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Sample records for intrinsic antibiotic resistance

  1. Antibiotic Capture by Bacterial Lipocalins Uncovers an Extracellular Mechanism of Intrinsic Antibiotic Resistance

    PubMed Central

    El-Halfawy, Omar M.; Klett, Javier; Ingram, Rebecca J.; Loutet, Slade A.; Murphy, Michael E. P.; Martín-Santamaría, Sonsoles

    2017-01-01

    ABSTRACT The potential for microbes to overcome antibiotics of different classes before they reach bacterial cells is largely unexplored. Here we show that a soluble bacterial lipocalin produced by Burkholderia cenocepacia upon exposure to sublethal antibiotic concentrations increases resistance to diverse antibiotics in vitro and in vivo. These phenotypes were recapitulated by heterologous expression in B. cenocepacia of lipocalin genes from Pseudomonas aeruginosa, Mycobacterium tuberculosis, and methicillin-resistant Staphylococcus aureus. Purified lipocalin bound different classes of bactericidal antibiotics and contributed to bacterial survival in vivo. Experimental and X-ray crystal structure-guided computational studies revealed that lipocalins counteract antibiotic action by capturing antibiotics in the extracellular space. We also demonstrated that fat-soluble vitamins prevent antibiotic capture by binding bacterial lipocalin with higher affinity than antibiotics. Therefore, bacterial lipocalins contribute to antimicrobial resistance by capturing diverse antibiotics in the extracellular space at the site of infection, which can be counteracted by known vitamins. PMID:28292982

  2. Antibiotic Capture by Bacterial Lipocalins Uncovers an Extracellular Mechanism of Intrinsic Antibiotic Resistance.

    PubMed

    El-Halfawy, Omar M; Klett, Javier; Ingram, Rebecca J; Loutet, Slade A; Murphy, Michael E P; Martín-Santamaría, Sonsoles; Valvano, Miguel A

    2017-03-14

    The potential for microbes to overcome antibiotics of different classes before they reach bacterial cells is largely unexplored. Here we show that a soluble bacterial lipocalin produced by Burkholderia cenocepacia upon exposure to sublethal antibiotic concentrations increases resistance to diverse antibiotics in vitro and in vivo These phenotypes were recapitulated by heterologous expression in B. cenocepacia of lipocalin genes from Pseudomonas aeruginosa, Mycobacterium tuberculosis, and methicillin-resistant Staphylococcus aureus Purified lipocalin bound different classes of bactericidal antibiotics and contributed to bacterial survival in vivo Experimental and X-ray crystal structure-guided computational studies revealed that lipocalins counteract antibiotic action by capturing antibiotics in the extracellular space. We also demonstrated that fat-soluble vitamins prevent antibiotic capture by binding bacterial lipocalin with higher affinity than antibiotics. Therefore, bacterial lipocalins contribute to antimicrobial resistance by capturing diverse antibiotics in the extracellular space at the site of infection, which can be counteracted by known vitamins.IMPORTANCE Current research on antibiotic action and resistance focuses on targeting essential functions within bacterial cells. We discovered a previously unrecognized mode of general bacterial antibiotic resistance operating in the extracellular space, which depends on bacterial protein molecules called lipocalins. These molecules are highly conserved in most bacteria and have the ability to capture different classes of antibiotics outside bacterial cells. We also discovered that liposoluble vitamins, such as vitamin E, overcome in vitro and in vivo antibiotic resistance mediated by bacterial lipocalins, providing an unexpected new alternative to combat resistance by using this vitamin or its derivatives as antibiotic adjuvants.

