapy resistance

    Directory of Open Access Journals (Sweden)

    Tameka A Bailey

    2011-01-01

    Full Text Available The Human Epidermal Growth Factor Receptor 2 (Her2, ErbB2 or Neu is overexpressed in about 20 - 25% of breast cancers and is causally linked to oncogenesis, providing opportunities for targeted therapy. Trastuzumab (Herceptin™, Genentech Inc, San Francisco, CA, a humanized monoclonal antibody against ErbB2, is a successful example of this concept and has vastly improved the response to treatment and overall survival in a majority of ErbB2+ breast cancer patients. However, lack of response in some patients as well as relapse during the course of therapy in others, continue to challenge researchers and clinicians alike towards a better understanding of the fundamental mechanisms of Trastuzumab action and resistance to treatment. The exact in vivo mechanism of action of Trastuzumab remains enigmatic, given its direct effects on the ErbB2 signaling pathway as well as indirect contributions from the immune system, by virtue of the ability of Trastuzumab to elicit Antibody-Dependent Cellular Cytotoxicity. Consequently, multiple mechanisms of resistance have been proposed. We present here a comprehensive review of our current understanding of the mechanisms, both of Trastuzumab action and clinical resistance to Trastuzumab-based therapies. We also review newer strategies (based on ErbB2 receptor biology that are being explored to overcome resistance to Trastuzumab therapy.

  6. Analysis of antimicrobial resistance mechanisms in multi-drug resistant (MDR) Salmonella enterica by high-throughput DNA sequencing

    Science.gov (United States)

    Background: Multi drug resistant (MDR) Salmonella enterica is found in food animals and may consequently pose a risk to humans through food borne transmission. To understand the mechanisms that drive this problem, the genetic elements associated with MDR need to be determined. These MDR elements in ...

  7. Repeatable change in electrical resistance of Si surface by mechanical and electrical nanoprocessing.

    Science.gov (United States)

    Miyake, Shojiro; Suzuki, Shota

    2014-01-01

    The properties of mechanically and electrically processed silicon surfaces were evaluated by atomic force microscopy (AFM). Silicon specimens were processed using an electrically conductive diamond tip with and without vibration. After the electrical processing, protuberances were generated and the electric current through the silicon surface decreased because of local anodic oxidation. Grooves were formed by mechanical processing without vibration, and the electric current increased. In contrast, mechanical processing with vibration caused the surface to protuberate and the electrical resistance increased similar to that observed for electrical processing. With sequential processing, the local oxide layer formed by electrical processing can be removed by mechanical processing using the same tip without vibration. Although the electrical resistance is decreased by the mechanical processing without vibration, additional electrical processing on the mechanically processed area further increases the electrical resistance of the surface.

  8. Effects of Mentha longifolia L. essential oil and nisin alone and in combination on Bacillus cereus and Bacillus subtilis in a food model and bacterial ultrastructural changes.

    Science.gov (United States)

    Pajohi, Mohamad Reza; Tajik, Hossein; Farshid, Amir Abbas; Basti, Afshin Akhondzadeh; Hadian, Mojtaba

    2011-02-01

    In the face of emerging new pathogens and ever-growing health-conscious customers, food preservation technology remains on the top agenda of food industry. This study was aimed at determining the effects of the essential oil of Mentha longifolia L., alone and in combination with nisin, on Bacillus cereus and Bacillus subtilis at 8°C and 25°C in a food model (commercial barley soup) during 15 days. The essential oil alone at 8°C inhibited bacterial growth significantly compared with the control (p < 0.05). However, at 25°C, none of the concentrations of the essential oil alone showed inhibitory effect on bacterial growth. At 8°C, the combination effect of the essential oil and nisin on bacteria was noted at 0.25 μg mL(-1) for nisin and 0.05 μL mL(-1) for the essential oil (p < 0.05). The combination of nisin and the essential oil demonstrated significant inhibitory effects on the vegetative forms of bacteria at 25°C, although it was comparable to that of nisin alone at the same concentrations. Electron microscopy studies revealed a great deal of damage to B. cereus treated with a combination of nisin and the essential oil. However, the combination of nisin with the essential oil led to a complete destruction of cell wall and cytoplasm of vegetative cells of B. subtilis.

  9. Mechanism of Trypanosoma brucei gambiense resistance to human serum

    DEFF Research Database (Denmark)

    Uzureau, Pierrick; Uzureau, Sophie; Lecordier, Laurence

    2013-01-01

    The African parasite Trypanosoma brucei gambiense accounts for 97% of human sleeping sickness cases. T. b. gambiense resists the specific human innate immunity acting against several other tsetse-fly-transmitted trypanosome species such as T. b. brucei, the causative agent of nagana disease...... in cattle. Human immunity to some African trypanosomes is due to two serum complexes designated trypanolytic factors (TLF-1 and -2), which both contain haptoglobin-related protein (HPR) and apolipoprotein LI (APOL1). Whereas HPR association with haemoglobin (Hb) allows TLF-1 binding and uptake via......GP), which prevents APOL1 toxicity and induces stiffening of membranes upon interaction with lipids. Two additional features contribute to resistance to TLFs: reduction of sensitivity to APOL1 requiring cysteine protease activity, and TbHpHbR inactivation due to a L210S substitution. According...

  10. Molecular Targets Related Drug Resistance Mechanisms in MDR-, XDR-, and TDR-Mycobacterium tuberculosis Strains

    Directory of Open Access Journals (Sweden)

    H. M. Adnan Hameed

    2018-04-01

    Full Text Available Tuberculosis (TB is a formidable infectious disease that remains a major cause of death worldwide today. Escalating application of genomic techniques has expedited the identification of increasing number of mutations associated with drug resistance in Mycobacterium tuberculosis. Unfortunately the prevalence of bacillary resistance becomes alarming in many parts of the world, with the daunting scenarios of multidrug-resistant tuberculosis (MDR-TB, extensively drug-resistant tuberculosis (XDR-TB and total drug-resistant tuberculosis (TDR-TB, due to number of resistance pathways, alongside some apparently obscure ones. Recent advances in the understanding of the molecular/ genetic basis of drug targets and drug resistance mechanisms have been steadily made. Intriguing findings through whole genome sequencing and other molecular approaches facilitate the further understanding of biology and pathology of M. tuberculosis for the development of new therapeutics to meet the immense challenge of global health.

  11. Effectiveness of Antipseudomonal Antibiotics and Mechanisms of Multidrug Resistance in Pseudomonas aeruginosa.

    Science.gov (United States)

    El ZOWALATYl, Mohamed E; Gyetvaii, Bpla

    2016-01-01

    Pseudomonas aeruginosa is a leading human pathogen that causes serious infections at various tissues and organs leading to life threatening health problems and possible deadly outcomes. Resistance patterns vary widely whether it is from hospitals or community acquired infections. Reporting resistance profiles to a certain antibiotics provide valuable information in a given setting, but may be extrapolated outside the sampling location. In the present study, P. aeruginosa isolates were screened to determine their susceptibilities against anti-pseudomonal antimicrobial agents and possible existing mechanisms of resistance were determined. Eighty-six isolates of P. aeruginosa were recovered. Isolates representing different resistance profiles were screened for the existence of three different resistance mechanisms including drug inactivation due to metallo-β-lactamases, drug impermeability by outer membrane proteins and drug efflux. All tested isolates showed uniform susceptibility (100%, n = 86/86) to piperacillin, meropenem, amikacin, and polymyxin B. A single isolate was found to be imipenem resistant (99%, n = 85/86). The possible mechanisms of resistance of P. aeruginosa to imipenem involve active drug efflux pumps, outer membrane impermeability as well as drug inactivating enzymes. These findings demonstrate the fundamental importance of the in vitro susceptibility testing of antibiotics prior to antipseudomonal therapy and highlight the need for a continuous antimicrobial resistance surveillance programs to monitor the changing resistance patterns so that clinicians and health care officials are updated as to the most effective therapeutic agents to combat the serious outcomes of P. aeruginosa infections.

  12. Development of LRFD resistance factors for mechanically stabilized earth (MSE) walls : [technical summary].

    Science.gov (United States)

    2013-12-01

    Bridge approach embankments and many other : transportation-related applications make use of : reinforced earth retaining structures. Mechanically : Stabilized Earth (MSE) walls are designed under : the Load and Resistance Factor Design (LRFD) : meth...

  13. Mechanism of Action of Substituted Indanones in Multidrug Resistant Breast Cancer

    National Research Council Canada - National Science Library

    Leoni, Lorenzo

    2001-01-01

    ... (Cancer Res 2001 Oct 1;61(19):7248.54) - analyzed the indanocine-resistant stable cell line - identified the potential indanocine-binding site on tubulin - continued the animal testing of indanocine - studies the pro-apoptotic mechanism...

  14. Mechanisms of resistance to chloramphenicol in Pseudomonas putida KT2440.

    Science.gov (United States)

    Fernández, Matilde; Conde, Susana; de la Torre, Jesús; Molina-Santiago, Carlos; Ramos, Juan-Luis; Duque, Estrella

    2012-02-01

    Pseudomonas putida KT2440 is a chloramphenicol-resistant bacterium that is able to grow in the presence of this antibiotic at a concentration of up to 25 μg/ml. Transcriptomic analyses revealed that the expression profile of 102 genes changed in response to this concentration of chloramphenicol in the culture medium. The genes that showed altered expression include those involved in general metabolism, cellular stress response, gene regulation, efflux pump transporters, and protein biosynthesis. Analysis of a genome-wide collection of mutants showed that survival of a knockout mutant in the TtgABC resistance-nodulation-division (RND) efflux pump and mutants in the biosynthesis of pyrroloquinoline (PQQ) were compromised in the presence of chloramphenicol. The analysis also revealed that an ABC extrusion system (PP2669/PP2668/PP2667) and the AgmR regulator (PP2665) were needed for full resistance toward chloramphenicol. Transcriptional arrays revealed that AgmR controls the expression of the pqq genes and the operon encoding the ABC extrusion pump from the promoter upstream of open reading frame (ORF) PP2669.

  15. Differential Resistance Mechanisms to Glyphosate Result in Fitness Cost for Lolium perenne and L. multiflorum

    Directory of Open Access Journals (Sweden)

    Pablo T. Fernández-Moreno

    2017-10-01

    Full Text Available Multiple mechanisms of resistance to glyphosate are exhibited by populations of Lolium spp. worldwide. Association of resistance with growth and reproductive fitness is an important predictor for long-term success of glyphosate-resistant (R versus glyphosate-susceptible (S biotypes. Numerous studies were conducted on R- and S-biotypes of Italian ryegrass (Lolium multiflorum and perennial ryegrass (L. perenne to characterize the underlying mechanism(s of glyphosate resistance and associate this with growth and reproductive fitness. L. perenne expressed both altered uptake and translocation as well as a genetic change at 106-Pro to –Ser, This pattern for two resistance mechanisms is unique. L. multiflorum also exhibited altered uptake and translocation as well as duplication of EPSPS gene copies. Reduced plant biomass and height for R-versus S-biotypes of both species was evident over two growing seasons. This resulted in S- versus R- L. multiflorum producing up to 47 and 38% more seeds in 2014 and 2015, respectively. S- L. perenne produced up to 20 and 30% more seeds in 2014 and 2015, respectively. Both non-target site and target-site mechanisms of glyphosate resistance can render Lolium spp. at a competitive disadvantage. This has long-term implications for the success of glyphosate-resistant plants in the absence of selection pressure.

  16. A review of mechanisms of circumvention and modulation of chemotherapeutic drug resistance.

    Science.gov (United States)

    O'Connor, R

    2009-05-01

    Drug resistance is a serious limitation to the effective treatment of a number of common malignancies. Thirty years of laboratory and clinical research have greatly defined the molecular alterations underlying many drug resistance processes in cancer. Based on this knowledge, strategies to overcome the impact of resistance and increase the efficacy of cancer treatment have been translated from laboratory models to clinical trials. This article reviews laboratory and, in particular, clinical attempts at drug resistance circumvention from early forays in the inhibition of cellular efflux pump-mediated drug resistance through to more selective circumvention agent strategies and into inhibition of the other important mechanisms which can allow cancer cells to survive therapy, such as apoptosis resistance. Despite some promising results to date, resistance inhibition strategies have largely failed due to poor understanding of the pharmacology, dynamics and complexity of the resistance phenotype. With the realisation that new molecularly-targeted agents can also be rendered ineffectual by the actions of resistance mechanisms, a major focus is once again emerging on identifying new strategies/pharmaceuticals which can augment the activity of the arsenal of more conventional cytotoxics and newer targeted anti-cancer drugs. Future tactical directions where old and new resistance strategies may merge to overcome this challenge are discussed.

  17. Molecular epidemiology and mechanisms of carbapenem resistance in Pseudomonas aeruginosa isolates from Chinese hospitals.

    Science.gov (United States)

    Wang, Jie; Zhou, Jian-ying; Qu, Ting-ting; Shen, Ping; Wei, Ze-qing; Yu, Yun-song; Li, Lan-juan

    2010-05-01

    We investigated the molecular epidemiology and carbapenem resistance mechanisms of 258 non-duplicate carbapenem-resistant clinical isolates of Pseudomonas aeruginosa collected from 2006 to 2007 at 28 hospitals in China. Up to 88% of the carbapenem-resistant isolates were multidrug-resistant. Pulsed-field gel electrophoresis (PFGE) revealed that levels of intrahospital and interhospital dissemination of clones were low. To assess the mechanisms leading to resistance, all 258 carbapenem-resistant isolates were analysed for expression of the chromosomal beta-lactamase (AmpC), the porin important for entry of carbapenems (OprD) and an efflux system (MexAB-OprM) known to extrude some beta-lactams. Carbapenem resistance was driven mainly by mutational inactivation of OprD, accompanied or not by hyperexpression of AmpC or MexAB-OprM. Metallo-beta-lactamase genes were detected in 22 carbapenem-resistant isolates in China, belonging to eight pulsotypes. The bla(OXA-50) gene was detected among all of the carbapenem-resistant isolates, whereas the bla(GES-5) gene was detected in only one carbapenem-resistant isolate. Copyright 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.

  18. Mechanisms of Invasion Resistance of Aquatic Plant Communities

    Science.gov (United States)

    Petruzzella, Antonella; Manschot, Johan; van Leeuwen, Casper H. A.; Grutters, Bart M. C.; Bakker, Elisabeth S.

    2018-01-01

    Invasive plant species are among the major threats to freshwater biodiversity. Few experimental studies have investigated whether native plant diversity can provide biotic resistance to invaders in freshwater ecosystems. At small spatial scales, invasion resistance may increase with plant species richness due to a better use of available resources, leaving less available for a potential invader (Complementarity effect) and/or the greater probability to have a highly competitive (or productive) native species in the community (Selection effect). In submerged aquatic plant communities, we tested the following hypotheses: (1) invader establishment success is greatest in the absence of a native plant community; (2) lower in plant communities with greater native species richness, due to complementary and/or selection effects; and (3) invader establishment success would be lowest in rooted plant communities, based on the limiting similarity theory as the invader is a rooted submerged species. In a greenhouse experiment, we established mesocosms planted with 0 (bare sediment), 1, 2, and 4 submerged plant species native to NW Europe and subjected these to the South African invader Lagarosiphon major (Ridl.) Moss. We used two rooted (Myriophyllum spicatum L., Potamogeton perfoliatus L.) and two non-rooted native species (Ceratophyllum demersum L., Utricularia vulgaris L.) representing two distinct functional groups considering their nutrient acquisition strategy which follows from their growth form, with, respectively, the sediment and water column as their main nutrient source. We found that the presence of native vegetation overall decreased the establishment success of an alien aquatic plant species. The strength of this observed biotic resistance increased with increasing species richness of the native community. Mainly due to a selection effect, the native biomass of mixed communities overyielded, and this further lowered the establishment success of the invader in our

  19. The molecular changing mechanism of Ampicillin-Sulbactam resistant Staphylococcus aureus towards Methicillin resistant Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Mieke Hemiawati Satari

    2005-12-01

    Full Text Available The aim of this study was to determine the molecular changing of S.aureus, which is resistant to Ampicillin-Sulbactam and then become resistant to Methicillin as a result of improper dosage. The study was conducted by isolating Ampicillin-Sulbactam resistant and Methicillin Resistant S.aureus (MRSA, afterwards an amplification process was performed by PCR (Polymerase Chain Reaction. to isolate the betalactamase enzyme regulator and PBP 2a genes. The result of this research showed that there were a deletion of few amino acids from the regulator gene, and a suspicion that the DNA sequence had been substituted from PBP 2 gene into PBP 2a (gen mec. This process had formed MRSA.

  20. Fibril morphology and tendon mechanical properties in patellar tendinopathy: effects of heavy slow resistance training

    DEFF Research Database (Denmark)

    Kongsgaard, Mads; Qvortrup, Klaus; Larsen, Jytte Overgaard

    2010-01-01

    BACKGROUND: Patellar tendinopathy is characterized by pathologic abnormalities. Heavy slow resistance training (HSR) is effective in the management of patellar tendinopathy, but the underlying functional mechanisms remain elusive. PURPOSE: To investigate fibril morphology and mechanical properties...... area. Heavy slow resistance training improved the clinical outcome of patellar tendinopathy, and these improvements were associated with normalization of fibril morphology, most likely due to a production of new fibrils....

  1. Dissecting the Mechanisms of Drug Resistance in BRCA1/2-Mutant Breast Cancers

    Science.gov (United States)

    2017-10-01

    AWARD NUMBER: W81XWH-16-1-0600 TITLE: Dissecting the Mechanisms of Drug Resistance in BRCA1/2-Mutant Breast Cancers PRINCIPAL INVESTIGATOR: Dr...2017 4. TITLE AND SUBTITLE Dissecting the Mechanisms of Drug Resistance in BRCA1/2- Mutant Breast Cancers 5a. CONTRACT NUMBER W81XWH-16-1-0600 5b...therapeutic modality for targeting homologous recombination (HR) deficient tumors such as BRCA1 and BRCA2-mutated triple negative breast cancers

  2. Production of sintered alumina from powder; optimization of the sinterized parameters for the maximum mechanical resistence

    International Nuclear Information System (INIS)

    Rocha, J.C. da.

    1981-02-01

    Pure, sinterized alumina and the optimization of the parameters of sinterization in order to obtain the highest mechanical resistence are discussed. Test materials are sinterized from a fine powder of pure alumina (Al 2 O 3 ), α phase, at different temperatures and times, in air. The microstructures are analysed concerning porosity and grain size. Depending on the temperature or the time of sinterization, there is a maximum for the mechanical resistence. (A.R.H.) [pt

  3. Thiamethoxam Resistance in the House Fly, Musca domestica L.: Current Status, Resistance Selection, Cross-Resistance Potential and Possible Biochemical Mechanisms.

    Directory of Open Access Journals (Sweden)

    Hafiz Azhar Ali Khan

    Full Text Available The house fly, Musca domestica L., is an important ectoparasite with the ability to develop resistance to insecticides used for their control. Thiamethoxam, a neonicotinoid, is a relatively new insecticide and effectively used against house flies with a few reports of resistance around the globe. To understand the status of resistance to thiamethoxam, eight adult house fly strains were evaluated under laboratory conditions. In addition, to assess the risks of resistance development, cross-resistance potential and possible biochemical mechanisms, a field strain of house flies was selected with thiamethoxam in the laboratory. The results revealed that the field strains showed varying level of resistance to thiamethoxam with resistance ratios (RR at LC50 ranged from 7.66-20.13 folds. Continuous selection of the field strain (Thia-SEL for five generations increased the RR from initial 7.66 fold to 33.59 fold. However, resistance declined significantly when the Thia-SEL strain reared for the next five generations without exposure to thiamethoxam. Compared to the laboratory susceptible reference strain (Lab-susceptible, the Thia-SEL strain showed cross-resistance to imidacloprid. Synergism tests revealed that S,S,S-tributylphosphorotrithioate (DEF and piperonyl butoxide (PBO produced synergism of thiamethoxam effects in the Thia-SEL strain (2.94 and 5.00 fold, respectively. In addition, biochemical analyses revealed that the activities of carboxylesterase (CarE and mixed function oxidase (MFO in the Thia-SEL strain were significantly higher than the Lab-susceptible strain. It seems that metabolic detoxification by CarE and MFO was a major mechanism for thiamethoxam resistance in the Thia-SEL strain of house flies. The results could be helpful in the future to develop an improved control strategy against house flies.

  4. A common mechanism of clinical HIV-1 resistance to the CCR5 antagonist maraviroc despite divergent resistance levels and lack of common gp120 resistance mutations.

    Science.gov (United States)

    Roche, Michael; Salimi, Hamid; Duncan, Renee; Wilkinson, Brendan L; Chikere, Kelechi; Moore, Miranda S; Webb, Nicholas E; Zappi, Helena; Sterjovski, Jasminka; Flynn, Jacqueline K; Ellett, Anne; Gray, Lachlan R; Lee, Benhur; Jubb, Becky; Westby, Mike; Ramsland, Paul A; Lewin, Sharon R; Payne, Richard J; Churchill, Melissa J; Gorry, Paul R

    2013-04-20

    The CCR5 antagonist maraviroc (MVC) inhibits human immunodeficiency virus type 1 (HIV-1) entry by altering the CCR5 extracellular loops (ECL), such that the gp120 envelope glycoproteins (Env) no longer recognize CCR5. The mechanisms of HIV-1 resistance to MVC, the only CCR5 antagonist licensed for clinical use are poorly understood, with insights into MVC resistance almost exclusively limited to knowledge obtained from in vitro studies or from studies of resistance to other CCR5 antagonists. To more precisely understand mechanisms of resistance to MVC in vivo, we characterized Envs isolated from 2 subjects who experienced virologic failure on MVC. Envs were cloned from subjects 17 and 24 before commencement of MVC (17-Sens and 24-Sens) and after virologic failure (17-Res and 24-Res). The Envs cloned during virologic failure showed broad divergence in resistance levels, with 17-Res Env exhibiting a relatively high maximal percent inhibition (MPI) of ~90% in NP2-CD4/CCR5 cells and peripheral blood mononuclear cells (PBMC), and 24-Res Env exhibiting a very low MPI of ~0 to 12% in both cell types, indicating relatively "weak" and "strong" resistance, respectively. Resistance mutations were strain-specific and mapped to the gp120 V3 loop. Affinity profiling by the 293-Affinofile assay and mathematical modeling using VERSA (Viral Entry Receptor Sensitivity Analysis) metrics revealed that 17-Res and 24-Res Envs engaged MVC-bound CCR5 inefficiently or very efficiently, respectively. Despite highly divergent phenotypes, and a lack of common gp120 resistance mutations, both resistant Envs exhibited an almost superimposable pattern of dramatically increased reliance on sulfated tyrosine residues in the CCR5 N-terminus, and on histidine residues in the CCR5 ECLs. This altered mechanism of CCR5 engagement rendered both the resistant Envs susceptible to neutralization by a sulfated peptide fragment of the CCR5 N-terminus. Clinical resistance to MVC may involve divergent Env

  5. Nucleus geometry and mechanical properties of resistance spot ...

    Indian Academy of Sciences (India)

    Department of Mechanical Engineering, Engineering Faculty, Mersin University, 33343 Ciftlikkoy, Mersin, Turkey; Metallurgy Materials Engineering Department, Engineering Faculty, Karabuk University Baliklarkayasi, Karabuk, Turkey; Faculty of Tarsus Technical Education, Mersin University, 33480 Tarsus, Turkey ...

  6. [Fluoroquinolones in ophthalmology: mechanisms of action and resistance].

    Science.gov (United States)

    Labetoulle, M; Chiquet, C

    2008-10-01

    The arrival of fluoroquinolones in the 1980s aroused enormous enthusiasm in the medical community, justified by the spectrum of antibacterial activity, good tolerance, and wide distribution in tissues, even after oral administration. However, the extensive use of these new antibiotiques finally ended in emerging resistance, which limits the efficiency of all the molecules in the class, including those that have appeared in the last few years. Ocular diseases also benefited from the emergence of fluoroquinolones, notably for topical treatments. It is now mandatory to adapt the prescriptions to the best indications, in order to protect the vast therapeutic potential of these molecules.

  7. VirR-Mediated Resistance of Listeria monocytogenes against Food Antimicrobials and Cross-Protection Induced by Exposure to Organic Acid Salts.