  3. Pseudomonas aeruginosa Reveals High Intrinsic Resistance to Penem Antibiotics: Penem Resistance Mechanisms and Their Interplay

    PubMed Central

    Okamoto, Kiyomi; Gotoh, Naomasa; Nishino, Takeshi

    2001-01-01

    Pseudomonas aeruginosa exhibits high intrinsic resistance to penem antibiotics such as faropenem, ritipenem, AMA3176, sulopenem, Sch29482, and Sch34343. To investigate the mechanisms contributing to penem resistance, we used the laboratory strain PAO1 to construct a series of isogenic mutants with an impaired multidrug efflux system MexAB-OprM and/or impaired chromosomal AmpC β-lactamase. The outer membrane barrier of PAO1 was partially eliminated by inducing the expression of the plasmid-encoded Escherichia coli major porin OmpF. Susceptibility tests using the mutants and the OmpF expression plasmid showed that MexAB-OprM and the outer membrane barrier, but not AmpC β-lactamase, are the main mechanisms involved in the high intrinsic penem resistance of PAO1. However, reducing the high intrinsic penem resistance of PAO1 to the same level as that of penem-susceptible gram-negative bacteria such as E. coli required the loss of either both MexAB-OprM and AmpC β-lactamase or both MexAB-OprM and the outer membrane barrier. Competition experiments for penicillin-binding proteins (PBPs) revealed that the affinity of PBP 1b and PBP 2 for faropenem were about 1.8- and 1.5-fold lower, than the respective affinity for imipenem. Loss of the outer membrane barrier, MexAB, and AmpC β-lactamase increased the susceptibility of PAO1 to almost all penems tested compared to the susceptibility of the AmpC-deficient PAO1 mutants to imipenem. Thus, it is suggested that the high intrinsic penem resistance of P. aeruginosa is generated from the interplay among the outer membrane barrier, the active efflux system, and AmpC β-lactamase but not from the lower affinity of PBPs for penems. PMID:11408209

  4. Pseudomonas aeruginosa reveals high intrinsic resistance to penem antibiotics: penem resistance mechanisms and their interplay.

    PubMed

    Okamoto, K; Gotoh, N; Nishino, T

    2001-07-01

    Pseudomonas aeruginosa exhibits high intrinsic resistance to penem antibiotics such as faropenem, ritipenem, AMA3176, sulopenem, Sch29482, and Sch34343. To investigate the mechanisms contributing to penem resistance, we used the laboratory strain PAO1 to construct a series of isogenic mutants with an impaired multidrug efflux system MexAB-OprM and/or impaired chromosomal AmpC beta-lactamase. The outer membrane barrier of PAO1 was partially eliminated by inducing the expression of the plasmid-encoded Escherichia coli major porin OmpF. Susceptibility tests using the mutants and the OmpF expression plasmid showed that MexAB-OprM and the outer membrane barrier, but not AmpC beta-lactamase, are the main mechanisms involved in the high intrinsic penem resistance of PAO1. However, reducing the high intrinsic penem resistance of PAO1 to the same level as that of penem-susceptible gram-negative bacteria such as E. coli required the loss of either both MexAB-OprM and AmpC beta-lactamase or both MexAB-OprM and the outer membrane barrier. Competition experiments for penicillin-binding proteins (PBPs) revealed that the affinity of PBP 1b and PBP 2 for faropenem were about 1.8- and 1.5-fold lower, than the respective affinity for imipenem. Loss of the outer membrane barrier, MexAB, and AmpC beta-lactamase increased the susceptibility of PAO1 to almost all penems tested compared to the susceptibility of the AmpC-deficient PAO1 mutants to imipenem. Thus, it is suggested that the high intrinsic penem resistance of P. aeruginosa is generated from the interplay among the outer membrane barrier, the active efflux system, and AmpC beta-lactamase but not from the lower affinity of PBPs for penems.

  5. Antibiotic Resistance

    MedlinePlus

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

  6. Assessment of three Resistance-Nodulation-Cell Division drug efflux transporters of Burkholderia cenocepacia in intrinsic antibiotic resistance