    Science.gov (United States)

    Kang, Jihun; Wiedmann, Martin; Boor, Kathryn J; Bergholz, Teresa M

    2015-07-01

    Formulations of ready-to-eat (RTE) foods with antimicrobial compounds constitute an important safety measure against foodborne pathogens such as Listeria monocytogenes. While the efficacy of many commercially available antimicrobial compounds has been demonstrated in a variety of foods, the current understanding of the resistance mechanisms employed by L. monocytogenes to counteract these stresses is limited. In this study, we screened in-frame deletion mutants of two-component system response regulators associated with the cell envelope stress response for increased sensitivity to commercially available antimicrobial compounds (nisin, lauric arginate, ε-polylysine, and chitosan). A virR deletion mutant showed increased sensitivity to all antimicrobials and significantly greater loss of membrane integrity when exposed to nisin, lauric arginate, or ε-polylysine (P food antimicrobials. Further, the potential for cross-protection induced by other food-related stresses (e.g., organic acids) needs to be considered when applying these novel food antimicrobials as a hurdle strategy for RTE foods. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  8. Activation and Transfer of the Chromosomal Phage Resistance Mechanism AbiV in Lactococcus lactis

    DEFF Research Database (Denmark)

    Haaber, J.; Moineau, S.; Hammer, Karin

    2009-01-01

    AbiV is a chromosomally encoded phage resistance mechanism that is silent in the wild-type phage-sensitive strain Lactococcus lactis subsp. cremoris MG1363. Spontaneous phage-resistant mutants of L. lactis MG1363 were analyzed by reverse transcriptase PCR and shown to express AbiV. This expression...... was related to a reorganization in the upstream region of abiV. Transfer of abiV between two lactococcal strains, most likely by conjugation, was also demonstrated. To our knowledge, this is the first report of natural transfer of a chromosomally encoded phage resistance mechanism....

  9. Genomic sequencing of a strain of Acinetobacter baumannii and potential mechanisms to antibiotics resistance.

    Science.gov (United States)

    Zhao, Lei; Li, Hongru; Zhu, Ziwen; Wakefield, Mark R; Fang, Yujiang; Ye, Ying

    2017-06-01

    Acinetobacter baumannii has been becoming a great challenge to clinicians due to their resistance to almost all available antibiotics. In this study, we sequenced the genome from a multiple antibiotics resistant Acinetobacter baumannii stain which was named A. baumannii-1isolated from China by SMRT sequencing technology to explore its potential mechanisms to antibiotic resistance. We found that several mechanisms might contribute to the antibiotic resistance of Acinetobacter baumannii. Specifically, we found that SNP in genes associated with nucleotide excision repair and ABC transporter might contribute to its resistance to multiple antibiotics; we also found that specific genes associated with bacterial DNA integration and recombination, DNA-mediated transposition and response to antibiotics might contribute to its resistance to multiple antibiotics; Furthermore, specific genes associated with penicillin and cephalosporin biosynthetic pathway and specific genes associated with CHDL and MBL β-lactamase genes might contribute to its resistance to multiple antibiotics. Thus, the detailed mechanisms by which Acinetobacter baumannii show extensive resistance to multiple antibiotics are very complicated. Such a study might be helpful to develop new strategies to control Acinetobacter baumannii infection. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. [Advances in molecular mechanisms of bacterial resistance caused by stress-induced transfer of resistance genes--a review].

    Science.gov (United States)

    Sun, Dongchang; Wang, Bing; Zhu, Lihong

    2013-07-04

    The transfer of resistance gene is one of the most important causes of bacterial resistance. Recent studies reveal that stresses induce the transfer of antibiotic resistance gene through multiple mechanisms. DNA damage stresses trigger bacterial SOS response and induce the transfer of resistance gene mediated by conjugative DNA. Antibiotic stresses induce natural bacterial competence for transformation in some bacteria which lack the SOS system. In addition, our latest studies show that the general stress response regulator RpoS regulates a novel type of resistance gene transfer which is mediated by double-stranded plasmid DNA and occurs exclusively on the solid surface. In this review, we summarized recent advances in SOS dependent and independent stress-induced DNA transfer which is mediated by conjugation and transformation respectively, and the transfer of double-stranded plasmid DNA on the solid surface which is regulated by RpoS. We propose that future work should address how stresses activate the key regulators and how these regulators control the expression of gene transfer related genes. Answers to the above questions would pave the way for searching for candidate targets for controlling bacterial resistance resulted from the transfer of antibiotic genes.

  11. Mechanisms and management of diuretic resistance in congestive heart failure.

    Science.gov (United States)

    De Bruyne, L K M

    2003-05-01

    Diuretic drugs are used almost universally in patients with congestive heart failure, most frequently the potent loop diuretics. Despite their unproven effect on survival, their indisputable efficacy in relieving congestive symptoms makes them first line therapy for most patients. In the treatment of more advanced stages of heart failure diuretics may fail to control salt and water retention despite the use of appropriate doses. Diuretic resistance may be caused by decreased renal function and reduced and delayed peak concentrations of loop diuretics in the tubular fluid, but it can also be observed in the absence of these pharmacokinetic abnormalities. When the effect of a short acting diuretic has worn off, postdiuretic salt retention will occur during the rest of the day. Chronic treatment with a loop diuretic results in compensatory hypertrophy of epithelial cells downstream from the thick ascending limb and consequently its diuretic effect will be blunted. Strategies to overcome diuretic resistance include restriction of sodium intake, changes in dose, changes in timing, and combination diuretic therapy.

  12. Interplay between mutational and horizontally acquired resistance mechanisms and its association with carbapenem resistance amongst extensively drug-resistant Pseudomonas aeruginosa (XDR-PA).

    Science.gov (United States)

    Shu, Jwu-Ching; Chia, Ju-Hsin; Siu, Leung-Kei; Kuo, An-Jing; Huang, Shu-Huan; Su, Lin-Hui; Wu, Tsu-Lan

    2012-03-01

    Between 2003 and 2009, the prevalence of extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) increased significantly in northern Taiwan from 1.0% to 2.1%. Molecular methods were used to investigate the genetic relatedness and carbapenem resistance mechanisms of a collection of 203 non-repetitive XDR-PA isolates available for study. Using pulsed-field gel electrophoresis (PFGE), 52 genotypes were observed; one predominant genotype (pulsotype 1) was found in 57.6% of the isolates. Polymerase chain reaction (PCR), sequencing and quantitative reverse-transcriptase PCR analyses demonstrated that one horizontally acquired mechanism [metallo-β-lactamase (MBL) genes] and two mutational mechanisms (efflux and porins) accounted for the carbapenem resistance. The most predominant horizontally acquired mechanism was carriage of bla(VIM-3), which was found in 61.1% of isolates. Decreased expression of oprD was the most prevalent mutational mechanism and was found in 70.0% of the XDR-PA isolates, whereas overexpression of mexA was found in 27.6% of the isolates. The highlight of this study was the discovery of statistically significant relationships between certain horizontally acquired and mutational resistance mechanisms and their contribution to carbapenem susceptibility. MBL-producers expressed significantly lower MexAB and higher OprD than non-MBL-producers. Amongst isolates without an acquired β-lactamase gene, oprD expression was significantly reduced, whilst expression of efflux pumps was increased. Reduced OprD expression alone or the production of VIM-type MBLs showed similar contributions to a low to intermediate MIC(50) (minimum inhibitory concentration for 50% of the organisms) for carbapenems. Isolates with reduced OprD expression that simultaneously harboured bla(VIM) exhibited high levels of resistance to carbapenems, which implied that these two mechanisms had a synergistic effect on the MICs. Copyright © 2011 Elsevier B.V. and the International

  13. Mechanism of Action and Resistance to Daptomycin in Staphylococcus aureus and Enterococci.

    Science.gov (United States)

    Miller, William R; Bayer, Arnold S; Arias, Cesar A

    2016-11-01

    Lipopeptides are natural product antibiotics that consist of a peptide core with a lipid tail with a diverse array of target organisms and mechanisms of action. Daptomycin (DAP) is an example of these compounds with specific activity against Gram-positive organisms. DAP has become increasingly important to combat infections caused by Gram-positive bacteria because of the presence of multidrug resistance in these organisms, particularly in methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE). However, emergence of resistance to DAP during therapy is a well-described phenomenon that threatens the clinical use of this antibiotic, limiting further the therapeutic options against both MRSA and VRE. This work will review the historical aspects of the development of DAP, as well as the current knowledge on its mechanism of action and pathways to resistance in a clinically relevant context. Copyright © 2016 Cold Spring Harbor Laboratory Press; all rights reserved.

  14. Co-expression of Nisin Z and Leucocin C as a Basis for Effective Protection Againstin Pasteurized Milk

    NARCIS (Netherlands)

    Fu, Yuxin; Mu, Dongdong; Qiao, Wanjin; Zhu, Duolong; Wang, Xiangxiang; Liu, Fulu; Xu, Haijin; Saris, Per; Kuipers, Oscar P; Qiao, Mingqiang

    2018-01-01

    Nisin, an important bacteriocin fromLactococcus lactissubsp., is primarily active against various Gram-positive bacteria. Leucocin C, produced byLeuconostoc carnosum4010, is a class IIa bacteriocin used to inhibit the growth ofListeria monocytogenes.Because two bacteriocins have different modes of

  15. Potential aquaculture probiont Lactococcus lactis TW34 produces nisin Z and inhibits the fish pathogen Lactococcus garvieae.

    Science.gov (United States)

    Sequeiros, Cynthia; Garcés, Marisa E; Vallejo, Marisol; Marguet, Emilio R; Olivera, Nelda L

    2015-04-01

    Bacteriocin-producing Lactococcus lactis TW34 was isolated from marine fish. TW34 bacteriocin inhibited the growth of the fish pathogen Lactococcus garvieae at 5 AU/ml (minimum inhibitory concentration), whereas the minimum bactericidal concentration was 10 AU/ml. Addition of TW34 bacteriocin to L. garvieae cultures resulted in a decrease of six orders of magnitude of viable cells counts demonstrating a bactericidal mode of action. The direct detection of the bacteriocin activity by Tricine-SDS-PAGE showed an active peptide with a molecular mass ca. 4.5 kDa. The analysis by MALDI-TOF-MS detected a strong signal at m/z 2,351.2 that corresponded to the nisin leader peptide mass without the initiating methionine, whose sequence STKDFNLDLVSVSKKDSGASPR was confirmed by MS/MS. Sequence analysis of nisin structural gene confirmed that L. lactis TW34 was a nisin Z producer. This nisin Z-producing strain with probiotic properties might be considered as an alternative in the prevention of lactococcosis, a global disease in aquaculture systems.

  16. Insecticide resistance is mediated by multiple mechanisms in recently introduced Aedes aegypti from Madeira Island (Portugal).

    Science.gov (United States)

    Seixas, Gonçalo; Grigoraki, Linda; Weetman, David; Vicente, José Luís; Silva, Ana Clara; Pinto, João; Vontas, John; Sousa, Carla Alexandra

    2017-07-01

    Aedes aegypti is a major mosquito vector of arboviruses, including dengue, chikungunya and Zika. In 2005, Ae. aegypti was identified for the first time in Madeira Island. Despite an initial insecticide-based vector control program, the species expanded throughout the Southern coast of the island, suggesting the presence of insecticide resistance. Here, we characterized the insecticide resistance status and the underlying mechanisms of two populations of Ae. aegypti from Madeira Island, Funchal and Paúl do Mar. WHO susceptibility bioassays indicated resistance to cyfluthrin, permethrin, fenitrothion and bendiocarb. Use of synergists significantly increased mortality rates, and biochemical assays indicated elevated activities of detoxification enzymes, suggesting the importance of metabolic resistance. Microarray-based transcriptome analysis detected significant upregulation in both populations of nine cytochrome P450 oxidase genes (including four known pyrethroid metabolizing enzymes), the organophosphate metabolizer CCEae3a, Glutathione-S-transferases, and multiple putative cuticle proteins. Genotyping of knockdown resistance loci linked to pyrethroid resistance revealed fixation of the 1534C mutation, and presence with moderate frequencies of the V1016I mutation in each population. Significant resistance to three major insecticide classes (pyrethroid, carbamate and organophosphate) is present in Ae. aegypti from Madeira Island, and appears to be mediated by multiple mechanisms. Implementation of appropriate resistance management strategies including rotation of insecticides with alternative modes of action, and methods other than chemical-based vector control are strongly advised to delay or reverse the spread of resistance and achieve efficient control.

  17. New insights into Vinca alkaloids resistance mechanism and circumvention in lung cancer.

    Science.gov (United States)

    Zhang, Ying; Yang, Shao-Hui; Guo, Xiu-Li

    2017-12-01

    Nowadays, lung cancer, as a health problem in worldwide, has high mortality both in men and women. Despite advances in diagnosis and surgical techniques of lung cancer in recent decades, chemotherapy is still a fundamentally and extensively useful strategy. Vinca alkaloids are a class of important and widely used drugs in the treatment of lung cancer, targeting on the Vinca binding site at the exterior of microtubule plus ends. Either intrinsic or acquired resistance to chemotherapy of Vinca alkaloids has been a major obstacle to the treatment of lung cancer, which arose great interests in studies of understanding and overcoming resistance. In this review, we focused on the application and resistance mechanisms of the Vinca alkaloids such as vinblastine, vincristine, vinorelbine and vinflunine in lung cancer. We reviewed characteristic resistance mechanisms in lung cancer including over-expression of ATP-binding cassette (ABC) transporters P-glycoprotein and structural, functional or expression alterations of β-tubulin (βII, βIII, βIV) which may devote to the development of acquired resistance to the Vinca alkaloids; multidrug-resistance proteins (MRP1, MRP2, MRP3) and RLIP76 protein have also been identified that probably play a significant role in intrinsic resistance. Lung resistance-related protein (LRP) is contributed to lung cancer therapy resistance, but is not deal with the Vinca alkaloids resistance in lung cancer. Understanding the principle of the Vinca alkaloids in clinical application and mechanisms of drug resistance will support individualized lung cancer therapy and improve future therapies. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  18. [Carbapenem resistance in Pseudomonas aeruginosa isolates: an example of interaction between different mechanisms].

    Science.gov (United States)

    Santella, Gisela; Pollini, Simona; Docquier, Jean-Denis; Almuzara, Marisa; Gutkind, Gabriel; Rossolini, Gian Maria; Radice, Marcela

    2011-12-01

    To identify the outer membrane protein absent in the resistant isolates and to determine both the causes of its absence in the membrane and the presence of other mechanisms of carbapenem resistance in clinical isolates of Pseudomonas aeruginosa. Twenty isolates from an outbreak of P. aeruginosa previously characterized as metallo-beta-lactamase IMP-13 producers were studied. All the isolates exhibited equal expression of the IMP-13 enzyme, but only five of them were carbapenem-resistant. It was found that the five resistant isolates lacked a outer membrane protein. The oprD and ampC genes were sequenced; the outer membrane proteins were identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry; the OprD and AmpC expressions, as well as the Mex efflux system, were assessed by real-time polymerase chain reaction; and finally, the contribution of reduced OprD to carbapenem resistance was determined. The absent outer membrane protein in group R was identified as OprD-TS; however, no variations in its expression were observed. The oprD gene presented mutations in the five resistant isolates. The production of AmpC PDC-5-type enzyme and the MexAB-OprM efflux system was the same in both carbapenem-sensitive and -resistant isolates. The contribution of the combined presence of IMP-13 and reduced OprD to increased resistance was examined. Different mechanisms contribute to carbapenem resistance in IMP-13-producing isolates. The possibility that these IMP-13-producing isolates could go undetected poses a latent risk when selecting mutants with added resistance mechanisms in order to enhance carbapenem resistance.

  19. Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes.

    Science.gov (United States)

    Poirel, Laurent; Jayol, Aurélie; Nordmann, Patrice

    2017-04-01

    SUMMARYPolymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria. Susceptibility testing is challenging with polymyxins, and currently available techniques are presented here. Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented. This review also presents recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyxin resistance determinant MCR-1. Epidemiological features summarizing the current knowledge in that field are presented. Copyright © 2017 American Society for Microbiology.

  20. The model of mechanisms of materials resistance to fracture

    International Nuclear Information System (INIS)

    Tyugashov, P.F.

    1994-01-01

    A description is made for shear, break-up and combined fracture mechanisms. The potentiality of the model proposed is demonstrated on study of load-elongation diagram for titanium alloy type VT3-1. Comparison of calculation result to with available experimental data confirms the validity of assumptions about materials behaviour under creep conditions. 3 refs., 3 tabs

  1. Nucleus geometry and mechanical properties of resistance spot ...

    Indian Academy of Sciences (India)

    ‡Faculty of Tarsus Technical Education, Mersin University, 33480 Tarsus, Turkey. MS received 10 April 2012; revised 5 July 2012. Abstract. In this study, mechanical ... Depending on the weld current and time, effects of zinc coating on tensile properties, microhardness values as well as microstructure nugget geometry and ...

  2. Lincosamides: Chemical structure, biosynthesis, mechanism of action, resistance, and applications

    Czech Academy of Sciences Publication Activity Database

    Spížek, Jaroslav; Řezanka, Tomáš

    2017-01-01

    Roč. 133, June 1 SI (2017), s. 20-28 ISSN 0006-2952 Institutional support: RVO:61388971 Keywords : Lincosamides * Chemical structure * Biosynthesis and mechanism of action Subject RIV: EE - Microbiology, Virology OBOR OECD: Microbiology Impact factor: 4.581, year: 2016

  3. A mechanism of acquired resistance to complement-mediated lysis by Entamoeba histolytica.

    Science.gov (United States)

    Gutiérrez-Kobeh, L; Cabrera, N; Pérez-Montfort, R

    1997-04-01

    Some Entamoeba histolytica strains resist complement-mediated lysis by serum. Susceptible and resistant strains activate the complement system equivalently, but resistant amebas evade killing by membrane attack complexes. Our objective was to determine the mechanism by which trophozoites of E. histolytica resist lysis by human serum. Amebas were made resistant to lysis by incubation with increasing concentrations of normal human serum. The possibility that resistant cells ingest membrane attack complexes was explored by subcellular fractionation of susceptible and resistant trophozoites treated with sublytic concentrations of human serum containing radiolabeled C9. In both cases, most of the label was in the fractions containing plasma membrane. The susceptible strain consistently showed more label associated with these fractions than the resistant strain. Thus, the possibility that the membrane attack complexes were released to the medium was explored. Both resistant and susceptible trophozoites release to the medium similar amounts of material excluded by Sepharose CL-2B in the presence or absence of normal human serum. Labeled C9 elutes together with the main bulk of proteins from the medium: this indicates that it is not in vesicles or high molecular weight aggregates. Coincubation of susceptible amebas with lysates of resistant trophozoites confers resistance to susceptible cells within 30 min. Resistance to lysis by serum can also be acquired by susceptible amebas after coincubation with lysates from human erythrocytes or after feeding them with whole human red blood cells. Resistant but not susceptible trophozoites show intense immunofluorescent staining on their surface with anti-human erythrocytic membrane antibody. These results suggest that amebas acquire resistance to lysis by serum by incorporating into their membranes complement regulatory proteins.

  4. Molecular mechanisms associated with Fluconazole resistance in clinical Candida albicans isolates from India.

    Science.gov (United States)

    Mane, Arati; Vidhate, Pallavi; Kusro, Chanchal; Waman, Vaishali; Saxena, Vandana; Kulkarni-Kale, Urmila; Risbud, Arun

    2016-02-01

    Resistance to azole antifungals is a significant problem in Candida albicans. An understanding of resistance at molecular level is essential for the development of strategies to tackle resistance and rationale design of newer antifungals and target-based molecular approaches. This study presents the first evaluation of molecular mechanisms associated with fluconazole resistance in clinical C.albicans isolates from India. Target site (ERG11) alterations were determined by DNA sequencing, whereas real-time PCRs were performed to quantify target and efflux pump genes (CDR1, CDR2, MDR1) in 87 [Fluconazole susceptible (n = 30), susceptible-dose dependent (n = 30) and resistant (n = 27)] C.albicans isolates. Cross-resistance to fluconazole, ketoconazole and itraconazole was observed in 74.1% isolates. Six amino acid substitutions were identified, including 4 (E116D, F145L, E226D, I437V) previously reported ones and 2 (P406L, Q474H) new ones. CDR1 over-expression was seen in 77.7% resistant isolates. CDR2 was exclusively expressed with CDR1 and their concomitant over-expression was associated with azole cross-resistance. MDR1 and ERG11 over-expression did not seem to be associated with resistance. Our results show that drug efflux mediated by Adenosine-5'-triphosphate (ATP)-binding cassette transporters, especially CDR1 is the predominant mechanism of fluconazole resistance and azole cross-resistance in C. albicans and indicate the need for research directed towards developing strategies to tackle efflux mediated resistance to salvage azoles. © 2015 Blackwell Verlag GmbH.

  5. Reduced expression of p27 is a novel mechanism of docetaxel resistance in breast cancer cells

    International Nuclear Information System (INIS)

    Brown, Iain; Shalli, Kawan; McDonald, Sarah L; Moir, Susan E; Hutcheon, Andrew W; Heys, Steven D; Schofield, Andrew C

    2004-01-01

    Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Breast cancers can have an inherent or acquired resistance to docetaxel but the causes of this resistance remain unclear. However, apoptosis and cell cycle regulation are key mechanisms by which most chemotherapeutic agents exert their cytotoxic effects. We created two docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) and performed cDNA microarray analysis to identify candidate genes associated with docetaxel resistance. Gene expression changes were validated at the RNA and protein levels by reverse transcription PCR and western analysis, respectively. Gene expression cDNA microarray analysis demonstrated reduced p27 expression in docetaxel-resistant breast cancer cells. Although p27 mRNA expression was found to be reduced only in MCF-7 docetaxel-resistant sublines (2.47-fold), reduced expression of p27 protein was noted in both MCF-7 and MDA-MB-231 docetaxel-resistant breast cancer cells (2.83-fold and 3.80-fold, respectively). This study demonstrates that reduced expression of p27 is associated with acquired resistance to docetaxel in breast cancer cells. An understanding of the genes that are involved in resistance to chemotherapy may allow further development in modulating drug resistance, and may permit selection of those patients who are most likely to benefit from such therapies

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

    Directory of Open Access Journals (Sweden)

    Gabriel G Perron

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

  7. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  9. The mechanics of tessellations - bioinspired strategies for fracture resistance.

    Science.gov (United States)

    Fratzl, Peter; Kolednik, Otmar; Fischer, F Dieter; Dean, Mason N

    2016-01-21

    Faced with a comparatively limited palette of minerals and organic polymers as building materials, evolution has arrived repeatedly on structural solutions that rely on clever geometric arrangements to avoid mechanical trade-offs in stiffness, strength and flexibility. In this tutorial review, we highlight the concept of tessellation, a structural motif that involves periodic soft and hard elements arranged in series and that appears in a vast array of invertebrate and vertebrate animal biomaterials. We start from basic mechanics principles on the effects of material heterogeneities in hypothetical structures, to derive common concepts from a diversity of natural examples of one-, two- and three-dimensional tilings/layerings. We show that the tessellation of a hard, continuous surface - its atomization into discrete elements connected by a softer phase - can theoretically result in maximization of material toughness, with little expense to stiffness or strength. Moreover, the arrangement of soft/flexible and hard/stiff elements into particular geometries can permit surprising functions, such as signal filtering or 'stretch and catch' responses, where the constrained flexibility of systems allows a built-in safety mechanism for ensuring that both compressive and tensile loads are managed well. Our analysis unites examples ranging from exoskeletal materials (fish scales, arthropod cuticle, turtle shell) to endoskeletal materials (bone, shark cartilage, sponge spicules) to attachment devices (mussel byssal threads), from both invertebrate and vertebrate animals, while spotlighting success and potential for bio-inspired manmade applications.

  10. Characterization of fecal vancomycin-resistant enterococci with acquired and intrinsic resistance mechanisms in wild animals, Spain.

    Science.gov (United States)

    Lozano, Carmen; Gonzalez-Barrio, David; Camacho, Maria Cruz; Lima-Barbero, Jose Francisco; de la Puente, Javier; Höfle, Ursula; Torres, Carmen

    2016-11-01

    The objectives were to evaluate the presence of vancomycin-resistant enterococci with acquired (VRE-a) and intrinsic (VRE-i) resistance mechanisms in fecal samples from different wild animals, and analyze their phenotypes and genotypes of antimicrobial resistance. A total of 348 cloacal/rectal samples from red-legged partridges (127), white storks (81), red kites (59), and wild boars (81) (June 2014/February 2015) were inoculated in Slanetz-Bartley agar supplemented with vancomycin (4 μg/mL). We investigated the susceptibility to 12 antimicrobials and the presence of 19 antimicrobial resistance and five virulence genes. In addition, we performed multilocus sequence typing, detection of IS16 and studied Tn1546 structure. One VRE-a isolate was identified in one wild boar. This isolate was identified as Enterococcus faecium, harbored vanA gene included into Tn1546 (truncated with IS1542/IS1216), and belonged to the new ST993. This isolate contained the erm(A), erm(B), tet(M), dfrG, and dfrK genes. Neither element IS16 nor the studied virulence genes were detected. Ninety-six VRE-i isolates were identified (89 Enterococcus gallinarum and seven Enterococcus casseliflavus), with the following prevalence: red kites (71.2 %), white storks (46.9 %), red-legged partridges (7.9 %), and wild boars (4.9 %). Most E. gallinarum isolates showed resistance to tetracycline (66.3 %) and/or erythromycin (46.1 %). High-level resistance to aminoglycosides was present among our VRE-i isolates: kanamycin (22.9 %), streptomycin (11.5 %), and gentamicin (9.4 %). In general, VRE-i isolates of red kites showed higher rates of resistance for non-glycopeptide agents than those of other animal species. The dissemination of acquired resistance mechanisms in natural environments could have implications in the global spread of resistance with public health implications.

  11. The Mechanisms of Maize Resistance to Fusarium verticillioides by comprehensive analysis of RNA-seq Data

    Directory of Open Access Journals (Sweden)

    Yanping Wang

    2016-11-01

    Full Text Available Fusarium verticillioides is the most commonly reported fungal species responsible for ear rot of maize which substantially reduces grain yield. It also results in a substantial accumulation of mycotoxins that give rise to toxic response when ingested by animals and humans. For inefficient control by chemical and agronomic measures, it thus becomes more desirable to select more resistant varieties. However, the molecular mechanisms underlying the infection process remain poorly understood, which hampers the application of quantitative resistance in breeding programs. Here, we reveal the disease-resistance mechanism of the maize inbred line of BT-1 which displays high resistance to ear rot using RNA high throughput sequencing. By analyzing RNA-seq data from the BT-1 kernels before and after F. verticillioides inoculation, we found that transcript levels of genes associated with key pathways are dramatically changed compared with the control treatment. Differential gene expression in ear rot resistant and susceptible maize was confirmed by RNA microarray and qRT-PCR analyses. Further investigation suggests that the small heat shock protein family, some secondary metabolites, and the signaling pathways of abscisic acid (ABA, jasmonic acid (JA or salicylic acids (SA may be involved in the pathogen-associated molecular pattern-triggered immunity against F. verticillioides. These data will not only provide new insights into the molecular resistant mechanisms against fungi invading, but may also result in the identification of key molecular factors associated with ear rot resistance in maize.

  12. Characterization of resistance mechanisms and genetic relatedness of carbapenem-resistant Acinetobacter baumannii isolated from blood, Italy.

    Science.gov (United States)

    Migliavacca, Roberta; Espinal, Paula; Principe, Luigi; Drago, Monica; Fugazza, Giulia; Roca, Ignasi; Nucleo, Elisabetta; Bracco, Silvia; Vila, Jordi; Pagani, Laura; Luzzaro, Francesco

    2013-02-01

    The aim of this study was to characterize the resistance mechanisms and genetic relatedness of 21 carbapenem-resistant Acinetobacter baumannii blood isolates collected in Italy during a 1-year multicenter prospective surveillance study. Genes coding for carbapenemase production were identified by polymerase chain reaction (PCR) and sequencing. Pulsed-field gel electrophoresis (PFGE), multiplex PCRs for group identification, and multilocus sequence typing (MLST) were used to determine genetic relationships. Carbapenem resistance was consistently related to the production of oxacillinases, mostly the plasmid-mediated OXA-58 enzyme. Strains producing the OXA-23 enzyme (chromosomally mediated) were also detected. Seven PFGE clones were identified, some of which being related to international (ICL- I and ICL-II) or national clonal lineages. Multiplex PCRs identified 4 different groups (group 2 being dominant), further distinguishable in 6 sequence types by MLST. The heterogeneity of profiles highlights the diffusion of international and national clonal lineages in Italy. Continuous surveillance is needed for monitoring the spread of these worrisome strains equipped with multiple drug resistance mechanisms. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Non-genetic mechanisms communicating antibiotic resistance: rethinking strategies for antimicrobial drug design.

    Science.gov (United States)

    El-Halfawy, Omar M; Valvano, Miguel A

    2012-10-01

    Infections by multidrug-resistant bacteria are of great concern worldwide. In many cases, resistance is not due to the presence of specific antibiotic-modifying enzymes, but rather associated with a general impermeability of the bacterial cell envelope. The molecular bases of this intrinsic resistance are not completely understood. Moreover, horizontal gene transfers cannot solely explain the spread of intrinsic resistance among bacterial strains. This review focuses on the increased intrinsic antibiotic resistance mediated by small molecules. These small molecules can either be secreted from bacterial cells of the same or different species (e.g., indole, polyamines, ammonia, and the Pseudomonas quinolone signal) or be present in the bacterial cell milieu, whether in the environment, such as indole acetic acid and other plant hormones, or in human tissues and body fluids, such as polyamines. These molecules are metabolic byproducts that act as infochemicals and modulate bacterial responses toward antibiotics leading to increasing or decreasing resistance levels. The non-genetic mechanisms of antibiotic response modulation and communication discussed in this review should reorient our thinking of the mechanisms of intrinsic resistance to antibiotics and its spread across bacterial cell populations. The identification of chemical signals mediating increased intrinsic antibiotic resistance will expose novel critical targets for the development of new antimicrobial strategies.

  14. Drug Resistance in Malaria: Investigation of Mechanisms and Patterns of Drug Resistance and Cross Resistance in Malaria.

    Science.gov (United States)

    1987-10-19

    patients with G6PD deficiency . Furthermore, the increase in fer- riheme may mediate the selective toxicity of menadione for Plasmodium falciparum...may account for the resistance to malaria afforded by G6PD deficiency ." Next, we focused on the process of FP detoxification. Initially, we searched

  15. A molecular dynamics investigation on the crizotinib resistance mechanism of C1156Y mutation in ALK

    International Nuclear Information System (INIS)

    Sun, Hui-Yong; Ji, Feng-Qin

    2012-01-01

    Highlights: ► The study revealed the detailed resistance mechanism of the non-active mutation C1156Y in ALK. ► C1156Y leads to crizotinib displacement and conformational changes in the binding cavity. ► The conformations cause a decline in the vdW and electrostatic energy between crizotinib and ALK. -- Abstract: Crizotinib is an anaplastic lymphoma kinase (ALK) inhibitor that has recently been approved in the US for the treatment of non-small cell lung carcinoma (NSCLC). Despite its outstanding safety and efficacy, several resistant mutations against crizotinib have been detected in the treatment of NSCLC. However, in contrast to the widely accepted mechanism of steric hindrance by mutations at the active site, the mechanism by which the C1156Y non-active site mutation confers resistance against crizotinib remains unclear. In the present study, the resistance mechanism of C1156Y in ALK was investigated using molecular dynamics simulations. The results suggest that despite the non-active site mutation, C1156Y causes the dislocation of crizotinib as well as the indirect conformational changes in the binding cavity, which results in a marked decrease in the van der Waals and electrostatic interactions between crizotinib and ALK. The obtained results provide a detailed explanation of the resistance caused by C1156Y and may give a vital clue for the design of drugs to combat crizotinib resistance.

  16. Fluoroquinolone Resistance Mechanisms in an Escherichia coli Isolate, HUE1, Without Quinolone Resistance-Determining Region Mutations

    Directory of Open Access Journals (Sweden)

    Toyotaka eSato

    2013-05-01

    Full Text Available Fluoroquinolone resistance can cause major clinical problems. Here, we investigated fluoroquinolone resistance mechanisms in a clinical Escherichia coli isolate, HUE1, which had no mutations quinolone resistance-determining regions (QRDRs of DNA gyrase and topoisomerase IV. HUE1 demonstrated MICs that exceeded the breakpoints for ciprofloxacin, levofloxacin, and norfloxacin. HUE1 harbored oqxAB and qnrS1 on distinct plasmids. In addition, it exhibited lower intracellular ciprofloxacin concentrations and higher mRNA expression levels of efflux pumps and their global activators than did reference strains. The genes encoding AcrR (local AcrAB repressor and MarR (MarA repressor were disrupted by insertion of the transposon IS3-IS629 and a frameshift mutation, respectively. A series of mutants derived from HUE1 were obtained by plasmid curing and gene knockout using homologous recombination. Compared to the MICs of the parent strain HUE1, the fluoroquinolone MICs of these mutants indicated that qnrS1, oqxAB, acrAB, acrF, acrD, mdtK, mdfA, and tolC contributed to the reduced susceptibility to fluoroquinolone in HUE1. Therefore, fluoroquinolone resistance in HUE1 is caused by concomitant acquisition of QnrS1 and OqxAB and overexpression of AcrAB−TolC and other chromosome-encoded efflux pumps. Thus, we have demonstrated that QRDR mutations are not absolutely necessary for acquiring fluoroquinolone resistance in E. coli.

  17. Prevalence and Mechanism of Fluoroquinolone Resistance in Escherichia coli Isolated from Swine Feces in Korea.

    Science.gov (United States)

    Hu, Yoon Sung; Shin, Sook; Park, Yong Ho; Park, Kun Taek

    2017-07-01

    In this study, we investigated the prevalence and fluoroquinolone (FQ) resistance mechanisms in Escherichia coli isolated from swine fecal samples. E. coli isolates were collected from 171 (72.2%) of 237 swine fecal samples. Of these, 59 isolates (34.5%) were confirmed as FQ-resistant E. coli by the disk diffusion method. Of the FQ-resistant isolates, three major FQ resistance mechanisms were investigated. Of the 59 isolates, plasmid-mediated quinolone resistance genes were detected in 9 isolates (15.3%). Efflux pump activity was found in 56 isolates (94.9%); however, this was not correlated with the increased FQ resistance measured by determining the MIC. Point mutations in quinolone resistance-determining regions were the main cause of FQ resistance. All 59 ciprofloxacin-resistant isolates had mutations in quinolone resistance-determining regions; of these 59 isolates, all (100%) had mutations in gyrA, 58 (98.3%) had mutations in parC, 22 (37.3%) had mutations in parE, and none had mutations in gyrB. The predominant mutation type was double mutation in gyrA (Ser83Leu plus mutation in aspartic acid 87), and all FQ-resistant isolates (except one) that had mutations in parC or parE also had double mutations in gyrA. Importantly, the frequencies of multidrug-resistant and extended-spectrum β-lactamase-producing E. coli were significantly higher in the high ciprofloxacin MIC group in this study. Compared with previous studies in Korea, the prevalence of FQ resistance and plasmid-mediated quinolone resistance genes had increased considerably in swine. Although the use of FQ as a feed additive is prohibited in Korea, use for self-treatment and therapeutic purposes has been increasing, which may be responsible for the higher FQ resistance rate observed in this study. Therefore, prudent use of FQ on animal farms is warranted to reduce the evolution of FQ-resistant bacteria in the animal industry.

  18. Corrosion resistant iron aluminides exhibiting improved mechanical properties and corrosion resistance

    Science.gov (United States)

    Liu, Chain T.; McKamey, Claudette G.; Tortorelli, Peter F.; David, Stan A.

    1994-01-01

    The specification discloses a corrosion-resistant intermetallic alloy comprising, in atomic percent, an FeAl iron aluminide containing from about 30 to about 40% aluminum alloyed with from about 0.01 to 0.4% zirconium and from 0.01 to about 0.8% boron. The alloy exhibits considerably improved room temperature ductility for enhanced usefulness in structural applications. The high temperature strength and fabricability is improved by alloying with molybdenum, carbon, chromium and vanadium.

  19. Friction in Sliding Orthodontic Mechanics: Ceramic Brackets, Teflon-Coated Wires and Comparative Resistances

    Science.gov (United States)

    1989-01-01

    N Tn FRICTION IN SLIDING ORTHODONTIC MECHANICS: N CERAMIC BRACKETS, TEFLON-COATED WIRES , AND COMPARATIVE RESISTANCES 0 DTICSFLECTED James R. Gill1...obsolete. SECURITY CLASSIFICATION OF THIS PAGE AFIT/CI "OVERPRINT" I FRICTION IN SLIDING ORTHODONTIC MECHANICS: CERAMIC BRACKETS, TEFLON-COATED WIRES ...brackets, arch- wires , and ligations during simulated orthodontic edgewise sliding mechanics. Independent variables and their values were 1) bracket

  20. Development of a resilient mechanical sealing solution to resist electro corrosion in ultrapure feedwater applications

    Energy Technology Data Exchange (ETDEWEB)

    Loenhout, Gerard van [Flowservice Flow Solutions Division, Etten-Leur (Netherlands); Enders, Klaus; Schmerberg, Rainer [Vattenfall Europe Generation AG, Peitz (Germany)

    2012-11-01

    Ever since the introduction of mechanical seals on high speed boiler feed pumps in the sixties, mechanical seals have proven to be a reliable, cost effective sealing method. However, since the introduction of combined water treatment chemistry used in today's modern fossil-fuelled power stations, keeping mechanical seal reliability high, became a challenge. A pragmatic approach is presented. A resilient sealing solution was developed to resist electro corrosion for such critical feed water pumps. (orig.)

  1. Mechanism of single-layer 193-nm dissolution inhibition resist

    Science.gov (United States)

    Yan, Zhenglin; Houlihan, Francis M.; Reichmanis, Elsa; Nalamasu, Omkaram; Reiser, Arnost; Dabbagh, Gary; Hutton, Richard S.; Osei, Dan; Sousa, Jose; Bolan, Kevin J.

    2000-06-01

    We have found that the progress of developer base into films of terpolymers of norbornene (NB)-maleic anhydride (MA) and acrylic acid (AA) is a percolation process with a critical site concentration of x(c) equals 0.084 which suggests that every acrylic acid site in the terpolymer of norbornene-maleic anhydride-acrylic acid can make 12 monomer units of the polymer water compatible. In practice these systems are being used with various tert-butyl esters of cholic acid as dissolution inhibitors. The cholates differ very much in their dissolution inhibition factors (lowest t-butyl cholate (1.3) to highest t-butyl lithocholate glutarate dimer (7.4). The change in these factors corrected for molarity follow the hydrophobic character of the dissolution as measured by log(p). A quick screening method has also been established to evaluate dissolution inhibitors based on our observation that the cloud point (the volume % acetone in a water/acetone which gives persistent cloudiness) parallels the dissolution inhibiting power as measured by the dissolution inhibition factor. For dissolution promotion, optimal results are obtained with t-butyl 1,3,5-cyclohexanetricarboxylate (f equals -6.3) and poorest results with t-butyl lithocholate (f equals -2.8); this appears to track with the number of carboxyl groups and the hydrophobicity of the carboxylic acids. The Rmax found for resist formulations tracks well with these findings. Another factor in determining the ultimate achievable contrast is the degree of acidolytic deprotection achieved by the material. It appears that acidolyticaly cleaveable carboxylate esters with a higher concentration of electron withdrawing groups such as t-butyl 1,3,5-cyclohexanetricarboxylate are more effective.

  2. Molecular epidemiology and drug resistant mechanism in carbapenem-resistant Klebsiella pneumoniae isolated from pediatric patients in Shanghai, China.

    Science.gov (United States)

    Zhang, Xingyu; Chen, Di; Xu, Guifeng; Huang, Weichun; Wang, Xing

    2018-01-01

    Infection by carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a public health challenge worldwide, in particular among children, which was associated with high morbidity and mortality rates. There was limited data in pediatric populations, thus this study aimed to investigate molecular epidemiology and drug resistant mechanism of CR-KP strains from pediatric patients in Shanghai, China. A total of 41 clinical CR-KP isolates from sputum, urine, blood or drainage fluid were collected between July 2014 and May 2015 in Shanghai Children's Medical Center. Multilocus sequence typing (MLST), antibiotic susceptibility testing, PCR amplification and sequencing of the drug resistance associated genes were applied to all these isolates. MLST analysis revealed 16 distinct STs identified within the 41 isolates, among which the most frequently represented were ST11(19.5%),ST25(14.6%),ST76(14.6%),ST37(9.8%).One new ST was first identified. All CR-KP isolates showed MDR phenotypes and were resistance to ceftazidime, imipenem, piperacillin / tazobactam, ceftriaxone, ampicillin /sulbactam, aztreonam. They were confirmed as carbapenemase producer, NDM-1 (56.1%, 23/41), IMP (26.8%, 11/41), KPC-2 (22.0%, 9/41) were detected. Of note, two isolates carried simultaneously both NDM-1 and IMP-4. All CR-KP strains contained at least one of extended spectrum β-lactamase genes tested(TEM, SHV, OXA-1, CTX-M group) and six isolates carried both ESBL and AmpC genes(DHA-1). Among the penicllinase and β-lactamase genes, the most frequently one is SHV(92.7%,38/41), followed by TEM-1(68.3%,28/41), CTX-M-14(43.9%,18/41), CTX-M-15(43.9%,14/41), OXA-1(14.6%,6/41). In the present study, NDM-1-producing isolates was the predominant CR-KP strains in children, follow by IMP and KPC-producing strains. NDM-1and IMP-4 were more frequent than KPC-2 and showed a multiclonal background. Those suggested carbapenem-resistant in children is diverse, and certain resistance mechanisms differ from prevalent

  3. Resistive switching properties and physical mechanism of europium oxide thin films

    Energy Technology Data Exchange (ETDEWEB)

    Xie, Wei; Zou, Changwei [School of Physical Science and Technology, Lingnan Normal University, Zhanjiang (China); Bao, Dinghua [State Key Laboratory of Optoelectronic Materials and Technologies, School of Materials Science and Engineering, Sun Yat-Sen University, Guangzhou (China)

    2017-09-15

    A forming-free resistive switching effect was obtained in Pt/Eu{sub 2}O{sub 3}/Pt devices in which the Eu{sub 2}O{sub 3} thin films were fabricated by a chemical solution deposition method. The devices show unipolar resistive switching with excellent switching parameters, such as high resistance ratio (10{sup 7}), stable resistance values (read at 0.2 V), low reset voltage, good endurance, and long retention time (up to 10{sup 4} s). On the basis of the analysis of the current-voltage (I-V) curves and the resistance-temperature dependence, it can be concluded that the dominant conducting mechanisms were ohmic behavior and Schottky emission at low resistance state and high resistance state, respectively. The resistive switching behavior could be explained by the formation and rupture of conductive filament, which is related to the abundant oxygen vacancies generated in the deposition process. This work demonstrates the great potential opportunities of Eu{sub 2}O{sub 3} thin film in resistive switching memory applications, which might possess distinguished properties. (copyright 2017 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  4. Investigation of corrosion resistance of alloys with high mechanical characteristics in some environments of food industry

    International Nuclear Information System (INIS)

    Tremoureux, Yves

    1978-01-01

    This research thesis aimed at improving knowledge in the field of stress-free corrosion of alloys with high mechanical characteristics in aqueous environments, at highlighting some necessary aspects of their behaviour during cleaning or disinfection, and at selecting alloys which possess a good stress-free corrosion resistance in view of a later investigation of their stress corrosion resistance. After a presentation of the metallurgical characteristics of high mechanical strength alloys and the report of a bibliographical study on corrosion resistance of these alloys, the author presents and discusses the results obtained in the study of a possible migration of metallic ions in a milk product which is submitted to a centrifugation, and of the corrosion resistance of selected alloys with respect to the different media they will be in contact with during ultra-centrifugation. The following alloys have been used in this research: Marval 18, Marphynox, Marval X12, 17-4PH steel, Inconel 718 [fr

  5. 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

  6. Mechanism by which arylamine N-acetyltransferase 1 ablation causes insulin resistance in mice

    DEFF Research Database (Denmark)

    Camporez, João Paulo; Wang, Yongliang; Faarkrog, Kasper

    2017-01-01

    A single-nucleotide polymorphism in the human arylamine N-acetyltransferase 2 (Nat2) gene has recently been identified as associated with insulin resistance in humans. To understand the cellular and molecular mechanisms by which alterations in Nat2 activity might cause insulin resistance, we...... examined murine ortholog Nat1 knockout (KO) mice. Nat1 KO mice manifested whole-body insulin resistance, which could be attributed to reduced muscle, liver, and adipose tissue insulin sensitivity. Hepatic and muscle insulin resistance were associated with marked increases in both liver and muscle...... adipose tissue, and hepatocytes. Taken together, these studies demonstrate that Nat1 deletion promotes reduced mitochondrial activity and is associated with ectopic lipid-induced insulin resistance. These results provide a potential genetic link among mitochondrial dysfunction with increased ectopic lipid...

  7. Insulin Signaling, Resistance, and the Metabolic Syndrome: Insights from Mouse Models to Disease Mechanisms

    OpenAIRE

    Guo, Shaodong

    2014-01-01

    Insulin resistance is a major underlying mechanism for the “metabolic syndrome”, which is also known as insulin resistance syndrome. Metabolic syndrome is increasing at an alarming rate, becoming a major public and clinical problem worldwide. Metabolic syndrome is represented by a group of interrelated disorders, including obesity, hyperglycemia, hyperlipidemia, and hypertension. It is also a significant risk factor for cardiovascular disease and increased morbidity and mortality. Animal stud...

  8. Bulgecin A as a β-lactam enhancer for carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii clinical isolates containing various resistance mechanisms

    Directory of Open Access Journals (Sweden)

    Skalweit MJ

    2016-09-01

    Full Text Available Marion J Skalweit,1–5 Mei Li2 1Department of Medicine, 2Research Section, 3Infectious Diseases Section, Louis Stokes Cleveland Department of Veterans, 4Department of Medicine, 5Department of Biochemistry, Case Western Reserve University School of Medicine, Cleveland, OH, USA Abstract: Genetic screening of Pseudomonas aeruginosa (PSDA and Acinetobacter ­baumannii (ACB reveals genes that confer increased susceptibility to β-lactams when disrupted, suggesting novel drug targets. One such target is lytic transglycosylase. Bulgecin A (BlgA is a natural product of Pseudomonas mesoacidophila and a lytic transglycosolase inhibitor that works synergistically with β-lactams targeting PBP3 for Enterobacteriaceae. BlgA also weakly inhibits di-Zn2+ metallo-β-lactamases like L1 of Stenotrophomonas maltophilia. We hypothesized that because of its unique mechanism of action, BlgA could restore susceptibility to carbapenems in carbapenem-resistant PSDA (CR-PSDA and carbapenem-resistant ACB, as well as ACB resistant to sulbactam. A BlgA-containing extract was prepared using a previously published protocol. CR-PSDA clinical isolates demonstrating a variety of carbapenem resistance mechanisms (VIM-2 carbapenemases, efflux mechanisms, and AmpC producer expression were characterized with agar dilution minimum inhibitory concentration (MIC testing and polymerase chain reaction. Growth curves using these strains were prepared using meropenem, BlgA extract, and meropenem plus BlgA extract. A concentrated Blg A extract combined with low concentrations of meropenem, was able to inhibit the growth of clinical strains of CR-PSDA for strains that had meropenem MICs ≥8 mg/L by agar dilution, and a clinical strain of an OXA-24 producing ACB that had a meropenem MIC >32 mg/L and intermediate ampicillin/sulbactam susceptibility. Similar experiments were conducted on a TEM-1 producing ACB strain resistant to sulbactam. BlgA with ampicillin/sulbactam inhibited the growth

  9. Molecular mechanisms associated with nosocomial carbapenem-resistant Acinetobacter baumannii in Mexico.

    Science.gov (United States)

    Alcántar-Curiel, María Dolores; García-Torres, Luis Francisco; González-Chávez, María Inés; Morfín-Otero, Rayo; Gayosso-Vázquez, Catalina; Jarillo-Quijada, Ma Dolores; Fernández-Vázquez, José Luis; Giono-Cerezo, Silvia; Rodríguez-Noriega, Eduardo; Santos-Preciado, José Ignacio

    2014-10-01

    Acinetobacter baumannii is an emerging pathogen worldwide that is most commonly associated with nosocomial infections and multi-drug resistance. In the present study we determined the mechanisms of carbapenem resistance and clonal diversity of A. baumannii nosocomial isolates in Hospital Civil de Guadalajara, Mexico. A total of 303 clinical isolates of A. baumannii identified during a period expanding from 2004-2011 were analyzed for carbapenem resistance using several microbiological and molecular methods. Clonal relatedness of these isolates was determined using pulsed-field gel electrophoresis. Of the 303 isolates, 84% were resistant to meropenem, 71.3% to imipenem and 78.3% the resistant isolates were positive for metallo-β-lactamases as determined by the phenotypic assay. In addition, 49.6% of carbapenem-intermediate or -resistant isolates carried the blaOXA-72 gene and 1.2% carried the blaVIM-1 gene. Efflux pump phenotype was responsible for reduced susceptibility to meropenem in 14.5% and to imipenem in 31.6% of the resistant isolates, respectively in the presence of the efflux pump inhibitor, carbonyl cyanide 3-chlorophenylhydrazone. Strains representing different carbapenem-resistant patterns exhibited reduced expression of 22, 29, 33, and 43 kDa OMPs. Among the bacterial collection studied, 48 different clones were identified, two of which were predominant and persistently transmitted. Carbapenemase production in combination with efflux pump expression, reduction in OMPs expression and the cross-transmission of clones appear to be major contributors to the high frequency of carbapenem-resistance observed in A. baumannii. To our knowledge, this is the first study to define the molecular mechanisms associated with carbapenem-resistance in A. baumannii in Mexico. Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

  10. Use of mutagenesis, genetic mapping and next generation transcriptomics to investigate insecticide resistance mechanisms.