    PubMed Central

    2009-01-01

    Background Burkholderia cenocepacia are opportunistic Gram-negative bacteria that can cause chronic pulmonary infections in patients with cystic fibrosis. These bacteria demonstrate a high-level of intrinsic antibiotic resistance to most clinically useful antibiotics complicating treatment. We previously identified 14 genes encoding putative Resistance-Nodulation-Cell Division (RND) efflux pumps in the genome of B. cenocepacia J2315, but the contribution of these pumps to the intrinsic drug resistance of this bacterium remains unclear. Results To investigate the contribution of efflux pumps to intrinsic drug resistance of B. cenocepacia J2315, we deleted 3 operons encoding the putative RND transporters RND-1, RND-3, and RND-4 containing the genes BCAS0591-BCAS0593, BCAL1674-BCAL1676, and BCAL2822-BCAL2820. Each deletion included the genes encoding the RND transporter itself and those encoding predicted periplasmic proteins and outer membrane pores. In addition, the deletion of rnd-3 also included BCAL1672, encoding a putative TetR regulator. The B. cenocepacia rnd-3 and rnd-4 mutants demonstrated increased sensitivity to inhibitory compounds, suggesting an involvement of these proteins in drug resistance. Moreover, the rnd-3 and rnd-4 mutants demonstrated reduced accumulation of N-acyl homoserine lactones in the growth medium. In contrast, deletion of the rnd-1 operon had no detectable phenotypes under the conditions assayed. Conclusion Two of the three inactivated RND efflux pumps in B. cenocepacia J2315 contribute to the high level of intrinsic resistance of this strain to some antibiotics and other inhibitory compounds. Furthermore, these efflux systems also mediate accumulation in the growth medium of quorum sensing molecules that have been shown to contribute to infection. A systematic study of RND efflux systems in B. cenocepacia is required to provide a full picture of intrinsic antibiotic resistance in this opportunistic bacterium. PMID:19761586

  7. Antibiotic Resistance

    MedlinePlus

    ... For Consumers Consumer Information by Audience For Women Antibiotic Resistance Share Tweet Linkedin Pin it More sharing ... these products really help. To Learn More about Antibiotic Resistance Get Smart About Antibiotics (Video) Fact Sheets ...

  8. The intrinsic resistance of bacteria.

    PubMed

    Gang, Zhang; Jie, Feng

    2016-10-20

    Antibiotic resistance is often considered to be a trait acquired by previously susceptible bacteria, on the basis of which can be attributed to the horizontal acquisition of new genes or the occurrence of spontaneous mutation. In addition to acquired resistance, bacteria have a trait of intrinsic resistance to different classes of antibiotics. An intrinsic resistance gene is involved in intrinsic resistance, and its presence in bacterial strains is independent of previous antibiotic exposure and is not caused by horizontal gene transfer. Recently, interest in intrinsic resistance genes has increased, because these gene products not only may provide attractive therapeutic targets for development of novel drugs that rejuvenate the activity of existing antibiotics, and but also might predict future emergence of resistant pathogens if they become mobilized. In the present review, we summarize the conventional examples of intrinsic resistance, including the impermeability of cellular envelopes, the activity of multidrug efflux pumps or lack of drug targets. We also demonstrate that transferases and enzymes involved in basic bacterial metabolic processes confer intrinsic resistance in Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus. We present as well information on the cryptic intrinsic resistance genes that do not confer resistance to their native hosts but are capable of conferring resistance when their expression levels are increased and the activation of the cryptic genes. Finally, we discuss that intrinsic genes could be the origin of acquired resistance, especially in the genus Acinetobacter.

  9. An unusual class of anthracyclines potentiate Gram-positive antibiotics in intrinsically resistant Gram-negative bacteria

    PubMed Central

    Cox, Georgina; Koteva, Kalinka; Wright, Gerard D.