    Directory of Open Access Journals (Sweden)

    Predrag Kalajdzic

    Full Text Available Insecticide resistance is a worldwide problem with major impact on agriculture and human health. Understanding the underlying molecular mechanisms is crucial for the management of the phenomenon; however, this information often comes late with respect to the implementation of efficient counter-measures, particularly in the case of metabolism-based resistance mechanisms. We employed a genome-wide insertional mutagenesis screen to Drosophila melanogaster, using a Minos-based construct, and retrieved a line (MiT[w(-]3R2 resistant to the neonicotinoid insecticide Imidacloprid. Biochemical and bioassay data indicated that resistance was due to increased P450 detoxification. Deep sequencing transcriptomic analysis revealed substantial over- and under-representation of 357 transcripts in the resistant line, including statistically significant changes in mixed function oxidases, peptidases and cuticular proteins. Three P450 genes (Cyp4p2, Cyp6a2 and Cyp6g1 located on the 2R chromosome, are highly up-regulated in mutant flies compared to susceptible Drosophila. One of them (Cyp6g1 has been already described as a major factor for Imidacloprid resistance, which validated the approach. Elevated expression of the Cyp4p2 was not previously documented in Drosophila lines resistant to neonicotinoids. In silico analysis using the Drosophila reference genome failed to detect transcription binding factors or microRNAs associated with the over-expressed Cyp genes. The resistant line did not contain a Minos insertion in its chromosomes, suggesting a hit-and-run event, i.e. an insertion of the transposable element, followed by an excision which caused the mutation. Genetic mapping placed the resistance locus to the right arm of the second chromosome, within a ∼1 Mb region, where the highly up-regulated Cyp6g1 gene is located. The nature of the unknown mutation that causes resistance is discussed on the basis of these results.

  11. Antimicrobial resistance (AMR) nanomachines-mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation.

    Science.gov (United States)

    Phillips-Jones, Mary K; Harding, Stephen E

    2018-04-01

    In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics-the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that

  12. Overcoming ABC transporter-mediated multidrug resistance: Molecular mechanisms and novel therapeutic drug strategies.

    Science.gov (United States)

    Li, Wen; Zhang, Han; Assaraf, Yehuda G; Zhao, Kun; Xu, Xiaojun; Xie, Jinbing; Yang, Dong-Hua; Chen, Zhe-Sheng

    2016-07-01

    Multidrug resistance is a key determinant of cancer chemotherapy failure. One of the major causes of multidrug resistance is the enhanced efflux of drugs by membrane ABC transporters. Targeting ABC transporters projects a promising approach to eliminating or suppressing drug resistance in cancer treatment. To reveal the functional mechanisms of ABC transporters in drug resistance, extensive studies have been conducted from identifying drug binding sites to elucidating structural dynamics. In this review article, we examined the recent crystal structures of ABC proteins to depict the functionally important structural elements, such as domains, conserved motifs, and critical amino acids that are involved in ATP-binding and drug efflux. We inspected the drug-binding sites on ABC proteins and the molecular mechanisms of various substrate interactions with the drug binding pocket. While our continuous battle against drug resistance is far from over, new approaches and technologies have emerged to push forward our frontier. Most recent developments in anti-MDR strategies include P-gp inhibitors, RNA-interference, nano-medicines, and delivering combination strategies. With the advent of the 'Omics' era - genomics, epigenomics, transcriptomics, proteomics, and metabolomics - these disciplines play an important role in fighting the battle against chemoresistance by further unraveling the molecular mechanisms of drug resistance and shed light on medical therapies that specifically target MDR. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Pseudomonas aeruginosa May Accumulate Drug Resistance Mechanisms without Losing Its Ability To Cause Bloodstream Infections▿

    Science.gov (United States)

    Hocquet, Didier; Berthelot, Philippe; Roussel-Delvallez, Micheline; Favre, Roger; Jeannot, Katy; Bajolet, Odile; Marty, Nicole; Grattard, Florence; Mariani-Kurkdjian, Patricia; Bingen, Edouard; Husson, Marie-Odile; Couetdic, Gérard; Plésiat, Patrick

    2007-01-01

    In this study, we systematically investigated the resistance mechanisms to β-lactams, aminoglycosides, and fluoroquinolones of 120 bacteremic strains of Pseudomonas aeruginosa. Pulsed-field gel electrophoresis genotyping showed that 97 of these strains were represented by a single isolate, 10 by 2 and 1 by 3 clonally related isolates, respectively. Seventy-five percent (90 out of 120) of the bacteremic P. aeruginosa strains displayed a significant resistance to one or more of the tested antimicrobials (up to 11 for 1 strain). These strains were found to harbor a great diversity of resistance mechanisms (up to 7 in 1 strain), leading to various levels of drug resistance. Interestingly, 11 and 36% of the isolates appeared to overproduce the MexAB-OprM and MexXY-OprM efflux systems, respectively. Altogether, our results show that P. aeruginosa may accumulate intrinsic (overproduction of cephalosporinase AmpC, increased drug efflux, fluoroquinolone target mutations, and deficient production of porin OprD) and exogenous (production of secondary β-lactamases and aminoglycoside-modifying enzymes) resistance mechanisms without losing its ability to generate severe bloodstream infections. Consequently, clinicians should be aware that multidrug-resistant P. aeruginosa may remain fully pathogenic. PMID:17682106

  14. Survey on the phage resistance mechanisms displayed by a dairy Lactobacillus helveticus strain.

    Science.gov (United States)

    Zago, Miriam; Orrù, Luigi; Rossetti, Lia; Lamontanara, Antonella; Fornasari, Maria Emanuela; Bonvini, Barbara; Meucci, Aurora; Carminati, Domenico; Cattivelli, Luigi; Giraffa, Giorgio

    2017-09-01

    In this study the presence and functionality of phage defence mechanisms in Lactobacillus helveticus ATCC 10386, a strain of dairy origin which is sensitive to ΦLh56, were investigated. After exposure of ATCC 10386 to ΦLh56, the whole-genome sequences of ATCC 10386 and of a phage-resistant derivative (LhM3) were compared. LhM3 showed deletions in the S-layer protein and a higher expression of the genes involved in the restriction/modification (R/M) system. Genetic data were substantiated by measurements of bacteriophage adsorption rates, efficiency of plaquing, cell wall protein size and by gene expression analysis. In LhM3 two phage resistance mechanisms, the inhibition of phage adsorption and the upregulation of Type I R/M genes, take place and explain its resistance to ΦLh56. Although present in both ATCC 10386 and LhM3 genomes, the CRISPR machinery did not seem to play a role in the phage resistance of LhM3. Overall, the natural selection of phage resistant strains resulted successful in detecting variants carrying multiple phage defence mechanisms in L. helveticus. The concurrent presence of multiple phage-resistance systems should provide starter strains with increased fitness and robustness in dairy ecosystems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Insulin Resistance and Cancer Risk: An Overview of the Pathogenetic Mechanisms

    Directory of Open Access Journals (Sweden)

    Biagio Arcidiacono

    2012-01-01

    Full Text Available Insulin resistance is common in individuals with obesity or type 2 diabetes (T2D, in which circulating insulin levels are frequently increased. Recent epidemiological and clinical evidence points to a link between insulin resistance and cancer. The mechanisms for this association are unknown, but hyperinsulinaemia (a hallmark of insulin resistance and the increase in bioavailable insulin-like growth factor I (IGF-I appear to have a role in tumor initiation and progression in insulin-resistant patients. Insulin and IGF-I inhibit the hepatic synthesis of sex-hormone binding globulin (SHBG, whereas both hormones stimulate the ovarian synthesis of sex steroids, whose effects, in breast epithelium and endometrium, can promote cellular proliferation and inhibit apoptosis. Furthermore, an increased risk of cancer among insulin-resistant patients can be due to overproduction of reactive oxygen species (ROS that can damage DNA contributing to mutagenesis and carcinogenesis. On the other hand, it is possible that the abundance of inflammatory cells in adipose tissue of obese and diabetic patients may promote systemic inflammation which can result in a protumorigenic environment. Here, we summarize recent progress on insulin resistance and cancer, focusing on various implicated mechanisms that have been described recently, and discuss how these mechanisms may contribute to cancer initiation and progression.

  16. Mechanisms of pyrethroid resistance inHaematobia irritans (Muscidae from Mato Grosso do Sul state, Brazil

    Directory of Open Access Journals (Sweden)

    Antonio Thadeu Medeiros Barros

    Full Text Available Horn fly resistance to pyrethroid insecticides occurs throughout Brazil, but knowledge about the involved mechanisms is still in an incipient stage. This survey was aimed to identify the mechanisms of horn fly resistance to cypermethrin in Mato Grosso do Sul state, Brazil. Impregnated filter paper bioassays using cypermethrin, synergized or not with piperonyl butoxide (PBO and triphenyl phosphate (TPP, were conducted from March 2004 to June 2005 in horn fly populations (n = 33 from all over the state. All populations were highly resistant to cypermethrin, with resistance factors (RF ranging from 89.4 to 1,020.6. Polymerase chain reaction (PCR assays to detect the knockdown resistance (kdr mutation also were performed in 16 samples. The kdr mutation was found in 75% of the tested populations, mostly with relatively low frequencies (<20%, and was absent in some highly resistant populations. Addition of TPP did not significantly reduce the LC50 in any population. However, PBO reduced LC50s above 40-fold in all tested populations, resulting in RFs ≤ 10 in most cases. Horn fly resistance to cypermethrin is widespread in the state, being primarily caused by an enhanced activity of P450 mono-oxygenases and secondarily by reduced target site sensitivity.

  17. Conducting mechanism of Ag-diffused Bi-Te based resistive switching devices

    Science.gov (United States)

    Liu, N.; Yan, P.; Li, Y.; Lu, K.; Sun, H. J.; Ji, H. K.; Xue, K. H.; Miao, X. S.

    2018-02-01

    The forming-free resistive switching (RS) and conducting mechanism of Ag-diffused BiTe chalcogenide thin film has been investigated. The mutual diffusion of Ag, Bi and Te elements at the interface is proved to suppress the crystallization of the as-deposited BiTe film. The amorphization of BiTe and the Schottky barrier between Ag and BiTe contribute to high resistance state (HRS) of the switching devices. When switched to low resistance state (LRS), the coexistence of metallic conduction and variable-range hopping is found to be the dominant conduction mechanism. The temperature dependence of LRS exhibits an interesting transport behavior, so that a positive temperature coefficient becomes a negative one at 24 K. Our results help to further understand the conduction mechanism and promote the design for future nonvolatile memory applications.

  18. [Isolation of a carbapenem-resistant K1 serotype Klebsiella pneumonia strain and the study of resistance mechanism].

    Science.gov (United States)

    Zhang, Rong; Wang, Xuan; Lü, Jianxin

    2014-12-16

    To study the virulence and mechanism of carbapenem resistance of a clinical isolate of carbapenem-resistant K1 serotype Klebsiella pneumonia strain. Identification of isolate was carried out with VITEK-2 compact system. Antimicrobial susceptibility was determined by E-test; Metallo β-lactamases and carbapenemases screening were conducted by imipenem-EDTA double disc synergy test and modified Hodge test, respectively.Specific polymerehse chain reaction (PCR) and DNA sequencing were preformed to detect the virulence genes including K1, K2, K5, K20, K54, K57, magA, rmpA, wcaG and a series of β-lactamase resistence genes. Conjunction experiment was also performed. The plasmids of transconjugants were submitted to PCR-based replicon typing (PBRT) method. Molecular typing was performed by multilocus sequence typing (MLST). Antimicrobial susceptibility testing revealed that the Klebsiella pneumonia strain was resistant to most of the antibiotics used in clinic. Phynotype confirmary rest revealed the production of carbapanemases, while Metallo β-lactamases were negative; PCR and DNA sequencing confirmed the isolate was positive for blaKPC-2, blaCTX-M-15, blaTEM-1, blaSHV-1 and virulence genes K1, magA, rmpA, wcaG simultaneously; blaKPC-2 was transferred from donor to Escherichia EC600 by conjunction experiment, while no virulence genes were found in the transconjugants. PBRT revealed that Frep plasmid was found in transconjugants. MLST analysis revealed that this strain belonged to ST23. K1 serotype Klebsiella pneumonia strain carries virulence genes and carbapenem resistance gene blaKPC-2, noteworthily the carbapenem resistance genes can be transferred through horizontal transmission on plasmids.

  19. Mechanisms of group A Streptococcus resistance to reactive oxygen species

    Science.gov (United States)

    Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N.

    2015-01-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the ‘top 10’ causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•−), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. PMID:25670736

  20. Mechanisms of group A Streptococcus resistance to reactive oxygen species.

    Science.gov (United States)

    Henningham, Anna; Döhrmann, Simon; Nizet, Victor; Cole, Jason N

    2015-07-01

    Streptococcus pyogenes, also known as group A Streptococcus (GAS), is an exclusively human Gram-positive bacterial pathogen ranked among the 'top 10' causes of infection-related deaths worldwide. GAS commonly causes benign and self-limiting epithelial infections (pharyngitis and impetigo), and less frequent severe invasive diseases (bacteremia, toxic shock syndrome and necrotizing fasciitis). Annually, GAS causes 700 million infections, including 1.8 million invasive infections with a mortality rate of 25%. In order to establish an infection, GAS must counteract the oxidative stress conditions generated by the release of reactive oxygen species (ROS) at the infection site by host immune cells such as neutrophils and monocytes. ROS are the highly reactive and toxic byproducts of oxygen metabolism, including hydrogen peroxide (H2O2), superoxide anion (O2•(-)), hydroxyl radicals (OH•) and singlet oxygen (O2*), which can damage bacterial nucleic acids, proteins and cell membranes. This review summarizes the enzymatic and regulatory mechanisms utilized by GAS to thwart ROS and survive under conditions of oxidative stress. © FEMS 2015.

  1. Global analysis of the evolution and mechanism of echinocandin resistance in Candida glabrata.

    Directory of Open Access Journals (Sweden)

    Sheena D Singh-Babak

    Full Text Available The evolution of drug resistance has a profound impact on human health. Candida glabrata is a leading human fungal pathogen that can rapidly evolve resistance to echinocandins, which target cell wall biosynthesis and are front-line therapeutics for Candida infections. Here, we provide the first global analysis of mutations accompanying the evolution of fungal drug resistance in a human host utilizing a series of C. glabrata isolates that evolved echinocandin resistance in a patient treated with the echinocandin caspofungin for recurring bloodstream candidemia. Whole genome sequencing identified a mutation in the drug target, FKS2, accompanying a major resistance increase, and 8 additional non-synonymous mutations. The FKS2-T1987C mutation was sufficient for echinocandin resistance, and associated with a fitness cost that was mitigated with further evolution, observed in vitro and in a murine model of systemic candidemia. A CDC6-A511G(K171E mutation acquired before FKS2-T1987C(S663P, conferred a small resistance increase. Elevated dosage of CDC55, which acquired a C463T(P155S mutation after FKS2-T1987C(S663P, ameliorated fitness. To discover strategies to abrogate echinocandin resistance, we focused on the molecular chaperone Hsp90 and downstream effector calcineurin. Genetic or pharmacological compromise of Hsp90 or calcineurin function reduced basal tolerance and resistance. Hsp90 and calcineurin were required for caspofungin-dependent FKS2 induction, providing a mechanism governing echinocandin resistance. A mitochondrial respiration-defective petite mutant in the series revealed that the petite phenotype does not confer echinocandin resistance, but renders strains refractory to synergy between echinocandins and Hsp90 or calcineurin inhibitors. The kidneys of mice infected with the petite mutant were sterile, while those infected with the HSP90-repressible strain had reduced fungal burden. We provide the first global view of mutations

  2. Mechanism of sulfonylurea herbicide resistance in the broadleaf weed, Kochia scoparia

    International Nuclear Information System (INIS)

    Saari, L.L.; Cotterman, J.C.; Primiani, M.M.

    1990-01-01

    Selection of kochia (Kochia scoparia) biotypes resistant to the sulfonylurea herbicide chlorsulfuron has occurred through the continued use of this herbicide in monoculture cereal-growing areas in the United States. The apparent sulfonylurea resistance observed in kochia was confirmed in greenhouse tests. Fresh and dry weight accumulation in the resistance kochia was 2- to >350-fold higher in the presence of four sulfonylurea herbicides as compared to the susceptible biotype. Acetolactate synthase (ALS) activity isolated from sulfonylurea-resistant kochia was less sensitive to inhibition by three classes of ALS-inhibiting herbicides, sulfonylureas, imidazolinones, and sulfonanilides. The decrease in ALS sensitivity to inhibition (as measured by the ratio of resistant I 50 to susceptible I 50 ) was 5- to 28-fold, 2- to 6-fold, and 20-fold for sulfonylurea herbicides, imidazolinone herbicides, and a sulfonanilide herbicide, respectively. No differences were observed in the ALS-specific activities or the rates of [ 14 C]chlorsulfuron uptake, translocation, and metabolism between susceptible and resistant kochia biotypes. The K m values for pyruvate using ALS from susceptible and resistant kochia were 2.13 and 1.74 mM, respectively. Based on these results, the mechanism of sulfonylurea resistance in this kochia biotype is due solely to a less sulfonylurea-sensitive ALS enzyme

  3. Mechanisms of Bactericide Resistance in Phytopathogenic Bacteria(Abstracts of the Research by the Winners of the Young Scientist Award)

    OpenAIRE

    Masami, NAKAJIMA; School of Agriculture, Ibaraki University

    2002-01-01

    Bactericides containing copper and streptomycin have been widely used to control bacterial plant diseases. However, the efficacy of copper and streptomycin have been reduced by the development of copper- and streptomycin-resistant bacterial strains. Understanding the mechanism of resistance is necessary for the prevention and management of resistance. In this study, the mechanisms of copper and streptomycin resistance in Pseudomonas syringae pv. actinidiae were analyzed.

  4. A cfr-positive clinical staphylococcal isolate from India with multiple mechanisms of linezolid-resistance

    Directory of Open Access Journals (Sweden)

    Vineeth Rajan

    2014-01-01

    Full Text Available Background & objectives: Linezolid, a member of the oxazolidinone class of antibiotics, has been an effective therapeutic option to treat severe infections caused by multidrug resistant Gram positive bacteria. Emergence of linezolid resistant clinical strains is a serious issue in the healthcare settings worldwide. We report here the molecular characterization of a linezolid resistant clinical isolate of Staphylococcus haemolyticus from India. Methods: The species of the clinical isolate was identified by 16S rRNA gene sequencing. The minimum inhibitory concentrations (MICs of linezolid, clindamycin, chloramphenicol and oxacillin were determined by E-test method. To elucidate the mechanism of linezolid-resistance, presence of cfr gene (chloramphenicol florfenicol resistance and mutations in 23S rRNA and ribosomal proteins (L3, L4 and L22 were investigated. Staphylococcal Cassette Chromosome mec (SCCmec typing was performed by multiplex PCR. Results: The study documented a rare clinical S. haemolyticus strain with three independent mechanisms of linezolid-resistance. The strain carried cfr gene, the only known transmissible mechanism of linezolid-resistance. The strain also possessed resistance-conferring mutations such as G 2576 T in domain V of 23S rRNA gene and Met 156 Thr in L3 ribosomal protein. The other ribosomal proteins (L4 and L22 did not exhibit mutations accountable for linezolid-resistance. Restriction digestion by NheI revealed that all the alleles of 23S rRNA gene were mutated. The isolate showed elevated MIC values (>256 ΅g ml -[1] of linezolid, clindamycin, chloramphenicol and oxacillin. Methicillin resistance was conferred by type I SCCmec element. The strain also harboured lsa(B gene which encodes an ABC transporter that can efflux clindamycin. Interpretation & conclusions: The present study reports the first clinical strain from India with transmissible and multiple mechanisms of linezolid-resistance. Judicious use of

  5. Distinguishing Antimicrobial Models with Different Resistance Mechanisms via Population Pharmacodynamic Modeling.

    Directory of Open Access Journals (Sweden)

    Matthieu Jacobs

    2016-03-01

    Full Text Available Semi-mechanistic pharmacokinetic-pharmacodynamic (PK-PD modeling is increasingly used for antimicrobial drug development and optimization of dosage regimens, but systematic simulation-estimation studies to distinguish between competing PD models are lacking. This study compared the ability of static and dynamic in vitro infection models to distinguish between models with different resistance mechanisms and support accurate and precise parameter estimation. Monte Carlo simulations (MCS were performed for models with one susceptible bacterial population without (M1 or with a resting stage (M2, a one population model with adaptive resistance (M5, models with pre-existing susceptible and resistant populations without (M3 or with (M4 inter-conversion, and a model with two pre-existing populations with adaptive resistance (M6. For each model, 200 datasets of the total bacterial population were simulated over 24h using static antibiotic concentrations (256-fold concentration range or over 48h under dynamic conditions (dosing every 12h; elimination half-life: 1h. Twelve-hundred random datasets (each containing 20 curves for static or four curves for dynamic conditions were generated by bootstrapping. Each dataset was estimated by all six models via population PD modeling to compare bias and precision. For M1 and M3, most parameter estimates were unbiased (<10% and had good imprecision (<30%. However, parameters for adaptive resistance and inter-conversion for M2, M4, M5 and M6 had poor bias and large imprecision under static and dynamic conditions. For datasets that only contained viable counts of the total population, common statistical criteria and diagnostic plots did not support sound identification of the true resistance mechanism. Therefore, it seems advisable to quantify resistant bacteria and characterize their MICs and resistance mechanisms to support extended simulations and translate from in vitro experiments to animal infection models and

  6. Prestressing Shock Resistant Mechanical Components and Mechanisms Made from Hard, Superelastic Materials

    Science.gov (United States)

    DellaCorte, Christopher (Inventor)

    2014-01-01

    A method and an apparatus confer full superelastic properties to the active surface of a mechanical component constructed of a superelastic material prior to service. A compressive load is applied to the active surface of the mechanical component followed by removing the compressive load from the active surface whereby substantially all load strain is recoverable after applying and removing of subsequent compressive loads.

  7. Bulgecin A as a β-lactam enhancer for carbapenem-resistant Pseudomonas aeruginosa and carbapenem-resistant Acinetobacter baumannii clinical isolates containing various resistance mechanisms.

    Science.gov (United States)

    Skalweit, Marion J; Li, Mei

    2016-01-01

    Genetic screening of Pseudomonas aeruginosa (PSDA) and Acinetobacter baumannii (ACB) reveals genes that confer increased susceptibility to β-lactams when disrupted, suggesting novel drug targets. One such target is lytic transglycosylase. Bulgecin A (BlgA) is a natural product of Pseudomonas mesoacidophila and a lytic transglycosolase inhibitor that works synergistically with β-lactams targeting PBP3 for Enterobacteriaceae. BlgA also weakly inhibits di-Zn 2+ metallo-β-lactamases like L1 of Stenotrophomonas maltophilia . We hypothesized that because of its unique mechanism of action, BlgA could restore susceptibility to carbapenems in carbapenem-resistant PSDA (CR-PSDA) and carbapenem-resistant ACB, as well as ACB resistant to sulbactam. A BlgA-containing extract was prepared using a previously published protocol. CR-PSDA clinical isolates demonstrating a variety of carbapenem resistance mechanisms (VIM-2 carbapenemases, efflux mechanisms, and AmpC producer expression) were characterized with agar dilution minimum inhibitory concentration (MIC) testing and polymerase chain reaction. Growth curves using these strains were prepared using meropenem, BlgA extract, and meropenem plus BlgA extract. A concentrated Blg A extract combined with low concentrations of meropenem, was able to inhibit the growth of clinical strains of CR-PSDA for strains that had meropenem MICs ≥8 mg/L by agar dilution, and a clinical strain of an OXA-24 producing ACB that had a meropenem MIC >32 mg/L and intermediate ampicillin/sulbactam susceptibility. Similar experiments were conducted on a TEM-1 producing ACB strain resistant to sulbactam. BlgA with ampicillin/sulbactam inhibited the growth of this organism. As in Enterobacteriaceae, BlgA appears to restore the efficacy of meropenem in suppressing the growth of CR-PSDA and carbapenem-resistant ACB strains with a variety of common carbapenem resistance mechanisms. BlgA extract also inhibits VIM-2 β-lactamase in vitro. BlgA may prove to be

  8. Mechanism of HIV-1 Resistance to an Electronically Constrained α-Helical Peptide Membrane Fusion Inhibitor.

    Science.gov (United States)

    Wu, Xiyuan; Liu, Zixuan; Ding, Xiaohui; Yu, Danwei; Wei, Huamian; Qin, Bo; Zhu, Yuanmei; Chong, Huihui; Cui, Sheng; He, Yuxian

    2018-04-01

    SC29EK is an electronically constrained α-helical peptide HIV-1 fusion inhibitor that is highly effective against both wild-type and enfuvirtide (T20)-resistant viruses. In this study, we focused on investigating the mechanism of HIV-1 resistance to SC29EK by two approaches. First, SC29EK-escaping HIV-1 variants were selected and characterized. Three mutant viruses, which possessed two (N43K/E49A) or three (Q39R/N43K/N126K and N43K/E49A/N126K) amino acid substitutions in the N- and C-terminal repeat regions of gp41 were identified as conferring high resistance to SC29EK and cross-resistance to the first-generation (T20 and C34) and newly designed (sifuvirtide, MT-SC29EK, and 2P23) fusion inhibitors. The resistance mutations could reduce the binding stability of SC29EK, impair viral Env-mediated cell fusion and entry, and change the conformation of the gp41 core structure. Further, we determined the crystal structure of SC29EK in complex with a target mimic peptide, which revealed the critical intra- and interhelical interactions underlying the mode of action of SC29EK and the genetic pathway to HIV-1 resistance. Taken together, the present data provide new insights into the structure and function of gp41 and the structure-activity relationship (SAR) of viral fusion inhibitors. IMPORTANCE T20 is the only membrane fusion inhibitor available for treatment of viral infection, but it has relatively low anti-HIV activity and genetic barriers for resistance, thus calling for new drugs blocking the viral fusion process. As an electronically constrained α-helical peptide, SC29EK is highly potent against both wild-type and T20-resistant HIV-1 strains. Here, we report the characterization of HIV-1 variants resistant to SC29EK and the crystal structure of SC29EK. The key mutations mediating high resistance to SC29EK and cross-resistance to the first and new generations of fusion inhibitors as well as the underlying mechanisms were identified. The crystal structure of SC29EK

  9. Systolic and Diastolic Left Ventricular Mechanics during and after Resistance Exercise.

    Science.gov (United States)

    Stöhr, Eric J; Stembridge, Mike; Shave, Rob; Samuel, T Jake; Stone, Keeron; Esformes, Joseph I

    2017-10-01

    To improve the current understanding of the impact of resistance exercise on the heart, by examining the acute responses of left ventricular (LV) strain, twist, and untwisting rate ("LV mechanics"). LV echocardiographic images were recorded in systole and diastole before, during and immediately after (7-12 s) double-leg press exercise at two intensities (30% and 60% of maximum strength, one-repetition maximum). Speckle tracking analysis generated LV strain, twist, and untwisting rate data. Additionally, beat-by-beat blood pressure was recorded and systemic vascular resistance (SVR) and LV wall stress were calculated. Responses in both exercise trials were statistically similar (P > 0.05). During effort, stroke volume decreased, whereas SVR and LV wall stress increased (P mechanics (P 0.05). Immediately after exercise, systolic LV mechanics returned to baseline levels (P mechanics, but increases diastolic mechanics after exercise, suggesting that resistance exercise has a differential impact on systolic and diastolic heart muscle function. The findings may explain why acute resistance exercise has been associated with reduced stroke volume but chronic exercise training may result in increased LV volumes.