    2014-01-01

    Objectives An orthogonal approach taken towards novel antibacterial drug discovery involves the identification of small molecules that potentiate or enhance the activity of existing antibacterial agents. This study aimed to identify natural-product rifampicin adjuvants in the intrinsically resistant organism Escherichia coli. Methods E. coli BW25113 was screened against 1120 actinomycete fermentation extracts in the presence of subinhibitory (2 mg/L) concentrations of rifampicin. The active molecule exhibiting the greatest rifampicin potentiation was isolated using activity-guided methods and identified using mass and NMR spectroscopy. Susceptibility testing and biochemical assays were used to determine the mechanism of antibiotic potentiation. Results The anthracycline Antibiotic 301A1 was isolated from the fermentation broth of a strain of Streptomyces (WAC450); the molecule was shown to be highly synergistic with rifampicin (fractional inhibitory concentration index = 0.156) and moderately synergistic with linezolid (FIC index = 0.25) in both E. coli and Acinetobacter baumannii. Activity was associated with inhibition of efflux and the synergistic phenotype was lost when tested against E. coli harbouring mutations within the rpoB gene. Structure–activity relationship studies revealed that other anthracyclines do not synergize with rifampicin and removal of the sugar moiety of Antibiotic 301A1 abolishes activity. Conclusions Screening only a subsection of our natural product library identified a small-molecule antibiotic adjuvant capable of sensitizing Gram-negative bacteria to antibiotics to which they are ordinarily intrinsically resistant. This result demonstrates the great potential of this approach in expanding antibiotic effectiveness in the face of the growing challenge of resistance in Gram-negatives. PMID:24627312

  10. The role of outer membrane in Serratia marcescens intrinsic resistance to antibiotics.

    PubMed

    Sánchez, L; Ruiz, N; Leranoz, S; Viñas, M; Puig, M

    1997-09-01

    Three different porins from Serratia marcescens were described. They were named Omp1, Omp2 and Omp3 and their molecular weights were 42, 40 and 39 kDa respectively. Omp2 and Omp3 showed osmoregulation and thermoregulation in a similar way to OmpC and OmpF of Escherichia coli. Permeability coefficients of the outer membrane of this species were calculated following the Zimmermann and Rosselet method. P values were similar to those obtained in Escherichia coli, which suggests that the chromosomal beta-lactamase would play a major role in the resistance of Serratia marcescens to beta-lactam antibiotics. Both MIC values and permeabilities were modified by salycilates and acetylsalycilate. Synergism between the outer membrane and the beta-lactamase was also evaluated. When bacteria grew in the presence of a beta-lactam in the medium, the beta-lactamase accounted for most of the resistance.

  11. Molecular mechanisms of antibiotic resistance.

    PubMed

    Blair, Jessica M A; Webber, Mark A; Baylay, Alison J; Ogbolu, David O; Piddock, Laura J V

    2015-01-01

    Antibiotic-resistant bacteria that are difficult or impossible to treat are becoming increasingly common and are causing a global health crisis. Antibiotic resistance is encoded by several genes, many of which can transfer between bacteria. New resistance mechanisms are constantly being described, and new genes and vectors of transmission are identified on a regular basis. This article reviews recent advances in our understanding of the mechanisms by which bacteria are either intrinsically resistant or acquire resistance to antibiotics, including the prevention of access to drug targets, changes in the structure and protection of antibiotic targets and the direct modification or inactivation of antibiotics.

  12. Proteasome Accessory Factor C (pafC) Is a novel gene Involved in Mycobacterium Intrinsic Resistance to broad-spectrum antibiotics--Fluoroquinolones.

    PubMed

    Li, Qiming; Xie, Longxiang; Long, Quanxin; Mao, Jinxiao; Li, Hui; Zhou, Mingliang; Xie, Jianping

    2015-07-03

    Antibiotics resistance poses catastrophic threat to global public health. Novel insights into the underlying mechanisms of action will inspire better measures to control drug resistance. Fluoroquinolones are potent and widely prescribed broad-spectrum antibiotics. Bacterial protein degradation pathways represent novel druggable target for the development of new classes of antibiotics. Mycobacteria proteasome accessory factor C (pafC), a component of bacterial proteasome, is involved in fluoroquinolones resistance. PafC deletion mutants are hypersensitive to fluoroquinolones, including moxifloxacin, norfloxacin, ofloxacin, ciprofloxacin, but not to other antibiotics such as isoniazid, rifampicin, spectinomycin, chloramphenicol, capreomycin. This phenotype can be restored by complementation. The pafC mutant is hypersensitive to H2O2 exposure. The iron chelator (bipyridyl) and a hydroxyl radical scavenger (thiourea) can abolish the difference. The finding that pafC is a novel intrinsic selective resistance gene provided new evidence for the bacterial protein degradation pathway as druggable target for the development of new class of antibiotics.

  13. Resistance-resistant antibiotics.

    PubMed

    Oldfield, Eric; Feng, Xinxin

    2014-12-01

    New antibiotics are needed because drug resistance is increasing while the introduction of new antibiotics is decreasing. We discuss here six possible approaches to develop 'resistance-resistant' antibiotics. First, multitarget inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy owing to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, repurposing existing drugs can lead to combinations of multitarget therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and, in some cases, suggest that sensitivity to existing antibiotics may be restored in otherwise drug-resistant organisms.

  14. Tetracycline Antibiotics and Resistance.

    PubMed

    Grossman, Trudy H

    2016-04-01

    Tetracyclines possess many properties considered ideal for antibiotic drugs, including activity against Gram-positive and -negative pathogens, proven clinical safety, acceptable tolerability, and the availability of intravenous (IV) and oral formulations for most members of the class. As with all antibiotic classes, the antimicrobial activities of tetracyclines are subject to both class-specific and intrinsic antibiotic-resistance mechanisms. Since the discovery of the first tetracyclines more than 60 years ago, ongoing optimization of the core scaffold has produced tetracyclines in clinical use and development that are capable of thwarting many of these resistance mechanisms. New chemistry approaches have enabled the creation of synthetic derivatives with improved in vitro potency and in vivo efficacy, ensuring that the full potential of the class can be explored for use against current and emerging multidrug-resistant (MDR) pathogens, including carbapenem-resistant Enterobacteriaceae, MDR Acinetobacter species, and Pseudomonas aeruginosa.

  15. Antibiotic / Antimicrobial Resistance Glossary

    MedlinePlus

    ... National Activities Get Smart: Know When Antibiotics Work Strategies and Plans Related CDC Education Programs Global Activities Measuring Outpatient Antibiotic Prescribing Tracking Antibiotic-Resistant ...

  16. Facts about Antibiotic Resistance

    MedlinePlus

    ... National Activities Get Smart: Know When Antibiotics Work Strategies and Plans Related CDC Education Programs Global Activities Measuring Outpatient Antibiotic Prescribing Tracking Antibiotic-Resistant ...

  17. The Rcs phosphorelay is a cell envelope stress response activated by peptidoglycan stress and contributes to intrinsic antibiotic resistance.

    PubMed

    Laubacher, Mary E; Ades, Sarah E

    2008-03-01

    Gram-negative bacteria possess stress responses to maintain the integrity of the cell envelope. Stress sensors monitor outer membrane permeability, envelope protein folding, and energization of the inner membrane. The systems used by gram-negative bacteria to sense and combat stress resulting from disruption of the peptidoglycan layer are not well characterized. The peptidoglycan layer is a single molecule that completely surrounds the cell and ensures its structural integrity. During cell growth, new peptidoglycan subunits are incorporated into the peptidoglycan layer by a series of enzymes called the penicillin-binding proteins (PBPs). To explore how gram-negative bacteria respond to peptidoglycan stress, global gene expression analysis was used to identify Escherichia coli stress responses activated following inhibition of specific PBPs by the beta-lactam antibiotics amdinocillin (mecillinam) and cefsulodin. Inhibition of PBPs with different roles in peptidoglycan synthesis has different consequences for cell morphology and viability, suggesting that not all perturbations to the peptidoglycan layer generate equivalent stresses. We demonstrate that inhibition of different PBPs resulted in both shared and unique stress responses. The regulation of capsular synthesis (Rcs) phosphorelay was activated by inhibition of all PBPs tested. Furthermore, we show that activation of the Rcs phosphorelay increased survival in the presence of these antibiotics, independently of capsule synthesis. Both activation of the phosphorelay and survival required signal transduction via the outer membrane lipoprotein RcsF and the response regulator RcsB. We propose that the Rcs pathway responds to peptidoglycan damage and contributes to the intrinsic resistance of E. coli to beta-lactam antibiotics.