  10. Molecular mechanisms of resistance to Rituximab and pharmacologic strategies for its circumvention.

    Science.gov (United States)

    Stolz, Claudia; Schuler, Martin

    2009-06-01

    The introduction of Rituximab has greatly improved therapeutic options for patients with B-cell non-Hodgkin lymphoma (B-NHL). However, a substantial fraction of patients with aggressive B-NHL fails first-line therapy, and most patients with relapsing indolent B-NHL eventually acquire Rituximab resistance. Molecular understanding of the underlying mechanisms facilitates the development of pharmacologic strategies to overcome resistance. Rituximab exerts its activity on CD20-expressing B-cells by indirect and direct effector mechanisms. Indirect mechanisms are complement-dependent cytotoxicity (CDC), and antibody-dependent cell-mediated cytotoxicity (ADCC). Direct activities, such as growth inhibition, induction of apoptosis and chemosensitisation, have been reported, but are less defined. Moreover, the relative contribution of CDC, ADCC and direct mechanisms to the activity of Rituximab in vivo is unclear. Down-regulation of CD20 and expression of complement inhibitors have been described as escape mechanisms in B-NHL. Recent reports suggest that deregulated phosphoinositide-3-kinase (PI3K)/Akt, mitogen-activated kinases (MAPK) and nuclear-factor kappaB (NF-kappaB), as well as up-regulation of anti-apoptotic proteins may determine the efficacy of Rituximab to kill B-NHL cells in vitro and in vivo. The latter signalling pathways are attractive targets for pharmacologic modulation of resistance to Rituximab. With the advent of new inhibitors and antibodies, rationally designed clinical trials addressing Rituximab resistance are feasible.

  11. Insertion torque versus mechanical resistance of mini-implants inserted in different cortical thickness.

    Science.gov (United States)

    Santos, Renata Faria; Ruellas, Antonio Carlos de Oliveira; Fernandes, Daniel Jogaib; Elias, Carlos Nelson

    2014-01-01

    This study aimed to measure insertion torque, tip mechanical resistance to fracture and transmucosal neck of mini-implants (MI) (Conexão Sistemas de PróteseT), as well as to analyze surface morphology. Mechanical tests were carried out to measure the insertion torque of MIs in different cortical thicknesses, and tip mechanical resistance to fracture as well as transmucosal neck of MIs. Surface morphology was assessed by scanning electron microscopy (SEM) before and after the mechanical tests. Values of mechanical resistance to fracture (22.14 N.cm and 54.95 N.cm) were higher and statistically different (P 0.05) to torsional fracture in the tip of MI (22.14 N.cm) when 3 mm cortical thickness (16.11 N.cm) and dense bone (23.95 N.cm) were used. Torsional fracture of the transmucosal neck (54.95 N.cm) was higher and statistically different (P mini-implants tested presented adequate surface morphology. The resistance of mini-implants to fracture safely allows placement in 1 and 2-mm cortical thickness. However, in 3-mm cortical thickness and dense bones, pre-drilling with a bur is recommended before insertion.

  12. Insertion torque versus mechanical resistance of mini-implants inserted in different cortical thickness

    Science.gov (United States)

    Santos, Renata de Faria; Ruellas, Antonio Carlos de Oliveira; Fernandes, Daniel Jogaib; Elias, Carlos Nelson

    2014-01-01

    Objective This study aimed to measure insertion torque, tip mechanical resistance to fracture and transmucosal neck of mini-implants (MI) (Conexão Sistemas de PróteseT), as well as to analyze surface morphology. Methods Mechanical tests were carried out to measure the insertion torque of MIs in different cortical thicknesses, and tip mechanical resistance to fracture as well as transmucosal neck of MIs. Surface morphology was assessed by scanning electron microscopy (SEM) before and after the mechanical tests. Results Values of mechanical resistance to fracture (22.14 N.cm and 54.95 N.cm) were higher and statistically different (P 0.05) to torsional fracture in the tip of MI (22.14 N.cm) when 3 mm cortical thickness (16.11 N.cm) and dense bone (23.95 N.cm) were used. Torsional fracture of the transmucosal neck (54.95 N.cm) was higher and statistically different (P mini-implants tested presented adequate surface morphology. The resistance of mini-implants to fracture safely allows placement in 1 and 2-mm cortical thickness. However, in 3-mm cortical thickness and dense bones, pre-drilling with a bur is recommended before insertion. PMID:25162571

  13. Improved resistive switching characteristics in Ni/SiNx/p++-Si devices by tuning x

    Science.gov (United States)

    Kim, Sungjun; Chang, Yao-Feng; Kim, Min-Hwi; Park, Byung-Gook

    2017-07-01

    This letter studies the effect of the negative-set on the resistive switching performances of CMOS-compatible Ni/SiNx/p++-Si resistive memory devices by simply tuning x. A Ni/SiN1.07/p++-Si device showed lower power switching (20 μW) and better endurance cycles (103) compared to a Ni/SiN0.82/p++-Si device because of the improved negative set behavior and initially lower set and reset currents. In addition, we achieved fast switching speed for set (200 ns) and reset (100 ns) processes in the Ni/SiN1.07/p++-Si device. For the Ni/SiN1.07/p++-Si device, fine adjustment of resistance values is attainable by varying the pulse amplitude and width due to the gradual reset switching characteristics. The barrier-height-dependent conduction model is proposed to explain the change in the current level with the x value.

  14. Molluscicidal activities of curcumin-nisin polylactic acid nanoparticle on Biomphalaria pfeifferi.

    Science.gov (United States)

    Omobhude, Michael E; Morenikeji, Olajumoke A; Oyeyemi, Oyetunde T

    2017-08-01

    Snail intermediate host control is a widely canvassed strategy for schistosomiasis control in endemic countries. While there have been increasing studies on the search for potent molluscicides in the past years, the use of nanoparticulate agents as molluscicides is yet to gain wide attention. The aim of this study was to assess the molluscicidal potential of curcumin-nisin poly lactic acid (PLA) entrapped nanoparticle (CurNisNp) against Biomphalaria pfeifferi, a snail intermediate host for Schistosoma mansoni. CurNisNp formulated by double emulsion method was tested against the young adults, molluscicidal activities on different developmental stages of B. pfeifferi. It is therefore recommended that the formulation be more optimised to give a nanoparticle with a narrow range monodispersed PDI for better drug distribution and eventual greater molluscicidal activities.

  15. Perinatal acquisition of drug-resistant HIV-1 infection: mechanisms and long-term outcome

    Directory of Open Access Journals (Sweden)

    Dollfus Catherine

    2009-09-01

    Full Text Available Abstract Background Primary-HIV-1-infection in newborns that occurs under antiretroviral prophylaxis that is a high risk of drug-resistance acquisition. We examine the frequency and the mechanisms of resistance acquisition at the time of infection in newborns. Patients and Methods We studied HIV-1-infected infants born between 01 January 1997 and 31 December 2004 and enrolled in the ANRS-EPF cohort. HIV-1-RNA and HIV-1-DNA samples obtained perinatally from the newborn and mother were subjected to population-based and clonal analyses of drug resistance. If positive, serial samples were obtained from the child for resistance testing. Results Ninety-two HIV-1-infected infants were born during the study period. Samples were obtained from 32 mother-child pairs and from another 28 newborns. Drug resistance was detected in 12 newborns (20%: drug resistance to nucleoside reverse transcriptase inhibitors was seen in 10 cases, non-nucleoside reverse transcriptase inhibitors in two cases, and protease inhibitors in one case. For 9 children, the detection of the same resistance mutations in mothers' samples (6 among 10 available and in newborn lymphocytes (6/8 suggests that the newborn was initially infected by a drug-resistant strain. Resistance variants were either transmitted from mother-to-child or selected during subsequent temporal exposure under suboptimal perinatal prophylaxis. Follow-up studies of the infants showed that the resistance pattern remained stable over time, regardless of antiretroviral therapy, suggesting the early cellular archiving of resistant viruses. The absence of resistance in the mother of the other three children (3/10 and neonatal lymphocytes (2/8 suggests that the newborns were infected by a wild-type strain without long-term persistence of resistance when suboptimal prophylaxis was stopped. Conclusion This study confirms the importance of early resistance genotyping of HIV-1-infected newborns. In most cases (75%, drug

  16. Strengthening mechanisms and mechanical properties of high interstitial stainless steel for drill collar and its corrosion resistance

    Science.gov (United States)

    Lee, Eunkyung

    Two types (CN66, CN71) of high interstitial stainless steels (HISSs) were investigated for down-hole application in sour gas well environments. Experiments were designed to identify factors that have a significant effect on mechanical properties. The three factors examined in the study were carbon + nitrogen content (0.66 or 0.71 mass %), cooling rate in quenching (air or water), and heat treatment time (2 or 4 hours). The results showed that the cooling rate, C+N content, and the two-factor interaction of these variables have a significant effect on the mechanical properties of HISSs. Based on the statistical analysis results on mechanical properties, extensive analyses were undertaken to understand the strengthening mechanisms of HISSs. Microstructure analysis revealed that a pearlite phase with a high carbide and/or nitride content is dissolved in the matrix by heat treatment at 1,200 ºC which is considered the dissolution to increase the concentration of interstitial elements in steels. The distribution of elements in HISSs was investigated by quantitative mapping using EPMA, which showed that the high carbon concentration (carbide/cementite) area was decreased by increases in both the cooling rate and C+N content. The ferrite volume fraction of each specimen is increased by an increase in cooling rate, because there is insufficient time to form austenite from retained ferrite. The lattice expansion of HISS was investigated by the calculation of lattice parameters under various conditions, and these investigations confirm the solid solution strengthening effect on HISSs. CN66 with heat treatment at fast cooling has the highest wear resistance; a finding that was consistent with hardening mechanisms that occur due to an increased ferrite volume fraction. In addition, precipitates on the surface and the chemical bonding of chromium were investigated. As the amount of CrN bonding increased, the wear resistance also increased. This study also assessed the

  17. Nonoclusive thrombosis of mechanical mitral valve prosthesis caused by inadequate treatment of anticoagulant therapy resistance

    Directory of Open Access Journals (Sweden)

    Ivanović Branislava

    2008-01-01

    Full Text Available Background. Oral anticoagulants have been used in the prevention of thromboembolic complications for over six decades. A rare, but possible problem in the application of these medications could be resistance to them. Case report. We presented a patient with nonocclusive thrombosis of the mechanical mitral prosthesis due to inadequately treated resistance to peroral anticoagulant therapy. Resistance to oral anticoagulant medications was proven by an increased dosage of warfarin up to 20 mg and, after that, acenokumarol to 15 mg over ten days which did not lead to an increase in the international normalized ratio (INR value over 1.2. On the basis of information that she did not take food rich in vitamin K or medications which could reduce effects of oral anticoagulants, and that she did not have additional illnesses and conditions that could cause an inadequate response to anticoagulant therapy, it was circumstantially concluded that this was a hereditary form of resistance. Because of the existing mechanical prosthetics on the mitral position, low molecular heparin has been introduced into the therapy. The patient reduced it on her own initiative, leading to nonocclusive valvular thrombosis. Conclusion. When associated complications like absolute arrhithmia does not exist, the finding of resistance to oral anticoagulant agents is an indication for the replacement of a mechanical prosthetic with a biological one which has been done in this patients.

  18. Clostridium difficile Infections: A Global Overview of Drug Sensitivity and Resistance Mechanisms

    Directory of Open Access Journals (Sweden)

    Saeed S. Banawas

    2018-01-01

    Full Text Available Clostridium difficile (C. difficile is the most prevalent causative pathogen of healthcare-associated diarrhea. Notably, over the past 10 years, the number of Clostridium difficile outbreaks has increased with the rate of morbidity and mortality. The occurrence and spread of C. difficile strains that are resistant to multiple antimicrobial drugs complicate prevention as well as potential treatment options. Most C. difficile isolates are still susceptible to metronidazole and vancomycin. Incidences of C. difficile resistance to other antimicrobial drugs have also been reported. Most of the antibiotics correlated with C. difficile infection (CDI, such as ampicillin, amoxicillin, cephalosporins, clindamycin, and fluoroquinolones, continue to be associated with the highest risk for CDI. Still, the detailed mechanism of resistance to metronidazole or vancomycin is not clear. Alternation in the target sites of the antibiotics is the main mechanism of erythromycin, fluoroquinolone, and rifamycin resistance in C. difficile. In this review, different antimicrobial agents are discussed and C. difficile resistance patterns and their mechanism of survival are summarized.

  19. Molecular Mechanisms and Clinical Impact of Acquired and Intrinsic Fosfomycin Resistance

    Directory of Open Access Journals (Sweden)

    Alexandro Rodríguez-Rojas

    2013-04-01

    Full Text Available Bacterial infections caused by antibiotic-resistant isolates have become a major health problem in recent years, since they are very difficult to treat, leading to an increase in morbidity and mortality. Fosfomycin is a broad-spectrum bactericidal antibiotic that inhibits cell wall biosynthesis in both Gram-negative and Gram-positive bacteria. This antibiotic has a unique mechanism of action and inhibits the initial step in peptidoglycan biosynthesis by blocking the enzyme, MurA. Fosfomycin has been used successfully for the treatment of urinary tract infections for a long time, but the increased emergence of antibiotic resistance has made fosfomycin a suitable candidate for the treatment of infections caused by multidrug-resistant pathogens, especially in combination with other therapeutic partners. The acquisition of fosfomycin resistance could threaten the reintroduction of this antibiotic for the treatment of bacterial infection. Here, we analyse the mechanism of action and molecular mechanisms for the development of fosfomycin resistance, including the modification of the antibiotic target, reduced antibiotic uptake and antibiotic inactivation. In addition, we describe the role of each pathway in clinical isolates.

  20. Multifaceted mechanisms of HIV inhibition and resistance to CCR5 inhibitors PSC-RANTES and Maraviroc.

    Science.gov (United States)

    Lobritz, Michael A; Ratcliff, Annette N; Marozsan, Andre J; Dudley, Dawn M; Tilton, John C; Arts, Eric J

    2013-06-01

    Small-molecule CCR5 antagonists, such as maraviroc (MVC), likely block HIV-1 through an allosteric, noncompetitive inhibition mechanism, whereas inhibition by agonists such as PSC-RANTES is less defined and may involve receptor removal by cell surface downregulation, competitive inhibition by occluding the HIV-1 envelope binding, and/or allosteric effects by altering CCR5 conformation. We explored the inhibitory mechanisms of maraviroc and PSC-RANTES by employing pairs of virus clones with differential sensitivities to these inhibitors. Intrinsic PSC-RANTES-resistant virus (YA versus RT) or those selected in PSC-RANTES treated macaques (M584 versus P3-4) only displayed resistance in multiple-cycle assays or with a CCR5 mutant that cannot be downregulated. In single-cycle assays, these HIV-1 clones displayed equal sensitivity to PSC-RANTES inhibition, suggesting effective receptor downregulation. Prolonged PSC-RANTES exposure resulted in desensitization of the receptor to internalization such that increasing virus concentration (substrate) could saturate the receptors and overcome PSC-RANTES inhibition. In contrast, resistance to MVC was observed with the MVC-resistant HIV-1 (R3 versus S2) in both multiple- and single-cycle assays and with altered virus concentrations, which is indicative of allosteric inhibition. MVC could also mediate inhibition and possibly resistance through competitive mechanisms.

  1. Spanish multicenter study of the epidemiology and mechanisms of amoxicillin-clavulanate resistance in Escherichia coli.

    Science.gov (United States)

    Ortega, Adriana; Oteo, Jesús; Aranzamendi-Zaldumbide, Maitane; Bartolomé, Rosa M; Bou, Germán; Cercenado, Emilia; Conejo, M Carmen; González-López, Juan José; Marín, Mercedes; Martínez-Martínez, Luis; Merino, María; Navarro, Ferran; Oliver, Antonio; Pascual, Alvaro; Rivera, Alba; Rodríguez-Baño, Jesús; Weber, Irene; Aracil, Belén; Campos, José

    2012-07-01

    We conducted a prospective multicenter study in Spain to characterize the mechanisms of resistance to amoxicillin-clavulanate (AMC) in Escherichia coli. Up to 44 AMC-resistant E. coli isolates (MIC ≥ 32/16 μg/ml) were collected at each of the seven participant hospitals. Resistance mechanisms were characterized by PCR and sequencing. Molecular epidemiology was studied by pulsed-field gel electrophoresis (PFGE) and by multilocus sequence typing. Overall AMC resistance was 9.3%. The resistance mechanisms detected in the 257 AMC-resistant isolates were OXA-1 production (26.1%), hyperproduction of penicillinase (22.6%), production of plasmidic AmpC (19.5%), hyperproduction of chromosomic AmpC (18.3%), and production of inhibitor-resistant TEM (IRT) (17.5%). The IRTs identified were TEM-40 (33.3%), TEM-30 (28.9%), TEM-33 (11.1%), TEM-32 (4.4%), TEM-34 (4.4%), TEM-35 (2.2%), TEM-54 (2.2%), TEM-76 (2.2%), TEM-79 (2.2%), and the new TEM-185 (8.8%). By PFGE, a high degree of genetic diversity was observed although two well-defined clusters were detected in the OXA-1-producing isolates: the C1 cluster consisting of 19 phylogroup A/sequence type 88 [ST88] isolates and the C2 cluster consisting of 19 phylogroup B2/ST131 isolates (16 of them producing CTX-M-15). Each of the clusters was detected in six different hospitals. In total, 21.8% of the isolates were serotype O25b/phylogroup B2 (O25b/B2). AMC resistance in E. coli is widespread in Spain at the hospital and community levels. A high prevalence of OXA-1 was found. Although resistant isolates were genetically diverse, clonality was linked to OXA-1-producing isolates of the STs 88 and 131. Dissemination of IRTs was frequent, and the epidemic O25b/B2/ST131 clone carried many different mechanisms of AMC resistance.

  2. Ester-free Thiol-X Resins: New Materials with Enhanced Mechanical Behavior and Solvent Resistance

    OpenAIRE

    Podgórski, Maciej; Becka, Eftalda; Chatani, Shunsuke; Claudino, Mauro; Bowman, Christopher N.

    2015-01-01

    A series of thiol-Michael and radical thiol-ene network polymers were successfully prepared from ester-free as well as ester-containing monomer formulations. Polymerization reaction rates, dynamic mechanical analysis, and solvent resistance experiments were performed and compared between compositions with varied ester loading. The incorporation of ester-free alkyl thiol, vinyl sulfone and allylic monomers significantly improved the mechanical properties when compared with commercial, mercapto...

  3. Biochemical mechanisms of insecticide resistance in field population of Dengue vector Aedes aegypti (Diptera: Culicidae.

    Directory of Open Access Journals (Sweden)

    R. Muthusamy

    2014-03-01

    Full Text Available Insecticide resistance has been known to be prevalent in several insect species including mosquito. It has become a major problem in vector control programme due to pesticide resistance through detoxification enzymes. The present study investigated the toxicity of Ae. aegypti to organophosphates and pyrethroid insecticide and biochemical mechanisms involved in insecticide resistance in larval population. Larval bioassay revealed an LC50 value of 0.734 ppm for dichlorvos and 1.140 ppm for λ-cyhalothrin exposure. Biochemical assay revealed increased activity of AChE (0.3 µmole/mg protein and GST in dichlorvos (1-1.5 µmole/mg protein treatment and esterase activity in λ-cyhalothrin treated compared to control activity. These studies suggest that AChE and GST is associated with organophosphate and esterase associated with pyrethroid resistance in Ae. aegypti.

  4. [Effects and mechanisms of plant roots on slope reinforcement and soil erosion resistance: a research review].

    Science.gov (United States)

    Xiong, Yan-Mei; Xia, Han-Ping; Li, Zhi-An; Cai, Xi-An

    2007-04-01

    Plant roots play an important role in resisting the shallow landslip and topsoil erosion of slopes by raising soil shear strength. Among the models in interpreting the mechanisms of slope reinforcement by plant roots, Wu-Waldron model is a widely accepted one. In this model, the reinforced soil strength by plant roots is positively proportional to average root tensile strength and root area ratio, the two most important factors in evaluating slope reinforcement effect of plant roots. It was found that soil erosion resistance increased with the number of plant roots, though no consistent quantitative functional relationship was observed between them. The increase of soil erosion resistance by plant roots was mainly through the actions of fiber roots less than 1 mm in diameter, while fiber roots enhanced the soil stability to resist water dispersion via increasing the number and diameter of soil water-stable aggregates. Fine roots could also improve soil permeability effectively to decrease runoff and weaken soil erosion.

  5. Some resistance mechanisms to ultraviolet radiation; Algunos mecanismos de resistencia a radiacion ultravioleta

    Energy Technology Data Exchange (ETDEWEB)

    Alcantara D, D. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2002-12-15

    The cyclical exposure of bacterial cells to the ultraviolet light (UV) it has as consequence an increment in the resistance to the lethal effects of this type of radiation, increment that happens as a result of a selection process of favorable genetic mutations induced by the same UV light. With object to study the reproducibility of the genetic changes and the associate mechanisms to the resistance to UV in the bacteria Escherichia coli, was irradiated cyclically with UV light five different derived cultures of a single clone, being obtained five stumps with different resistance grades. The genetic mapping Hfr revealed that so much the mutation events like of selection that took place during the adaptation to the UV irradiation, happened of random manner, that is to say, each one of the resistant stumps it is the result of the unspecified selection of mutations arisen at random in different genes related with the repair and duplication of the DNA. (Author)

  6. Effect of Al on the mechanical properties and corrosion resistance of Pb-Al alloy

    Science.gov (United States)

    LU, Zhicheng; LIU, Zhenlin; LI, Yongliang; WU, Dan; WANG, Fuming

    2017-05-01

    A set of binary Pb-Al alloys with different Al contents were designed in this work. The mechanical properties and corrosion resistance of Pb-Al alloys were investigated with help of tensile test, Charpy V-notch impact test and salt spray corrosion test (SSCT). And the microstructure was observed by optical microscopy. The results showed that microstructure of all alloys were twin structure, and the twin structure was gradually refined with the increase of Al content. Al dissolved in matrix could significantly improve the tensile strength, impact energy and corrosion resistance. However, a higher content of Al would harm the mechanical properties and corrosion resistance. It may be due to the heterogeneous precipitation of Al rich phase.

  7. Targeting the Mechanisms of Resistance to Chemotherapy and Radiotherapy with the Cancer Stem Cell Hypothesis

    Directory of Open Access Journals (Sweden)

    Ryan Morrison

    2011-01-01

    Full Text Available Despite advances in treatment, cancer remains the 2nd most common cause of death in the United States. Poor cure rates may result from the ability of cancer to recur and spread after initial therapies have seemingly eliminated detectable signs of disease. A growing body of evidence supports a role for cancer stem cells (CSCs in tumor regrowth and spread after initial treatment. Thus, targeting CSCs in combination with traditional induction therapies may improve treatment outcomes and survival rates. Unfortunately, CSCs tend to be resistant to chemo- and radiation therapy, and a better understanding of the mechanisms underlying CSC resistance to treatment is necessary. This paper provides an update on evidence that supports a fundamental role for CSCs in cancer progression, summarizes potential mechanisms of CSC resistance to treatment, and discusses classes of drugs currently in preclinical or clinical testing that show promise at targeting CSCs.

  8. Resistance of transgenic eggplant carrying the oryzacystatin gene to Mechanitis polymnia and Mechanitis lysimnia - DOI: 10.4025/actasciagron.v27i4.1345

    OpenAIRE

    Ribeiro, Ana Paula de Oliveira; UFV; Otoni, Wagner Campos; UFV; Picanço, Marcelo Coutinho; Universidade Federal de Viçosa, Centro de Ciências Biológicas e da Saúde; Galvan, Tederson Luiz; UFV; Pereira, Eliseu José Guedes; UFV; Picoli, Edgard Augusto de Toledo; UFV; Silva, Derly José Henriques da; UFV

    2008-01-01

    This research aimed to evaluate the resistance of transgenic eggplant (Solanum melongena) carrying the oryzacystatin gene to Mechanitis polymnia L. and Mechanitis lysimnia Fabr. (Lepidoptera: Nymphalidae). The leaf area consumed, the mortality and duration of the larval and pupal phases of M. polymnia and M. lysimnia were evaluated. Results showed the transgenic eggplant is not resistant to Lepidoptera M. polymnia and M. lysimnia Esta pesquisa objetivou avaliar a resistência da berinjela (...

  9. Emergence and Spread of A Plasmid-Mediated Polymyxin Resistance Mechanism, MCR-1: Are Bacteria Winning?

    Directory of Open Access Journals (Sweden)

    Chao Yang

    2015-12-01

    Full Text Available The report of the emergence of mcr-1, the first plasmid-mediated polymyxin resistance mechanism, in Enterobacteriaceae in November 2015 challenged our last psychological line of defense. However, we still trusted that this resistance factor had not spread globally. One month later, in December 2015, the detection of mcr-1 in an Escherichia coliisolate from a septicemic patient in Denmark and in five E. coli isolates from imported chicken meat really defeated us. The worst news was that one of the chicken meat isolates belonged to ST131, a spreading epidemic sequence type. In China, 15%-21% of E. coli strains isolated from raw meat and animals carried mcr-1, and about 1% of patient isolates carried this gene, indicating that E. coli carrying this plasmid is not a rare phenomenon. This gene is transferable by conjugation and can be maintained in Klebsiella pneumonia and Pseudomonas aeruginosa, suggesting the risk of transfer between different bacterial genera. The good news is that the strains carrying mcr-1 do not contain genes for pan-resistance profiles, although some Danish strains contain 15 different resistance genes, including genes for extended-spectrum beta-lactam antibiotics, and gene mutations leading to high-level fluoroquinolone resistance. If the mcr-1-bearing strains acquire multidrug resistance, extensive drug resistance, or pandrug resistance, no antibiotic drugs will be available with which clinicians can treat infected patients. Therefore, the use of antibiotics in both hospitals and the animal breeding industry must be strictly regulated. The origin of mcr-1 may be associated with the wide use of colistin in agriculture. There is no evidence that the Danish mcr-1 gene spread from China. Therefore, it is likely that mcr-1 genes originated in multiple sites simultaneously under the pressure of colistin use, because India and Denmark are the world’ s greatest users of this antibiotic. More surveys must be conducted in different

  10. Molecular survey of pyrethroid resistance mechanisms in Mexican field populations of Rhipicephalus (Boophilus) microplus

    Science.gov (United States)

    Susceptibility to synthetic pyrethroids (SP´s) and the role of two major resistance mechanisms were evaluated in Mexican Rhipicephalus microplus tick populations. Larval packet test (LPT), knock-down (kdr) PCR allele-specific assay (PASA) and esterase activity assays were conducted in tick populatio...

  11. Mechanism of Action of Substituted Indanones in Multidrug Resistant Breast Cancer

    National Research Council Canada - National Science Library

    Leoni, Lorenzo

    2002-01-01

    ... (Cancer Res 2001 Oct 1 61(1 9):7248-54) - analyzed the indanocine-resistant stable cell line - identified the potential indanocine-binding site on tubulin - continued the animal testing of indanocine - studies the pro-apoptotic mechanism...

  12. SEVERAL MECHANISMS OF MERCURY RESISTANCE FOUND IN SOIL ISOLATES FROM PAVLODAR, KAZAKHSTAN

    Science.gov (United States)

    Abdrashitova, Svetlava A., M.A. Ilyushchenko, A. Yu Kalmykv, S.A. Aitkeldieva, Wendy J. Davis-Hoover and Richard Devereux. In press. Several Mechanisms of Mercury Resistance Found in Soil Isolates from Pavlodar, Kazakhstan (Abstract). To be presented at the Battelle Conference on...

  13. Mechanisms of methicillin resistance in Staphylococcus aureus and methods for laboratory detection.

    Science.gov (United States)

    Jorgensen, J H

    1991-01-01

    Three distinctly different mechanisms of methicillin resistance have been described in Staphylococcus aureus. The best-documented and probably most important mechanism is production of a unique, low affinity penicillin-binding protein, PBP 2a. Strains possessing PBP 2a are resistant to methicillin, oxacillin, and probably all other currently available beta-lactam antibiotics. Two additional mechanisms of reduced susceptibility to methicillin have been described. Borderline resistance (BORSA) to the semi-synthetic penicillins has been attributed to the hyperproduction of normal staphylococcal beta-lactamase. A third mechanism has recently been advanced that describes an intermediate level of resistance to methicillin due to production of modified, normal PBPs with reduced affinity for beta-lactams (MODSA). Little is known regarding the prevalence or clinical significance of the BORSA and MODSA strains. The most reliable in vitro susceptibility test methods for detecting MRSA (strains possessing PBP 2a) include the microdilution minimum inhibitory concentration (MIC) test (with 2% NaCl supplemented broth), the oxacillin agar screen plate test (incorporating 6 micrograms/ml oxacillin in 4% NaCl supplemented agar), and the National Committee for Clinical Laboratory Standards (NCCLS) disk diffusion test with oxacillin. All three methods use direct inoculum preparation and incubation of tests at 35 degrees C for a full 24 hours.

  14. Evaluating the role of root citrate exudation as a mechanism of aluminium resistance in maize genotypes

    NARCIS (Netherlands)

    Mariano, E.D.; Keltjens, W.G.

    2003-01-01

    Organic anion exudation by roots as a mechanism of aluminium (Al) resistance has been intensively studied lately. In the present study, we evaluated qualitative and quantitative aspects of root exudation of organic anions in maize genotypes of distinct sensitivity to Al in response to Al exposure.

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

    Science.gov (United States)

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

    2006-01-01

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

  16. Nitrogen Metabolim in Sheep Fed Hay-Based Diet Supplemented with Yucca schidigera with or without Nisin

    OpenAIRE

    B Santoso

    2005-01-01

    Empat ekor domba yang berfistula pada bagian rumen digunakan pada rancangan Bujur sangkar latin 3 x 3. penelitian ini bertujuan untuk mengetahui pengaruh suplementasi Yucca schidigera dengan atau tanpa nisin terhadap penggunaan nitrogen, konsentrasi amonia dalam rumen, konsentrasi nitrogen urea dalam plasma, suplai nitrogen mikroba pada domba yang diberi pakan basal hay rumput timothy dan konsentrat. Tiga perlakuan pakan yaitu pakan basal (kontrol), pakan basal + Yucca schidigera 240 ppm (yuc...

  17. Modeling growth of Alicyclobacillus acidoterrestris DSM 3922 type strain vegetative cells in the apple juice with nisin and lysozyme

    Directory of Open Access Journals (Sweden)

    Celenk Molva

    2017-05-01

    Full Text Available In the present study, the effect of storage temperature on A. acidoterrestris DSM 3922 cells (105 CFU/mL was examined during growth in reconstituted apple juice (pH 3.8, °Brix 11.3 containing nisin (0–100 IU/mL and lysozyme (0–100 mg/L. The growth curves were obtained at three temperatures of 27, 35 and 43 °C using absorbance data (OD600 nm. Based on the results, the minimal inhibitory concentrations (MICs of nisin were found as 10 IU/mL at all tested temperatures. On the other hand, increasing the temperature decreased the amount of lysozyme for growth inhibition. The MICs of lysozyme were found as 10, 2.5 and 1.25 mg/L at 27, 35 and 43 °C, respectively. At selected non-inhibitory doses, nisin (1.25–5 IU/mL and lysozyme (0.3–2.5 mg/L prolonged the lag time compared to the controls at the corresponding temperatures. In addition, there was a strong linear relationship between the lag time and lysozyme concentrations at 27 and 35 °C (R2 > 0.98. The results of this study demonstrated that both nisin and lysozyme could be used to inhibit the growth of A. acidoterrestris cells in the apple juice. The results also indicated that the growth parameters were variable depending on the storage temperature and the type of the antimicrobial agent used in the apple juice.

  18. Investigating the molecular mechanisms of organophosphate and pyrethroid resistance in the fall armyworm Spodoptera frugiperda.

    Directory of Open Access Journals (Sweden)

    Renato A Carvalho

    Full Text Available The fall armyworm Spodoptera frugiperda is an economically important pest of small grain crops that occurs in all maize growing regions of the Americas. The intensive use of chemical pesticides for its control has led to the selection of resistant populations, however, to date, the molecular mechanisms underlying resistance have not been characterised. In this study the mechanisms involved in the resistance of two S. frugiperda strains collected in Brazil to chlorpyrifos (OP strain or lambda-cyhalothrin (PYR strain were investigated using molecular and genomic approaches. To examine the possible role of target-site insensitivity the genes encoding the organophosphate (acetylcholinesterase, AChE and pyrethroid (voltage-gated sodium channel, VGSC target-site proteins were PCR amplified. Sequencing of the S. frugiperda ace-1 gene identified several nucleotide changes in the OP strain when compared to a susceptible reference strain (SUS. These result in three amino acid substitutions, A201S, G227A and F290V, that have all been shown previously to confer organophosphate resistance in several other insect species. Sequencing of the gene encoding the VGSC in the PYR strain, identified mutations that result in three amino acid substitutions, T929I, L932F and L1014F, all of which have been shown previously to confer knockdown/super knockdown-type resistance in several arthropod species. To investigate the possible role of metabolic detoxification in the resistant phenotype of the OP and PYR stains all EST sequences available for S. frugiperda were used to design a gene-expression microarray. This was then used to compare gene expression in the resistant strains with the susceptible reference strain. Members of several gene families, previously implicated in metabolic resistance in other insects were found to be overexpressed in the resistant strains including glutathione S-transferases, cytochrome P450s and carboxylesterases. Taken together these results

  19. Deltamethrin Resistance Mechanisms in Aedes aegypti Populations from Three French Overseas Territories Worldwide.

    Directory of Open Access Journals (Sweden)

    Isabelle Dusfour

    2015-11-01

    Full Text Available Aedes aegypti is a cosmopolite mosquito, vector of arboviruses. The worldwide studies of its insecticide resistance have demonstrated a strong loss of susceptibility to pyrethroids, the major class of insecticide used for vector control. French overseas territories such as French Guiana (South America, Guadeloupe islands (Lesser Antilles as well as New Caledonia (Pacific Ocean, have encountered such resistance.We initiated a research program on the pyrethroid resistance in French Guiana, Guadeloupe and New Caledonia. Aedes aegypti populations were tested for their deltamethrin resistance level then screened by an improved microarray developed to specifically study metabolic resistance mechanisms. Cytochrome P450 genes were implicated in conferring resistance. CYP6BB2, CYP6M11, CYP6N12, CYP9J9, CYP9J10 and CCE3 genes were upregulated in the resistant populations and were common to other populations at a regional scale. The implication of these genes in resistance phenomenon is therefore strongly suggested. Other genes from detoxification pathways were also differentially regulated. Screening for target site mutations on the voltage-gated sodium channel gene demonstrated the presence of I1016 and C1534.This study highlighted the presence of a common set of differentially up-regulated detoxifying genes, mainly cytochrome P450 genes in all three populations. GUA and GUY populations shared a higher number of those genes compared to CAL. Two kdr mutations well known to be associated to pyrethroid resistance were also detected in those two populations but not in CAL. Different selective pressures and genetic backgrounds can explain such differences. These results are also compared with those obtained from other parts of the world and are discussed in the context of integrative research on vector competence.

  20. Deltamethrin Resistance Mechanisms in Aedes aegypti Populations from Three French Overseas Territories Worldwide.

    Science.gov (United States)

    Dusfour, Isabelle; Zorrilla, Pilar; Guidez, Amandine; Issaly, Jean; Girod, Romain; Guillaumot, Laurent; Robello, Carlos; Strode, Clare

    2015-11-01

    Aedes aegypti is a cosmopolite mosquito, vector of arboviruses. The worldwide studies of its insecticide resistance have demonstrated a strong loss of susceptibility to pyrethroids, the major class of insecticide used for vector control. French overseas territories such as French Guiana (South America), Guadeloupe islands (Lesser Antilles) as well as New Caledonia (Pacific Ocean), have encountered such resistance. We initiated a research program on the pyrethroid resistance in French Guiana, Guadeloupe and New Caledonia. Aedes aegypti populations were tested for their deltamethrin resistance level then screened by an improved microarray developed to specifically study metabolic resistance mechanisms. Cytochrome P450 genes were implicated in conferring resistance. CYP6BB2, CYP6M11, CYP6N12, CYP9J9, CYP9J10 and CCE3 genes were upregulated in the resistant populations and were common to other populations at a regional scale. The implication of these genes in resistance phenomenon is therefore strongly suggested. Other genes from detoxification pathways were also differentially regulated. Screening for target site mutations on the voltage-gated sodium channel gene demonstrated the presence of I1016 and C1534. This study highlighted the presence of a common set of differentially up-regulated detoxifying genes, mainly cytochrome P450 genes in all three populations. GUA and GUY populations shared a higher number of those genes compared to CAL. Two kdr mutations well known to be associated to pyrethroid resistance were also detected in those two populations but not in CAL. Different selective pressures and genetic backgrounds can explain such differences. These results are also compared with those obtained from other parts of the world and are discussed in the context of integrative research on vector competence.

  1. Acinetobacter spp. Infections in Malaysia: A Review of Antimicrobial Resistance Trends, Mechanisms and Epidemiology

    Directory of Open Access Journals (Sweden)

    Farahiyah Mohd. Rani

    2017-12-01

    Full Text Available Acinetobacter spp. are important nosocomial pathogens, in particular the Acinetobacter baumannii-calcoaceticus complex, which have become a global public health threat due to increasing resistance to carbapenems and almost all other antimicrobial compounds. High rates of resistance have been reported among countries in Southeast Asia, including Malaysia. In this review, we examine the antimicrobial resistance profiles of Acinetobacter spp. hospital isolates from Malaysia over a period of nearly three decades (1987–2016 with data obtained from various peer-reviewed publications as well as the Malaysian National Surveillance on Antibiotic Resistance (NSAR. NSAR data indicated that for most antimicrobial compounds, including carbapenems, the peak resistance rates were reached around 2008–2009 and thereafter, rates have remained fairly constant (e.g., 50–60% for carbapenems. Individual reports from various hospitals in Peninsular Malaysia do not always reflect the nationwide resistance rates and often showed higher rates of resistance. We also reviewed the epidemiology and mechanisms of resistance that have been investigated in Malaysian Acinetobacter spp. isolates, particularly carbapenem resistance and found that blaOXA-23 is the most prevalent acquired carbapenemase-encoding gene. From the very few published reports and whole genome sequences that are available, most of the Acinetobacter spp. isolates from Malaysia belonged to the Global Clone 2 (GC2 CC92 group with ST195 being the predominant sequence type. The quality of data and analysis in the national surveillance reports could be improved and more molecular epidemiology and genomics studies need to be carried out for further in-depth understanding of Malaysian Acinetobacter spp. isolates.

  2. A novel substrate-based HIV-1 protease inhibitor drug resistance mechanism.

    Directory of Open Access Journals (Sweden)

    Monique Nijhuis

    2007-01-01

    Full Text Available BACKGROUND: HIV protease inhibitor (PI therapy results in the rapid selection of drug resistant viral variants harbouring one or two substitutions in the viral protease. To combat PI resistance development, two approaches have been developed. The first is to increase the level of PI in the plasma of the patient, and the second is to develop novel PI with high potency against the known PI-resistant HIV protease variants. Both approaches share the requirement for a considerable increase in the number of protease mutations to lead to clinical resistance, thereby increasing the genetic barrier. We investigated whether HIV could yet again find a way to become less susceptible to these novel inhibitors. METHODS AND FINDINGS: We have performed in vitro selection experiments using a novel PI with an increased genetic barrier (RO033-4649 and demonstrated selection of three viruses 4- to 8-fold resistant to all PI compared to wild type. These PI-resistant viruses did not have a single substitution in the viral protease. Full genomic sequencing revealed the presence of NC/p1 cleavage site substitutions in the viral Gag polyprotein (K436E and/or I437T/V in all three resistant viruses. These changes, when introduced in a reference strain, conferred PI resistance. The mechanism leading to PI resistance is enhancement of the processing efficiency of the altered substrate by wild-type protease. Analysis of genotypic and phenotypic resistance profiles of 28,000 clinical isolates demonstrated the presence of these NC/p1 cleavage site mutations in some clinical samples (codon 431 substitutions in 13%, codon 436 substitutions in 8%, and codon 437 substitutions in 10%. Moreover, these cleavage site substitutions were highly significantly associated with reduced susceptibility to PI in clinical isolates lacking primary protease mutations. Furthermore, we used data from a clinical trial (NARVAL, ANRS 088 to demonstrate that these NC/p1 cleavage site changes are

  3. Utilization of Condensed Distillers Solubles as Nutrient Supplement for Production of Nisin and Lactic Acid from Whey

    Science.gov (United States)

    Liu, Chuanbin; Hu, Bo; Chen, Shulin; Glass, Richard W.

    The major challenge associated with the rapid growth of the ethanol industry is the usage of the coproducts, i.e., condensed distillers solubles (CDS) and distillers dried grains, which are currently sold as animal feed supplements. As the growth of the livestock industries remains flat, alternative usage of these coproducts is urgently needed. CDS is obtained after the removal of ethanol by distillation from the yeast fermentation of a grain or a grain mixture by condensing the thin stillage fraction to semisolid. In this work, CDS was first characterized and yeast biomass was proven to be the major component of CDS. CDS contained 7.50% crude protein but with only 42% of that protein being water soluble. Then, CDS was applied as a nutrient supplement for simultaneous production of nisin and lactic acid by Lactococcus lactis subsp. lactis (ATCC 11454). Although CDS was able to support bacteria growth and nisin production, a strong inhibition was observed when CDS was overdosed. This may be caused by the existence of the major ethanol fermentation byproducts, especially lactate and acetate, in CDS. In the final step, the CDS based medium composition for nisin and lactic acid production was optimized using response surface methodology.

  4. Insecticide Resistance and Metabolic Mechanisms Involved in Larval and Adult Stages of Aedes aegypti Insecticide-Resistant Reference Strains from Cuba.

    Science.gov (United States)

    Bisset, Juan Andrés; Rodríguez, María Magdalena; French, Leydis; Severson, David W; Gutiérrez, Gladys; Hurtado, Daymi; Fuentes, Ilario

    2014-12-01

    Studies were conducted to compare levels of insecticide resistance and to determine the metabolic resistance mechanisms in larval and adult stages of Aedes aegypti from Cuba. Three insecticide-resistant reference strains of Ae. aegypti from Cuba were examined. These strains were derived from a Santiago de Cuba strain isolated in 1997; it was previously subjected to a strong selection for resistance to temephos (SAN-F6), deltamethrin (SAN-F12), and propoxur (SAN-F13) and routinely maintained in the laboratory under selection pressure up to the present time, when the study was carried out. In addition, an insecticide-susceptible strain was used for comparison. The insecticide resistance in larvae and adults was determined using standard World Health Organization methodologies. Insecticide resistance mechanisms were determined by biochemical assays. The esterases (α EST and β EST) and mixed function oxidase (MFO) activities were significantly higher in adults than in the larvae of the three resistant strains studied. The association of resistance level with the biochemical mechanism for each insecticide was established for each stage. The observed differences between larval and adult stages of Ae. aegypti in their levels of insecticide resistance and the biochemical mechanisms involved should be included as part of monitoring and surveillance activities in Ae. aegypti vector control programs.

  5. Thermodynamic secrets of multidrug resistance: A new take on transport mechanisms of secondary active antiporters.

    Science.gov (United States)

    Zhang, Xuejun C; Liu, Min; Lu, Guangyuan; Heng, Jie

    2018-03-01

    Multidrug resistance (MDR) presents a growing challenge to global public health. Drug extrusion transporters play a critical part in MDR; thus, their mechanisms of substrate recognition are being studied in great detail. In this work, we review common structural features of key transporters involved in MDR. Based on our membrane potential-driving hypothesis, we propose a general energy-coupling mechanism for secondary-active antiporters. This putative mechanism provides a common framework for understanding poly-specificity of most-if not all-MDR transporters. © 2017 The Protein Society.

  6. Cancer resistance in the blind mole rat is mediated by concerted necrotic cell death mechanism

    Science.gov (United States)

    Gorbunova, Vera; Hine, Christopher; Tian, Xiao; Ablaeva, Julia; Gudkov, Andrei V.; Nevo, Eviatar; Seluanov, Andrei

    2012-01-01

    Blind mole rats Spalax (BMR) are small subterranean rodents common in the Middle East. BMR is distinguished by its adaptations to life underground, remarkable longevity (with a maximum documented lifespan of 21 y), and resistance to cancer. Spontaneous tumors have never been observed in spalacids. To understand the mechanisms responsible for this resistance, we examined the growth of BMR fibroblasts in vitro of the species Spalax judaei and Spalax golani. BMR cells proliferated actively for 7–20 population doublings, after which the cells began secreting IFN-β, and the cultures underwent massive necrotic cell death within 3 d. The necrotic cell death phenomenon was independent of culture conditions or telomere shortening. Interestingly, this cell behavior was distinct from that observed in another long-lived and cancer-resistant African mole rat, Heterocephalus glaber, the naked mole rat in which cells display hypersensitivity to contact inhibition. Sequestration of p53 and Rb proteins using SV40 large T antigen completely rescued necrotic cell death. Our results suggest that cancer resistance of BMR is conferred by massive necrotic response to overproliferation mediated by p53 and Rb pathways, and triggered by the release of IFN-β. Thus, we have identified a unique mechanism that contributes to cancer resistance of this subterranean mammal extremely adapted to life underground. PMID:23129611

  7. Molecular Gymnastics: Mechanisms of HIV-1 Resistance to CCR5 Antagonists and Impact on Virus Phenotypes.

    Science.gov (United States)

    Roche, Michael; Borm, Katharina; Flynn, Jacqueline K; Lewin, Sharon R; Churchill, Melissa J; Gorry, Paul R

    2016-01-01

    Human immunodeficiency virus type 1 (HIV-1) enters host cells through the binding of its envelope glycoproteins (Env) to the host cell receptor CD4 and then subsequent binding to a chemokine coreceptor, either CCR5 or CXCR4. CCR5 antagonists are a relatively recent class addition to the armamentarium of anti-HIV-1 drugs. These compounds act by binding to a hydrophobic pocket formed by the transmembrane helices of CCR5 and altering the conformation of the extracellular domains, such that they are no longer recognized by Env. Maraviroc is the first drug within this class to be licenced for use in HIV-1 therapy regimens. HIV resistance to CCR5 antagonists occurs either through outgrowth of pre-existing CXCR4-using viruses, or through acquisition of the ability of CCR5-using HIV-1 to use the antagonist bound form of CCR5. In the latter scenario, the mechanism underlying resistance is through complex alterations in the way that resistant Envs engage CCR5. These significant changes are unlikely to occur without consequence to the viral entry phenotype and may also open up new avenues to target CCR5 antagonist resistant viruses. This review discusses the mechanism of action of CCR5 antagonists, how HIV resistance to CCR5 antagonists occurs, and the subsequent effects on Env function.