  18. Mechanisms of intrinsic resistance and acquired susceptibility of Pseudomonas aeruginosa isolated from cystic fibrosis patients to temocillin, a revived antibiotic

    PubMed Central

    Chalhoub, Hussein; Pletzer, Daniel; Weingart, Helge; Braun, Yvonne; Tunney, Michael M.; Elborn, J. Stuart; Rodriguez-Villalobos, Hector; Plésiat, Patrick; Kahl, Barbara C.; Denis, Olivier; Winterhalter, Mathias; Tulkens, Paul M.; Van Bambeke, Françoise

    2017-01-01

    The β-lactam antibiotic temocillin (6-α-methoxy-ticarcillin) shows stability to most extended spectrum β-lactamases, but is considered inactive against Pseudomonas aeruginosa. Mutations in the MexAB-OprM efflux system, naturally occurring in cystic fibrosis (CF) isolates, have been previously shown to reverse this intrinsic resistance. In the present study, we measured temocillin activity in a large collection (n = 333) of P. aeruginosa CF isolates. 29% of the isolates had MICs ≤ 16 mg/L (proposed clinical breakpoint for temocillin). Mutations were observed in mexA or mexB in isolates for which temocillin MIC was ≤512 mg/L (nucleotide insertions or deletions, premature termination, tandem repeat, nonstop, and missense mutations). A correlation was observed between temocillin MICs and efflux rate of N-phenyl-1-naphthylamine (MexAB-OprM fluorescent substrate) and extracellular exopolysaccharide abundance (contributing to a mucoid phenotype). OpdK or OpdF anion-specific porins expression decreased temocillin MIC by ~1 two-fold dilution only. Contrarily to the common assumption that temocillin is inactive on P. aeruginosa, we show here clinically-exploitable MICs on a non-negligible proportion of CF isolates, explained by a wide diversity of mutations in mexA and/or mexB. In a broader context, this work contributes to increase our understanding of MexAB-OprM functionality and help delineating how antibiotics interact with MexA and MexB. PMID:28091521

  19. Resistance-Resistant Antibiotics

    PubMed Central

    Oldfield, Eric; Feng, Xinxin

    2014-01-01

    New antibiotics are needed because as drug resistance is increasing, the introduction of new antibiotics is decreasing. Here, we discuss six possible approaches to develop ‘resistance-resistant’ antibiotics. First, multi-target inhibitors in which a single compound inhibits more than one target may be easier to develop than conventional combination therapies with two new drugs. Second, inhibiting multiple targets in the same metabolic pathway is expected to be an effective strategy due to synergy. Third, discovering multiple-target inhibitors should be possible by using sequential virtual screening. Fourth, re-purposing existing drugs can lead to combinations of multi-target therapeutics. Fifth, targets need not be proteins. Sixth, inhibiting virulence factor formation and boosting innate immunity may also lead to decreased susceptibility to resistance. Although it is not possible to eliminate resistance, the approaches reviewed here offer several possibilities for reducing the effects of mutations and in some cases suggest that sensitivity to existing antibiotics may be restored, in otherwise drug resistant organisms. PMID:25458541

  20. Antibiotic resistance in Chlamydiae.

    PubMed

    Sandoz, Kelsi M; Rockey, Daniel D

    2010-09-01

    There are few documented reports of antibiotic resistance in Chlamydia and no examples of natural and stable antibiotic resistance in strains collected from humans. While there are several reports of clinical isolates exhibiting resistance to antibiotics, these strains either lost their resistance phenotype in vitro, or lost viability altogether. Differences in procedures for chlamydial culture in the laboratory, low recovery rates of clinical isolates and the unknown significance of heterotypic resistance observed in culture may interfere with the recognition and interpretation of antibiotic resistance. Although antibiotic resistance has not emerged in chlamydiae pathogenic to humans, several lines of evidence suggest they are capable of expressing significant resistant phenotypes. The adept ability of chlamydiae to evolve to antibiotic resistance in vitro is demonstrated by contemporary examples of mutagenesis, recombination and genetic transformation. The isolation of tetracycline-resistant Chlamydia suis strains from pigs also emphasizes their adaptive ability to acquire antibiotic resistance genes when exposed to significant selective pressure.