  8. Insertion torque versus mechanical resistance of mini- implants inserted in different cortical thickness

    Directory of Open Access Journals (Sweden)

    Renata de Faria Santos

    2014-06-01

    Full Text Available OBJECTIVE: This study aimed to measure insertion torque, tip mechanical resistance to fracture and transmucosal neck of mini-implants (MI (Conexão Sistemas de PróteseT, as well as to analyze surface morphology. METHODS: Mechanical tests were carried out to measure the insertion torque of MIs in different cortical thicknesses, and tip mechanical resistance to fracture as well as transmucosal neck of MIs. Surface morphology was assessed by scanning electron microscopy (SEM before and after the mechanical tests. RESULTS: Values of mechanical resistance to fracture (22.14 N.cm and 54.95 N.cm were higher and statistically different (P 0.05 to torsional fracture in the tip of MI (22.14 N.cm when 3 mm cortical thickness (16.11 N.cm and dense bone (23.95 N.cm were used. Torsional fracture of the transmucosal neck (54.95 N.cm was higher and statistically different (P < 0.05 from insertion torsional strength in all tested situations. SEM analysis showed that the MIs had the same smooth surface when received from the manufacturer and after the mechanical tests were performed. Additionally, no significant marks resulting from the manufacturing process were observed. CONCLUSION: All mini-implants tested presented adequate surface morphology. The resistance of mini-implants to fracture safely allows placement in 1 and 2-mm cortical thickness. However, in 3-mm cortical thickness and dense bones, pre-drilling with a bur is recommended before insertion.

  9. A Molecular Modeling Study of the Hydroxyflutamide Resistance Mechanism Induced by Androgen Receptor Mutations

    Directory of Open Access Journals (Sweden)

    Hong-Li Liu

    2017-08-01

    Full Text Available Hydroxyflutamide (HF, an active metabolite of the first generation antiandrogen flutamide, was used in clinic to treat prostate cancer targeting androgen receptor (AR. However, a drug resistance problem appears after about one year’s treatment. AR T877A is the first mutation that was found to cause a resistance problem. Then W741C_T877A and F876L_T877A mutations were also reported to cause resistance to HF, while W741C and F876L single mutations cannot. In this study, molecular dynamics (MD simulations combined with the molecular mechanics generalized Born surface area (MM-GBSA method have been carried out to analyze the interaction mechanism between HF and wild-type (WT/mutant ARs. The obtained results indicate that AR helix 12 (H12 plays a pivotal role in the resistance of HF. It can affect the coactivator binding site at the activation function 2 domain (AF2, surrounded by H3, H4, and H12. When H12 closes to the AR ligand-binding domain (LBD like a lid, the coactivator binding site can be formed to promote transcription. However, once H12 is opened to expose LBD, the coactivator binding site will be distorted, leading to invalid transcription. Moreover, per-residue free energy decomposition analyses indicate that N705, T877, and M895 are vital residues in the agonist/antagonist mechanism of HF.

  10. 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

  11. Overcoming Antimicrobial Resistance in Bacteria Using Bioactive Magnetic Nanoparticles and Pulsed Electromagnetic Fields

    Directory of Open Access Journals (Sweden)

    Vitalij Novickij

    2018-01-01

    Full Text Available Nisin is a known bacteriocin, which exhibits a wide spectrum of antimicrobial activity, while commonly being inefficient against Gram-negative bacteria. In this work, we present a proof of concept of novel antimicrobial methodology using targeted magnetic nisin-loaded nano-carriers [iron oxide nanoparticles (NPs (11–13 nm capped with citric, ascorbic, and gallic acids], which are activated by high pulsed electric and electromagnetic fields allowing to overcome the nisin-resistance of bacteria. As a cell model the Gram-positive bacteria Bacillus subtilis and Gram-negative Escherichia coli were used. We have applied 10 and 30 kV cm-1 electric field pulses (100 μs × 8 separately and in combination with two pulsed magnetic field protocols: (1 high dB/dt 3.3 T × 50 and (2 10 mT, 100 kHz, 2 min protocol to induce additional permeabilization and local magnetic hyperthermia. We have shown that the high dB/dt pulsed magnetic fields increase the antimicrobial efficiency of nisin NPs similar to electroporation or magnetic hyperthermia methods and a synergistic treatment is also possible. The results of our work are promising for the development of new methods for treatment of the drug-resistant foodborne pathogens to minimize the risks of invasive infections.

  12. Mechanism by which arylamineN-acetyltransferase 1 ablation causes insulin resistance in mice.

    Science.gov (United States)

    Camporez, João Paulo; Wang, Yongliang; Faarkrog, Kasper; Chukijrungroat, Natsasi; Petersen, Kitt Falk; Shulman, Gerald I

    2017-12-26

    A single-nucleotide polymorphism in the human arylamine N -acetyltransferase 2 (Nat2) gene has recently been identified as associated with insulin resistance in humans. To understand the cellular and molecular mechanisms by which alterations in Nat2 activity might cause insulin resistance, we examined murine ortholog Nat1 knockout (KO) mice. Nat1 KO mice manifested whole-body insulin resistance, which could be attributed to reduced muscle, liver, and adipose tissue insulin sensitivity. Hepatic and muscle insulin resistance were associated with marked increases in both liver and muscle triglyceride (TAG) and diacylglycerol (DAG) content, which was associated with increased PKCε activation in liver and increased PKCθ activation in skeletal muscle. Nat1 KO mice also displayed reduced whole-body energy expenditure and reduced mitochondrial oxygen consumption in white adipose tissue, brown adipose tissue, and hepatocytes. Taken together, these studies demonstrate that Nat1 deletion promotes reduced mitochondrial activity and is associated with ectopic lipid-induced insulin resistance. These results provide a potential genetic link among mitochondrial dysfunction with increased ectopic lipid deposition, insulin resistance, and type 2 diabetes. Copyright © 2017 the Author(s). Published by PNAS.

  13. Will the Amaranthus tuberculatus Resistance Mechanism to PPO-Inhibiting Herbicides Evolve in Other Amaranthus Species?

    Directory of Open Access Journals (Sweden)

    Chance W. Riggins

    2012-01-01

    Full Text Available Resistance to herbicides that inhibit protoporphyrinogen oxidase (PPO has been slow to evolve and, to date, is confirmed for only four weed species. Two of these species are members of the genus Amaranthus L. Previous research has demonstrated that PPO-inhibitor resistance in A. tuberculatus (Moq. Sauer, the first weed to have evolved this type of resistance, involves a unique codon deletion in the PPX2 gene. Our hypothesis is that A. tuberculatus may have been predisposed to evolving this resistance mechanism due to the presence of a repetitive motif at the mutation site and that lack of this motif in other amaranth species is why PPO-inhibitor resistance has not become more common despite strong herbicide selection pressure. Here we investigate inter- and intraspecific variability of the PPX2 gene—specifically exon 9, which includes the mutation site—in ten amaranth species via sequencing and a PCR-RFLP assay. Few polymorphisms were observed in this region of the gene, and intraspecific variation was observed only in A. quitensis. However, sequencing revealed two distinct repeat patterns encompassing the mutation site. Most notably, A. palmeri S. Watson possesses the same repetitive motif found in A. tuberculatus. We thus predict that A. palmeri will evolve resistance to PPO inhibitors via the same PPX2 codon deletion that evolved in A. tuberculatus.

  14. Numerical simulation of high-temperature thermal contact resistance and its reduction mechanism

    Science.gov (United States)

    Zhang, Jing

    2018-01-01

    High-temperature thermal contact resistance (TCR) plays an important role in heat-pipe-cooled thermal protection structures due to the existence of contact interface between the embedded heat pipe and the heat resistive structure, and the reduction mechanism of thermal contact resistance is of special interests in the design of such structures. The present paper proposed a finite element model of the high-temperature thermal contact resistance based on the multi-point contact model with the consideration of temperature-dependent material properties, heat radiation through the cavities at the interface and the effect of thermal interface material (TIM), and the geometry parameters of the finite element model are determined by simple surface roughness test and experimental data fitting. The experimental results of high-temperature thermal contact resistance between superalloy GH600 and C/C composite material are employed to validate the present finite element model. The effect of the crucial parameters on the thermal contact resistance with and without TIM are also investigated with the proposed finite element model. PMID:29547651

  15. Testing the permeability and corrosion resistance of micro-mechanically interlocked joints

    DEFF Research Database (Denmark)

    Byskov-Nielsen, Jeppe; Holm, Allan Hjarbæk; Højsholt, Rune

    2011-01-01

    Micro-mechanical interlocking (MMI) can be applied to create new and interesting composite materials. We have employed laser structuring to achieve MMI between stainless steel and plastic with extremely high joint strength. However, the water permeability and corrosion resistance of the joint must...... be taken in order not to degrade the corrosion resistance of the sample to an unacceptable level....... is conducted. The permeability seems to be consistent with the Hagen–Poiseuille equation independent of the laser structuring technique and is orders of magnitudes larger than the diffusion rate through the plastic. Two different types of corrosion tests have been undertaken, and we show that care must...

  16. BIOCHEMICAL MECHANISMS OF RESISTANCE TO p-NITROCHLOROBENZENE OF KARST CAVES MICROORGANISMS.

    Science.gov (United States)

    Suslova, O S; Rokitko, P V; Bondar, K M; Golubenko, O O; Tashyrev, A B

    2015-01-01

    The biochemical mechanisms of resistance to persistent organic xenobiotic p-nitrochlorobenzene (NCB) of bacterial strains isolated from two cave clays ecosystems-Mushkarova Yama (Podolia, Ukraine) and Kuybyshevskaya (Western Caucasus, Abkhazia) have been established It has been determined that chemoorganotrophic karst caves strains could interact with NCB and transform it reducing the nitro group withformation of p-chloroaniline (ClA) followed by further destruction of NCB aromatic ring. This explained high resistance of caves strains to NCB. The studied strains could potentially be used in wastewater treatment from nitrochloraromatic compounds.

  17. Change from lung adenocarcinoma to small cell lung cancer as a mechanism of resistance to afatinib.

    Science.gov (United States)

    Manca, Paolo; Russano, Marco; Pantano, Francesco; Tonini, Giuseppe; Santini, Daniele

    2017-08-29

    We report the case of a patient affected by advanced EGFR mutation-positive lung who experienced resistance to therapy during treatment with Afatinib through the occurrence of a switch of tumor histotype to small cell lung cancer (SCLC) with features of a G3 neuroendocrine carcinoma. Unexpectedly, the switch to SCLC histotype occurred in the only site not responsive to afatinib and subsequently the most responsive to chemotherapy. Our case shows that occurrence of switch to SCLC is a possible mechanism of resistance during treatment with Afatinib.

  18. Study on the mechanism of wheat mutants resistance to bi-polaris sorokiniana

    International Nuclear Information System (INIS)

    Sun Guangzu; Wang Guangjin; Tang Fenglan; Liu Lijun; Li Zhongjie

    1992-01-01

    The activities and band number of peroxidase (POD), superoxide dismutase (SOD) and phenylalanine aminolyase (PAL) in plant tissue have been studied after treatment with phytotoxin produced from Bi polaris sorokiniana. The results showed that the activity and band number of these enzymes have been changed markedly. The change in degree of activity for mutants was more than that of the parent, and coincident with the ability of resistance to disease. The authors considered that the toxin tolerance ability and inducibility of SOD and POD by toxin might be one of resistance mechanism of wheat mutant against Bipolaris sorokiniana

  19. Biochemical mechanisms of resistance to p-nitrochlorobenzene of karst caves microorganisms

    Directory of Open Access Journals (Sweden)

    O. S. Suslova

    2015-08-01

    Full Text Available The biochemical mechanisms of resistance to persistent organic xenobiotic p-nitrochlorobenzene (NCB of bacterial strains isolated from two cave clays ecosystems – Mushkarova Yama (Podolia, Ukraine and Kuybyshevskaya (Western Caucasus, Abkhazia have been established. It has been determined that chemoorganotrophic karst caves strains could interact with NCB and transform it reducing the nitro group with formation of p-chloroaniline (ClA followed by further destruction of NCB aromatic ring. This explained high resistance of caves strains to NCB. The studied strains could potentially be used in wastewater treatment from nitrochloraromatic compounds.

  20. Alkali-Resistant Mechanism of a Hollandite DeNOx Catalyst.

    Science.gov (United States)

    Hu, Pingping; Huang, Zhiwei; Gu, Xiao; Xu, Fei; Gao, Jiayi; Wang, Yue; Chen, Yaxin; Tang, Xingfu

    2015-06-02

    A thorough understanding of the deactivation mechanism by alkalis is of great importance for rationally designing improved alkali-resistant deNOx catalysts, but a traditional ion-exchange mechanism cannot often accurately describe the nature of the deactivation, thus hampering the development of superior catalysts. Here, we establish a new exchange-coordination mechanism on the basis of the exhaustive study on the strong alkali resistance of a hollandite manganese oxide (HMO) catalyst. A combination of isothermal adsorption measurements of ammonia with X-ray absorption near-edge structure spectra and X-ray photoelectron spectra reveals that alkali metal ions first react with protons from Brønsted acid sites of HMO via the ion exchange. Synchrotron X-ray diffraction patterns and extended X-ray absorption fine structure spectra coupled with theoretical calculations demonstrate that the exchanged alkali metal ions are subsequently stabilized at size-suitable cavities in the HMO pores via a coordination model with an energy savings. This exchange-coordination mechanism not only gives a wholly convincing explanation for the intrinsic nature of the deactivation of the reported catalysts by alkalis but also provides a strategy for rationally designing improved alkali-resistant deNOx catalysts in general.

  1. The use of high-throughput sequencing to investigate an outbreak of glycopeptide-resistant Enterococcus faecium with a novel quinupristin-dalfopristin resistance mechanism.

    Science.gov (United States)

    Shaw, Timothy D; Fairley, D J; Schneiders, T; Pathiraja, M; Hill, R L R; Werner, G; Elborn, J S; McMullan, R

    2018-02-24

    High-throughput sequencing (HTS) has successfully identified novel resistance genes in enterococci and determined clonal relatedness in outbreak analysis. We report the use of HTS to investigate two concurrent outbreaks of glycopeptide-resistant Enterococcus faecium (GRE) with an uncharacterised resistance mechanism to quinupristin-dalfopristin (QD). Seven QD-resistant and five QD-susceptible GRE isolates from a two-centre outbreak were studied. HTS was performed to identify genes or predicted proteins that were associated with the QD-resistant phenotype. MLST and SNP typing on HTS data was used to determine clonal relatedness. Comparative genomic analysis confirmed this GRE outbreak involved two distinct clones (ST80 and ST192). HTS confirmed the absence of known QD resistance genes, suggesting a novel mechanism was conferring resistance. Genomic analysis identified two significant genetic determinants with explanatory power for the high level of QD resistance in the ST80 QD-resistant clone: an additional 56aa leader sequence at the N-terminus of the lsaE gene and a transposon containing seven genes encoding proteins with possible drug or drug-target modification activities. However, HTS was unable to conclusively determine the QD resistance mechanism and did not reveal any genetic basis for QD resistance in the ST192 clone. This study highlights the usefulness of HTS in deciphering the degree of relatedness in two concurrent GRE outbreaks. Although HTS was able to reveal some genetic candidates for uncharacterised QD resistance, this study demonstrates the limitations of HTS as a tool for identifying putative determinants of resistance to QD.

  2. Thiamethoxam resistance selected in the western flower thrips Frankliniella occidentalis (Thysanoptera: Thripidae): cross-resistance patterns, possible biochemical mechanisms and fitness costs analysis.

    Science.gov (United States)

    Gao, Cong-Fen; Ma, Shao-Zhi; Shan, Cai-Hui; Wu, Shun-Fan

    2014-09-01

    The western flower thrips (WFT) Frankliniella occidentalis (Pergande) (Thysanoptera: Thripidae), an important pest of various crops in the world, has invaded China since 2003. To understand the risks and to determine possible mechanisms of resistance to thiamethoxam in WFT, a resistant strain was selected under the laboratory conditions. Cross-resistance and the possible biochemical resistance mechanisms were investigated in this study. A 15.1-fold thiamethoxam-resistant WFT strain (TH-R) was established after selection for 55 generations. Compared with the susceptible strain (TH-S), the selected TH-R strain showed extremely high level cross-resistance to imidaclothiz (392.1-fold) and low level cross-resistance to dinotefuran (5.7-fold), acetamiprid (2.9-fold) and emamectin benzoate (2.1-fold), respectively. No cross-resistance to other fourteen insecticides was detected. Synergism tests showed that piperonyl butoxide (PBO) and triphenyl phosphate (TPP) produced a high synergism of thiamethoxam effects in the TH-R strain (2.6- and 2.6-fold respectively). However, diethyl maleate (DEM) did not act synergistically with thiamethoxam. Biochemical assays showed that mixed function oxidase (MFO) activities and carboxylesterase (CarE) activity of the TH-R strain were 2.8- and 1.5-fold higher than that of the TH-S strain, respectively. When compared with the TH-S strain, the TH-R strain had a relative fitness of 0.64. The results show that WFT develops resistance to thiamethoxam after continuous application and thiamethoxam resistance had considerable fitness costs in the WFT. It appears that enhanced metabolism mediated by cytochrome P450 monooxygenases and CarE was a major mechanism for thiamethoxam resistance in the WFT. The use of cross-resistance insecticides, including imidaclothiz and dinotefuran, should be avoided for sustainable resistance management. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Effect of liposome-encapsulated nisin and bacteriocin-like substance P34 on Listeria monocytogenes growth in Minas frescal cheese.

    Science.gov (United States)

    Malheiros, Patrícia da Silva; Sant'Anna, Voltaire; Barbosa, Matheus de Souza; Brandelli, Adriano; Franco, Bernadette Dora Gombossy de Melo

    2012-06-01

    The efficacy of liposome-encapsulated nisin and bacteriocin-like substance (BLS) P34 to control growth of Listeria monocytogenes in Minas frescal cheese was investigated. Nisin and BLS P34 were encapsulated in partially purified soybean phosphatidylcholine (PC-1) and PC-1-cholesterol (7:3) liposomes. PC-1 nanovesicles were previously characterized. PC-1-cholesterol encapsulated nisin and BLS P34 presented, respectively, 218 nm and 158 nm diameters, zeta potential of -64 mV and -53 mV, and entrapment efficiency of 88.9% and 100%. All treatments reduced the population of L. monocytogenes compared to the control during 21 days of storage of Minas frescal cheese at 7°C. However, nisin and BLS P34 encapsulated in PC-1-cholesterol liposomes were less efficient in controlling L. monocytogenes growth in comparison with free and PC-1 liposome-encapsulated bacteriocins. The highest inhibitory effect was observed for nisin and BLS P34 encapsulated in PC-1 liposomes after 10 days of storage of the product. The encapsulation of bacteriocins in liposomes of partially purified soybean phosphatidylcholine may be a promising technology for the control of foodborne pathogens in cheeses. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Towards mechanisms-guided resistivity-based monitoring of damage evolution in laminated composites

    KAUST Repository

    Lubineau, Gilles

    2013-04-05

    A convenient health monitoring technique for detecting degradation in laminated composite is to monitor the change of electrical resistance along multiple conduction paths within the structure. Yet, the relations between the global modification of resistivity and the exact underlying damage map is still unclear that makes diffcult to interpret these nondestructive-testing results. The challenge is then to be able to reconstruct from these global observation the underlying damage map. This is even more diffcult due to the numerous underlying damage mechanisms that can take place either at the inter laminar of intra laminar level. This paper intends to provide some preliminary insights about strategies to recover the damage state based only on global measurements. We focus here on transverse cracking detection. We introduce the homogenization process that defines at the meso scale an equivalent homogeneous ply that is energetically equivalent to the cracked one. This can be used as a first tool to reconstruct damage maps based on global resistivity measurements.

  5. Control mechanisms of mutability: Studies on the (radiation-resistant) mutant rar-2 of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Rudolph, P.

    1981-01-01

    The author attempts a quantitative description of the resistance factor of the 2nd chromosome (rar-2) on the mutation rate after irradiation, an explanation of the mechanism of action via an analysis of induced numerical aberration, and an analysis of the genetic position of this factor and its delimination with the aid of phenotypically visible markers. A comparison of the two strains ROeI 0 and ROeI 40 was to help to investigate possible modifications of the resistance factor in the strain ROeI 40 , obtained by further selection from ROeI 0 . There was no difference between the two strains as far as the effects of the resistance factor rar-2 were concerned. (orig./MG) [de

  6. Proteomic Analysis Reveals Resistance Mechanism Against Chlorpyrifos in Frankliniella occidentalis (Thysanoptera: Thripidae).

    Science.gov (United States)

    Yan, Dan-Kan; Hu, Min; Tang, Yun-Xia; Fan, Jia-Qin

    2015-08-01

    The western flower thrips is an economically important worldwide pest of many crops, and chlorpyrifos has been used to control western flower thrips for many years. To develop a better resistance-management strategy, a chlorpyrifos-resistant strain of western flower thrips (WFT-chl) was selected in the laboratory. More than 39-fold resistance was achieved after selected by chlorpyrifos for 19 generations in comparison with the susceptible strain (WFT-S). Proteome of western flower thrips (WFT-S and WFT-chl) was investigated using a quantitative proteomics approach with isobaric tag for relative and absolute quantification technique and liquid chromatography-tandem mass spectrometry technologies. According to the functional analysis, 773 proteins identified were grouped into 10 categories of molecular functions and 706 proteins were presented in 213 kinds of pathways. Comparing the proteome of WFT-chl with that of WFT-S, a total of eight proteins were found up-regulated and three down-regulated. The results from functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that the differentially expressed protein functions in binding, catalyzing, transporting, and enzyme regulation were most important in resistance development. A list of proteins functioning in biological processes of metabolism, biological regulation, and response to stimulus was found in WFT-chl, suggesting that they are possibly the major components of the resistance mechanism to chlorpyrifos in western flower thrips. Notably, several novel potential resistance-related proteins were identified such as ribosomal protein, Vg (vitellogenin), and MACT (muscle actin), which can be used to improve our understanding of the resistance mechanisms in western flower thrips. This study provided the first comprehensive view of the complicated resistance mechanism employed by WFT-S and WFT-chl through the isobaric tag for relative and absolute quantification coupled

  7. The effect of carbon content on mechanical properties, failure and corrosion resistance of deposited chromium metal

    Directory of Open Access Journals (Sweden)

    Леонід Кімович Лещинськiй

    2017-06-01

    Full Text Available It has been shown that if choosing a metal composition for surfacing rolls and rollers of continuous casting machines, both the carbon impact on the mechanical and functional properties and the critical values of the chromium concentration, which determine the corrosion resistance of the metal with regard to electrochemical corrosion theory, should be considered as well. The paper studied the effect of chromium and carbon steel the X5-X12 type on the structure, technological strength, mechanical properties, fracturing resistance and corrosion resistance of the weld metal. The composition of chromium tool steels (deposited metal (X5-used for the rolls of hot rolling mills and (X12-used for continuous casting machines rollers correspond to these values. The impact of carbon on the properties of the deposited metal containing chromium was considered by comparing the data for both types of the deposited metal. It was found that for both types of the deposited metal (X5 and X12, the limiting value of the carbon content, providing an optimal combination of strength, ductility, failure resistance is the same. If the carbon content is more than the limiting value – (0,25% the technological strength and failure resistance of the deposited metal significantly reduce. With increasing carbon content from 0,18 to 0,25% the martensite structure has a mixed morphology – lath and plate. The strength and toughness of the deposited metal grow. Of particular interest is simultaneous increase in the specific work of failure resulted from crack inhibition at the boundary with far less solid and more ductile ferrite. As for the 5% chromium metal, the X12 type composition with 0,25% C, is borderline. With a further increase in the carbon content of the metal both ductility and failure resistance sharply decrease and with 0,40% C the growth rate of fatigue crack increases by almost 1,5 times

  8. Taxane resistance in breast cancer: mechanisms, predictive biomarkers and circumvention strategies.

    Science.gov (United States)

    Murray, S; Briasoulis, E; Linardou, H; Bafaloukos, D; Papadimitriou, C

    2012-11-01

    Taxanes are established in the treatment of metastatic breast cancer (MBC) and early breast cancer (EBC) as potent chemotherapy agents. However, their therapeutic usefulness is limited by de-novo refractoriness or acquired resistance, which are common drawbacks to most anti-cancer cytotoxics. Considering that the taxanes will remain principle chemotherapeutic agents for the treatment of breast cancer, we reviewed known mechanisms of resistance in with an outlook of optimizing their clinical use. We searched the PubMed and MEDLINE databases for articles (from inception through to 9th January 2012; last search 10/01/2012) and journals known to publish information relevant to taxane chemotherapy. We imposed no language restrictions. Search terms included: cancer, breast cancer, response, resistance, taxane, paclitaxel, docetaxel, taxol. Due to the possibility of alternative mechanisms of resistance all combination chemotherapy treated data sets were removed from our overview. Over-expression of the MDR-1 gene product Pgp was extensively studied in vitro in association with taxane resistance, but data are conflicting. Similarly, the target components microtubules, which are thought to mediate refractoriness through alterations of the expression pattern of tubulins or microtubule associated proteins and the expression of alternative tubulin isoforms, failed to confirm such associations. Little consensus has been generated for reported associations between taxane-sensitivity and mutated p53, or taxane-resistance and overexpression of Bcl-2, Bcl-xL or NFkB. In contrary sufficient in vitro data support an association of spindle assembly checkpoint (SAC) defects with resistance. Clinical data have been limited and inconsistent, which relate to the variety of methods used, lack of standardization of cut-offs for quantitation, differences in clinical endpoints measured and in methods of tissue collection preparation and storage, and study/patient heterogeneity. The most

  9. Use and Misuse of Antimicrobial Drugs in Poultry and Livestock: Mechanisms of Antimicrobial Resistance

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    Toni Poole* and Cynthia Sheffield

    2013-07-01

    Full Text Available Food safety begins on the farm with management practices that contribute to an abundant, safe, and affordable food supply. To attain this goal antimicrobials have been used in all stages of food animal production in the United States and elsewhere around the world at one time or another. Among food–production animals antimicrobials are used for growth promotion, disease prophylaxis or disease treatment, and are generally administered to the entire flock or herd. Over many decades bacteria have become resistant to multiple antimicrobial classes in a cumulative manner. Bacteria exhibit a number of well characterized mechanisms of resistance to antimicrobials that include: 1 modification of the antimicrobial; 2 alteration of the drug target; 3 decreased access of drug to target; and 4 implementation of an alternative metabolic pathway not affected by the drug. The mechanisms of resistance are complex and depend on the type of bacterium involved (e.g. Gram–positive or Gram–negative and the class of drug. Some bacterial species have accumulated resistance to nearly all antimicrobial classes due to a combination of intrinsic and acquired processes. This has and will continue to lead to clinical failures of antimicrobial treatment in both human and animal medicine.