  1. A diverse intrinsic antibiotic resistome from a cave bacterium

    PubMed Central

    Pawlowski, Andrew C.; Wang, Wenliang; Koteva, Kalinka; Barton, Hazel A.; McArthur, Andrew G.; Wright, Gerard D.

    2016-01-01

    Antibiotic resistance is ancient and widespread in environmental bacteria. These are therefore reservoirs of resistance elements and reflective of the natural history of antibiotics and resistance. In a previous study, we discovered that multi-drug resistance is common in bacteria isolated from Lechuguilla Cave, an underground ecosystem that has been isolated from the surface for over 4 Myr. Here we use whole-genome sequencing, functional genomics and biochemical assays to reveal the intrinsic resistome of Paenibacillus sp. LC231, a cave bacterial isolate that is resistant to most clinically used antibiotics. We systematically link resistance phenotype to genotype and in doing so, identify 18 chromosomal resistance elements, including five determinants without characterized homologues and three mechanisms not previously shown to be involved in antibiotic resistance. A resistome comparison across related surface Paenibacillus affirms the conservation of resistance over millions of years and establishes the longevity of these genes in this genus. PMID:27929110

  2. Antibiotics and Resistance: Glossary

    MedlinePlus

    ... induced by natural or human activity on the ecology and living organisms. Ecology The study of the relationships and interactions between ... antibiotics The Cost of Resistance Science of Resistance Ecology Antibiotics in Agriculture Antibacterial Agents Glossary References Web ...

  3. Antibiotic resistance in probiotic bacteria

    PubMed Central

    Gueimonde, Miguel; Sánchez, Borja; G. de los Reyes-Gavilán, Clara; Margolles, Abelardo

    2013-01-01

    Probiotics are live microorganisms which when administered in adequate amounts confer a health benefit on the host. The main probiotic bacteria are strains belonging to the genera Lactobacillus and Bifidobacterium, although other representatives, such as Bacillus or Escherichia coli strains, have also been used. Lactobacillus and Bifidobacterium are two common inhabitants of the human intestinal microbiota. Also, some species are used in food fermentation processes as starters, or as adjunct cultures in the food industry. With some exceptions, antibiotic resistance in these beneficial microbes does not constitute a safety concern in itself, when mutations or intrinsic resistance mechanisms are responsible for the resistance phenotype. In fact, some probiotic strains with intrinsic antibiotic resistance could be useful for restoring the gut microbiota after antibiotic treatment. However, specific antibiotic resistance determinants carried on mobile genetic elements, such as tetracycline resistance genes, are often detected in the typical probiotic genera, and constitute a reservoir of resistance for potential food or gut pathogens, thus representing a serious safety issue. PMID:23882264

  4. Antibiotic Resistance Questions and Answers

    MedlinePlus

    ... National Activities Get Smart: Know When Antibiotics Work Strategies and Plans Related CDC Education Programs Global Activities Measuring Outpatient Antibiotic Prescribing Tracking Antibiotic-Resistant ...

  5. Diversity within Serogroups of Rhizobium leguminosarum biovar viceae in the Palouse Region of Eastern Washington as Indicated by Plasmid Profiles, Intrinsic Antibiotic Resistance, and Topography

    PubMed Central

    Brockman, F. J.; Bezdicek, D. F.