  10. Mechanisms of resistance to linalool in Salmonella Senftenberg and their role in survival on basil.

    Science.gov (United States)

    Kalily, Emmanuel; Hollander, Amit; Korin, Ben; Cymerman, Itamar; Yaron, Sima

    2016-11-01

    Fresh produce contaminated with human pathogens raises vital and ecological questions about bacterial survival strategies. Such occurrence was basil harboring Salmonella enterica serovar Senftenberg that caused an outbreak in 2007. This host was unanticipated due to its production of antibacterial substances, including linalool. We show that linalool perforates bacterial membranes, resulting in increased permeability and leakage of vital molecules. It also inhibits cell motility and causes bacterial aggregation. Linalool-resistance was investigated by identification and characterization of S. Senftenberg mutants that perform altered resistance. Resistance mechanisms include selective permeability, regulated efflux/influx and chemotaxis-controlled motility. Moreover, survival of S. Senftenberg on basil leaves was substantially affected by McpL, a putative chemotaxis-related receptor, and RfaG, a component of the lipopolysaccharide production pathway, both have a role in resistance to linalool. Results reveal that adaptation to linalool occurs in nature by concurrent mechanisms. This adaption raises concerns about pathogens adaptation to new hosts including antimicrobial-compound-producing plants. © 2016 Society for Applied Microbiology and John Wiley & Sons Ltd.

  11. Characterization of Microstructure and Mechanical Properties of Resistance Spot Welded DP600 Steel

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    Ali Ramazani

    2015-09-01

    Full Text Available Resistance spot welding (RSW as a predominant welding technique used for joining steels in automotive applications needs to be studied carefully in order to improve the mechanical properties of the spot welds. The objectives of the present work are to characterize the resistance spot weldment of DP600 sheet steels. The mechanical properties of the welded joints were evaluated using tensile-shear and cross-tensile tests. The time-temperature evolution during the welding cycle was measured. The microstructures observed in different sites of the welds were correlated to thermal history recorded by thermocouples in the corresponding areas. It was found that cracks initiated in the periphery region of weld nuggets with a martensitic microstructure and a pull-out failure mode was observed. It was also concluded that tempering during RSW was the main reason for hardness decrease in HAZ.

  12. Ester-free Thiol-X Resins: New Materials with Enhanced Mechanical Behavior and Solvent Resistance.

    Science.gov (United States)

    Podgórski, Maciej; Becka, Eftalda; Chatani, Shunsuke; Claudino, Mauro; Bowman, Christopher N

    A series of thiol-Michael and radical thiol-ene network polymers were successfully prepared from ester-free as well as ester-containing monomer formulations. Polymerization reaction rates, dynamic mechanical analysis, and solvent resistance experiments were performed and compared between compositions with varied ester loading. The incorporation of ester-free alkyl thiol, vinyl sulfone and allylic monomers significantly improved the mechanical properties when compared with commercial, mercaptopropionate-based thiol-ene or thiol-Michael networks. For polymers with no hydrolytically degradable esters, glass transition temperatures (T g 's) as high as 100 °C were achieved. Importantly, solvent resistance tests demonstrated enhanced stability of ester-free formulations over PETMP-based polymers, especially in concentrated basic solutions. Kinetic analysis showed that glassy step-growth polymers are readily formed at ambient conditions with conversions reaching 80% and higher.

  13. Signaling Mechanisms Underlying Resistance Responses: What Have We Learned, and How Is It Being Applied?

    Science.gov (United States)

    Kachroo, Aardra; Vincelli, Paul; Kachroo, Pradeep

    2017-12-01

    Plants have evolved highly specific mechanisms to resist pathogens including preformed barriers and the induction of elaborate signaling pathways. Induced signaling requires recognition of the pathogen either via conserved pathogen-derived factors or specific pathogen-encoded proteins called effectors. Recognition of these factors by host encoded receptor proteins can result in the elicitation of different tiers of resistance at the site of pathogen infection. In addition, plants induce a type of systemic immunity which is effective at the whole plant level and protects against a broad spectrum of pathogens. Advances in our understanding of pathogen-recognition mechanisms, identification of the underlying molecular components, and their significant conservation across diverse plant species has enabled the development of novel strategies to combat plant diseases. This review discusses key advances in plant defense signaling that have been adapted or have the potential to be adapted for plant protection against microbial diseases.

  14. Molecular Mechanisms of Trastuzumab Resistance in HER2 Over expressing Breast Cancer

    International Nuclear Information System (INIS)

    Fiszman, G.L.; Jasnis, M.A.

    2011-01-01

    The epidermal growth factor receptor 2 (HER2) is a tyrosine kinase over expressed in nearly 20% to 25% of invasive breast cancers. Trastuzumab is a humanized monoclonal antibody that targets HER2. The majority of patients with metastatic breast cancer initially respond to trastuzumab, however, within 1 year of treatment disease progresses. Several molecular mechanisms have been described as contributing to the development of trastuzumab resistance. They could be grouped as impaired access of trastuzumab to HER2, up regulation of HER2 downstream signaling pathways, signaling of alternative pathways, and impaired immune antitumor mechanisms. However, since many of them have overlapping effects, it would be of great clinical impact to identify the principal signaling pathways involved in drug resistance. Significant efforts are being applied to find other therapeutic modalities besides trastuzumab treatment to be used alone or in combination with current modalities

  15. Exploring the molecular mechanisms of glucocorticoid receptor action from sensitivity to resistance.

    Science.gov (United States)

    Ramamoorthy, Sivapriya; Cidlowski, John A

    2013-01-01

    Glucocorticoids regulate a variety of physiological processes, and are commonly used to treat disorders of inflammation, autoimmune diseases, and cancer. Glucocorticoid action is predominantly mediated through the classic glucocorticoid receptor (GR), but sensitivity to glucocorticoids varies among individuals, and even within different tissues from the same individual. The molecular basis of this phenomenon can be partially explained through understanding the process of generating bioavailable ligand and the molecular heterogeneity of the GR. The molecular mechanisms that regulate glucocorticoid action highlight the dynamic nature of hormone signaling and provide novel insights into genomic glucocorticoid actions and glucocorticoid sensitivity. Although glucocorticoids are highly effective for therapeutic purposes, long-term and/or high-dose glucocorticoid administration often leads to reduced glucocorticoid sensitivity or resistance. Here, we summarize our current understanding of the mechanisms that modulate glucocorticoid sensitivity and resistance with a focus on GR-mediated signaling. Copyright © 2013 S. Karger AG, Basel.

  16. RNA interference as a resistance mechanism against crop parasites in Africa: a 'Trojan horse' approach.

    Science.gov (United States)

    Runo, Steven; Alakonya, Amos; Machuka, Jesse; Sinha, Neelima

    2011-02-01

    Biological crop pests cause serious economic losses. In Africa, the most prevalent parasites are insect pests, plant pathogenic root-knot nematodes, viruses and parasitic plants. African smallholder farmers struggle to overcome these parasitic constraints to agricultural production. Crop losses and the host range of these parasites have continued to increase in spite of the use of widely advocated control methods. A sustainable method to overcome biological pests in Africa would be to develop crop germplasm resistant to parasites. This is achievable using either genetic modification (GM) or a non-GM approach. However, there is a paucity of resistant genes available for introduction. Additionally, the biological processes underpinning host parasite resistance are not sufficiently well understood. The authors review a technology platform for using RNA-mediated interference (RNAi) as bioengineered resistance to important crop parasites in Africa. To achieve acquired resistance, a host crop is stably transformed with a transgene that encodes a hairpin RNA targeting essential parasitic genes. The RNAi sequence is chosen in such a way that it shares no homology with the host's genes, so it remains 'inactive' until parasitism. Upon parasitism, the RNAi sequence enters the parasite and post-transcriptional gene silencing (PTGS) mechanisms are activated, leading to the death of the parasite. Copyright © 2010 Society of Chemical Industry.

  17. Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase.

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    Jérémie Piton

    Full Text Available Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug active against multidrug-resistant tuberculosis. To understand at an atomic level the quinolone resistance mechanism, which emerges in extensively drug resistant tuberculosis, we performed combined functional, biophysical and structural studies of the two individual domains constituting the catalytic DNA gyrase reaction core, namely the Toprim and the breakage-reunion domains. This allowed us to produce a model of the catalytic reaction core in complex with DNA and a quinolone molecule, identifying original mechanistic properties of quinolone binding and clarifying the relationships between amino acid mutations and resistance phenotype of M. tuberculosis DNA gyrase. These results are compatible with our previous studies on quinolone resistance. Interestingly, the structure of the entire breakage-reunion domain revealed a new interaction, in which the Quinolone-Binding Pocket (QBP is blocked by the N-terminal helix of a symmetry-related molecule. This interaction provides useful starting points for designing peptide based inhibitors that target DNA gyrase to prevent its binding to DNA.

  18. Evaluation of the Mechanical Properties of Gray Cast Iron Using Electrical Resistivity Measurement

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    Bieroński M.

    2016-12-01

    Full Text Available In this paper an attempt to determine the relationship between the electrical resistivity and the tensile strength and hardness of cast iron of carbon equivalent in the range from 3.93% to 4.48%. Tests were performed on the gray cast iron for 12 different melts with different chemical composition. From one melt poured 6 samples. Based on the study of mechanical and electro-resistive determined variation characteristics of tensile strength, hardness and resistivity as a function of the carbon equivalent. Then, regression equations were developed as power functions describing the relationship between the resistivity of castings and their tensile strength and hardness. It was found a high level of regression equations to measuring points, particularly with regard to the relationship Rm=f(ρ. The obtained preliminary results indicate the possibility of application of the method of the resistance to rapid diagnostic casts on the production line, when we are dealing with repeatable production, in this case non variable geometry of the product for which it has been determinated before a regression equation.

  19. Bypass mechanisms of resistance to tyrosine kinase inhibition in chronic myelogenous leukaemia.

    Science.gov (United States)

    Marfe, Gabriella; Di Stefano, Carla

    2014-06-01

    Chronic myeloid leukaemia (CML) is a disease induced by the BCR-ABL oncogene. Tyrosine kinase inhibitors (TKIs) were introduced in the late 1990s and have revolutionized the management of CML. The majority of such patients can now expect to live a normal life providing they continue to comply with TKI treatment. However, in a significant proportion of cases, TKI resistance develops over time, requiring a change of therapy. Over the past few years, multiple molecular mechanisms of resistance have been identified and some common themes have emerged. One is the development of resistance mutations in the drug target that prevent the drug from effectively inhibiting the respective TK domain. The second is activation of alternative molecules that maintain the signalling of key downstream pathways despite sustained inhibition of the original drug target. In this mini-review, we summarize the concepts underlying resistance, the specific examples known to date and the challenges of applying this knowledge to develop improved therapeutic strategies to prevent or overcome resistance.

  20. Mechanism of multidrug resistance of human small cell lung cancer cell line H446/VP.

    Science.gov (United States)

    Wang, Yan-Ling; Yan, Yun-Li; Zhou, Na-Jing; Han, Shuo; Zhao, Jun-Xia; Cao, Cui-Li; Lü, Yu-Hong

    2010-11-01

    Small cell lung cancer (SCLC) is the most aggressive form of lung cancer. This study aimed to investigate the mechanism of human small cell lung cancer cell line resistance to etoposide (VP-16), H446/VP. The cell viability was measured by MTT assay. Immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting methods were used to detect the multidrug resistance gene (MDR1), bcl-2, bax and the topoisomerase II (Topo II) expressions in H446 and H446/VP cells after treated with or without VP-16. The 50% inhibition concentration (IC50) of VP-16 on H446 cells was 49 mg/L, and 836 mg/L was for H446/VP cells. The expressions of MDR1 and bcl-2 were up-regulated, while the amounts of bax and Topo II were reduced in H446/VP cells. After treated with 49 mg/L of VP-16, it showed that the drug could significantly inhibit bcl-2 and Topo II expressions, and increase bax expression in H446 cells compared with that of H446/VP cells. The H446/VP cell was stably resistant to VP-16. The decreased expression of Topo II was correlated with the H446/VP multidrug resistance. The elevated expressions of MDR1, and the altered apoptotic pathways also played an important role in VP-16 induced multidrug resistance of SCLC.

  1. Virulence factors and mechanisms of antimicrobial resistance in Shigella strains from periurban areas of Lima (Peru).

    Science.gov (United States)

    Lluque, Angela; Mosquito, Susan; Gomes, Cláudia; Riveros, Maribel; Durand, David; Tilley, Drake H; Bernal, María; Prada, Ana; Ochoa, Theresa J; Ruiz, Joaquim

    2015-01-01

    The study was aimed to describe the serotype, mechanisms of antimicrobial resistance, and virulence determinants in Shigella spp. isolated from Peruvian children. Eighty three Shigella spp. were serogrouped and serotyped being established the antibiotic susceptibility. The presence of 12 virulence factors (VF) and integrase 1 and 2, along with commonly found antibiotic resistance genes was established by PCR. S. flexneri was the most relevant serogroup (55 isolates, 66%), with serotype 2a most frequently detected (27 of 55, 49%), followed by S. boydii and S. sonnei at 12 isolates each (14%) and S. dysenteriae (four isolates, 5%). Fifty isolates (60%) were multi-drug resistant (MDR) including 100% of S. sonnei and 64% of S. flexneri. Resistance levels were high to trimethoprim-sulfamethoxazole (86%), tetracycline (74%), ampicillin (67%), and chloramphenicol (65%). Six isolates showed decreased azithromycin susceptibility. No isolate was resistant to nalidixic acid, ciprofloxacin, nitrofurantoin, or ceftriaxone. The most frequent resistance genes were sul2 (95%), tet(B) (92%), cat (80%), dfrA1 (47%), blaOXA-1like (40%), with intl1 and intl2 detected in 51 and 52% of the isolates, respectively. Thirty-one different VF profiles were observed, being the ipaH (100%), sen (77%), virA and icsA (75%) genes the most frequently found. Differences in the prevalence of VF were observed between species with S. flexneri isolates, particularly serotype 2a, possessing high numbers of VF. In conclusion, this study highlights the high heterogeneity of Shigella VF and resistance genes, and prevalence of MDR organisms within this geographic region. Copyright © 2015 Elsevier GmbH. All rights reserved.

  2. Diversity of Molecular Mechanisms Conferring Carbapenem Resistance to Pseudomonas aeruginosa Isolates from Saudi Arabia

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    Mohamed H. Al-Agamy

    2016-01-01

    Full Text Available Background. This study described various molecular and epidemiological characters determining antibiotic resistance patterns in Pseudomonas aeruginosa isolates. Methods. A total of 34 carbapenem-resistant P. aeruginosa clinical isolates were isolated from samples collected at a tertiary hospital in Riyadh, Saudi Arabia, from January to December 2011. Susceptibility testing, serotyping, molecular characterization of carbapenem resistance, and pulsed-field gel electrophoresis (PFGE were performed. Results. All isolates were resistant to ceftazidime, and more than half were highly resistant (minimum inhibitory concentration (MIC > 256 mg/L. Fifteen isolates had MIC values ≥64 mg/L for any of the carbapenems examined. Vietnamese extended-spectrum β-lactamase (VEB-1 (n=16/34 and oxacillinase (OXA-10 (n=14/34 were the most prevalent extended-spectrum β-lactamase and penicillinase, respectively. Verona imipenemase (VIM-1, VIM-2, VIM-4, VIM-11, and VIM-28 and imipenemase (IMP-7 variants were found in metallo-β-lactamase producers. A decrease in outer membrane porin gene (oprD expression was seen in nine isolates, and an increase in efflux pump gene (MexAB expression was detected in five isolates. Six serotypes (O:1, O:4, O:7, O:10, O:11, and O:15 were found among the 34 isolates. The predominant serotype was O:11 (16 isolates, followed by O:15 (nine isolates. PFGE analysis of the 34 carbapenem-resistant P. aeruginosa isolates revealed 14 different pulsotypes. Conclusions. These results revealed diverse mechanisms conferring carbapenem resistance to P. aeruginosa isolates from Saudi Arabia.

  3. Contribution of different mechanisms to the resistance to fluoroquinolones in clinical isolates of Salmonella enterica

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    Abeer Ahmed Rushdy

    Full Text Available OBJECTIVES: To study the potential factors include gene mutation, efflux pump and alteration of permeability associated with quinolone-resistance of Salmonella enterica strains isolated from patients with acute gastroenteritis and to evaluate the degree of synergistic activity of efflux pump inhibitors when combined with ciprofloxacin against resistant isolates. METHODS: Antimicrobial resistance patterns of fifty-eight Salmonella isolates were tested. Five isolates were selected to study the mechanism of resistance associated with quinolone group, including mutation in topoisomerase-encoding gene, altered cell permeability, and expression of an active efflux system. In addition, the combination between antibiotics and efflux pump inhibitors to overcome the microbial resistance was evaluated. RESULTS: Five Salmonella isolates totally resistant to all quinolones were studied. All isolates showed alterations in outer membrane proteins including disappearance of some or all of these proteins (Omp-A, Omp-C, Omp-D and Omp-F. Minimum inhibitory concentration values of ciprofloxacin were determined in the presence/absence of the efflux pump inhibitors: carbonyl cyanide m-chlorophenylhydrazone, norepinephrin and trimethoprim. Minimum inhibitory concentration values for two of the isolates were 2-4 fold lower with the addition of efflux pump inhibitors. All five Salmonella isolates were amplified for gyrA and parC genes and only two isolates were sequenced. S. Enteritidis 22 had double mutations at codon 83 and 87 in addition to three mutations at parC at codons 67, 76 and 80 whereas S. Typhimurium 57 had three mutations at codons 83, 87 and 119, but no mutations at parC. CONCLUSIONS: Efflux pump inhibitors may inhibit the major AcrAB-TolC in Salmonella efflux systems which are the major efflux pumps responsible for multidrug resistance in Gramnegative clinical isolates.

  4. Characterization of ceftazidime resistance mechanisms in clinical isolates of Burkholderia pseudomallei from Australia.

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    Derek S Sarovich

    Full Text Available Burkholderia pseudomallei is a gram-negative bacterium that causes the serious human disease, melioidosis. There is no vaccine against melioidosis and it can be fatal if not treated with a specific antibiotic regimen, which typically includes the third-generation cephalosporin, ceftazidime (CAZ. There have been several resistance mechanisms described for B. pseudomallei, of which the best described are amino acid changes that alter substrate specificity in the highly conserved class A β-lactamase, PenA. In the current study, we sequenced penA from isolates sequentially derived from two melioidosis patients with wild-type (1.5 µg/mL and, subsequently, resistant (16 or ≥256 µg/mL CAZ phenotypes. We identified two single-nucleotide polymorphisms (SNPs that directly increased CAZ hydrolysis. One SNP caused an amino acid substitution (C69Y near the active site of PenA, whereas a second novel SNP was found within the penA promoter region. In both instances, the CAZ resistance phenotype corresponded directly with the SNP genotype. Interestingly, these SNPs appeared after infection and under selection from CAZ chemotherapy. Through heterologous cloning and expression, and subsequent allelic exchange in the native bacterium, we confirmed the role of penA in generating both low-level and high-level CAZ resistance in these clinical isolates. Similar to previous studies, the amino acid substitution altered substrate specificity to other β-lactams, suggesting a potential fitness cost associated with this mutation, a finding that could be exploited to improve therapeutic outcomes in patients harboring CAZ resistant B. pseudomallei. Our study is the first to functionally characterize CAZ resistance in clinical isolates of B. pseudomallei and to provide proven and clinically relevant signatures for monitoring the development of antibiotic resistance in this important pathogen.

  5. Etiopathogenesis of Nonalcoholic Steatohepatitis: Role of Obesity, Insulin Resistance and Mechanisms of Hepatotoxicity

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    Praveen Guturu

    2012-01-01

    Full Text Available Incidence of nonalcoholic fatty liver disease is increasing with an estimated prevalence of 20–30% in developed nations. This is leading to increased incidence of chronic liver disease, cirrhosis, and hepatocellular cancer. It is critical to understand the etiology and pathogenesis of any disease to create therapeutic targets and develop new treatments. In this paper we discuss the etiology and pathogenesis of nonalcoholic steatohepatitis with special focus on obesity, role of insulin resistance, and molecular mechanisms of hepatotoxicity.

  6. Whole-genome sequencing reveals the mechanisms for evolution of streptomycin resistance in Lactobacillus plantarum.

    Science.gov (United States)

    Zhang, Fuxin; Gao, Jiayuan; Wang, Bini; Huo, Dongxue; Wang, Zhaoxia; Zhang, Jiachao; Shao, Yuyu

    2018-04-01

    In this research, we investigated the evolution of streptomycin resistance in Lactobacillus plantarum ATCC14917, which was passaged in medium containing a gradually increasing concentration of streptomycin. After 25 d, the minimum inhibitory concentration (MIC) of L. plantarum ATCC14917 had reached 131,072 µg/mL, which was 8,192-fold higher than the MIC of the original parent isolate. The highly resistant L. plantarum ATCC14917 isolate was then passaged in antibiotic-free medium to determine the stability of resistance. The MIC value of the L. plantarum ATCC14917 isolate decreased to 2,048 µg/mL after 35 d but remained constant thereafter, indicating that resistance was irreversible even in the absence of selection pressure. Whole-genome sequencing of parent isolates, control isolates, and isolates following passage was used to study the resistance mechanism of L. plantarum ATCC14917 to streptomycin and adaptation in the presence and absence of selection pressure. Five mutated genes (single nucleotide polymorphisms and structural variants) were verified in highly resistant L. plantarum ATCC14917 isolates, which were related to ribosomal protein S12, LPXTG-motif cell wall anchor domain protein, LrgA family protein, Ser/Thr phosphatase family protein, and a hypothetical protein that may correlate with resistance to streptomycin. After passage in streptomycin-free medium, only the mutant gene encoding ribosomal protein S12 remained; the other 4 mutant genes had reverted to the wild type as found in the parent isolate. Although the MIC value of L. plantarum ATCC14917 was reduced in the absence of selection pressure, it remained 128-fold higher than the MIC value of the parent isolate, indicating that ribosomal protein S12 may play an important role in streptomycin resistance. Using the mobile elements database, we demonstrated that streptomycin resistance-related genes in L. plantarum ATCC14917 were not located on mobile elements. This research offers a way of

  7. EXPERIMENTAL VERIFICATION OF THE MECHANICAL RESISTANCE OF FORENSIC MARKING BY MEANS SYNTHETIC DNA

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    Marek HÜTTER

    2017-06-01

    Full Text Available This article deals with experimental verification of resistance of forensic identification marks (microdots in combination with artificial DNA to property. It is considered mechanical abrasion from potential offender to remove or damage readability of marking and following identification. The aim of this work is to test the hypothesis that forensic marking can be completely removed by the process of mechanical abrasion without causing damages to a protected object. To fulfill this purpose it was designed and built a test equipment, where experiments were carried out to confirm or refute the above mentioned hypothesis.

  8. Alpha prime effect on mechanical properties and corrosion resistance of UR 52N+ duplex stainless steel

    International Nuclear Information System (INIS)

    Fontes, Talita Filier

    2009-01-01

    Alpha prime phase leads to decreased corrosion resistance and