    1989-01-01

    Serology, plasmid profiles, and intrinsic antibiotic resistance (IAR) were determined for 192 isolates of Rhizobium leguminosarum biovar viceae from nodules of peas (Pisum sativum L.) grown on the south slope and bottomland topographic positions in eastern Washington State. A total of 3 serogroups and 18 plasmid profile groups were identified. Nearly all isolates within each plasmid profile group were specific for one of the three serogroups. Cluster analysis of IAR data showed that individual clusters were dominated by one serogroup and by one or two plasmid profile groups. Plasmid profile analysis and IAR analysis grouped 72% of the isolates similarly. Most plasmid profile groups and several IAR clusters favored either the south slope or the bottomland topographic position. These findings show that certain intraserogroup strains possess a greater competitiveness for nodulation and/or possess a greater ability to survive in adjacent soil environments. Images PMID:16347814

  6. Targeting Antibiotic Resistance

    PubMed Central

    Chellat, Mathieu F.; Raguž, Luka

    2016-01-01

    Abstract Finding strategies against the development of antibiotic resistance is a major global challenge for the life sciences community and for public health. The past decades have seen a dramatic worldwide increase in human‐pathogenic bacteria that are resistant to one or multiple antibiotics. More and more infections caused by resistant microorganisms fail to respond to conventional treatment, and in some cases, even last‐resort antibiotics have lost their power. In addition, industry pipelines for the development of novel antibiotics have run dry over the past decades. A recent world health day by the World Health Organization titled “Combat drug resistance: no action today means no cure tomorrow” triggered an increase in research activity, and several promising strategies have been developed to restore treatment options against infections by resistant bacterial pathogens. PMID:27000559

  7. Antibiotic-Resistant Bacteria.

    ERIC Educational Resources Information Center

    Longenecker, Nevin E.; Oppenheimer, Dan

    1982-01-01

    A study conducted by high school advanced bacteriology students appears to confirm the hypothesis that the incremental administration of antibiotics on several species of bacteria (Escherichia coli, Staphylococcus epidermis, Bacillus sublitus, Bacillus megaterium) will allow for the development of antibiotic-resistant strains. (PEB)

  8. Pneumococcal resistance to antibiotics.

    PubMed Central

    Klugman, K P

    1990-01-01

    The geographic distribution of pneumococci resistant to one or more of the antibiotics penicillin, erythromycin, trimethoprim-sulfamethoxazole, and tetracycline appears to be expanding, and there exist foci of resistance to chloramphenicol and rifampin. Multiply resistant pneumococci are being encountered more commonly and are more often community acquired. Factors associated with infection caused by resistant pneumococci include young age, duration of hospitalization, infection with a pneumococcus of serogroup 6, 19, or 23 or serotype 14, and exposure to antibiotics to which the strain is resistant. At present, the most useful drugs for the management of resistant pneumococcal infections are cefotaxime, ceftriaxone, vancomycin, and rifampin. If the strains are susceptible, chloramphenicol may be useful as an alternative, less expensive agent. Appropriate interventions for the control of resistant pneumococcal outbreaks include investigation of the prevalence of resistant strains, isolation of patients, possible treatment of carriers, and reduction of usage of antibiotics to which the strain is resistant. The molecular mechanisms of penicillin resistance are related to the structure and function of penicillin-binding proteins, and the mechanisms of resistance to other agents involved in multiple resistance are being elucidated. Recognition is increasing of the standard screening procedure for penicillin resistance, using a 1-microgram oxacillin disk. PMID:2187594

  9. Antibiotic resistance in Burkholderia species.

    PubMed

    Rhodes, Katherine A; Schweizer, Herbert P

    2016-09-01

    The genus Burkholderia comprises metabolically diverse and adaptable Gram-negative bacteria, which thrive in often adversarial environments. A few members of the genus are prominent opportunistic pathogens. These include Burkholderia mallei and Burkholderia pseudomallei of the B. pseudomallei complex, which cause glanders and melioidosis, respectively. Burkholderia cenocepacia, Burkholderia multivorans, and Burkholderia vietnamiensis belong to the Burkholderia cepacia complex and affect mostly cystic fibrosis patients. Infections caused by these bacteria are difficult to treat because of significant antibiotic resistance. The first line of defense against antimicrobials in Burkholderia species is the outer membrane penetration barrier. Most Burkholderia contain a modified lipopolysaccharide that causes intrinsic polymyxin resistance. Contributing to reduced drug penetration are restrictive porin proteins. Efflux pumps of the resistance nodulation cell division family are major players in Burkholderia multidrug resistance. Third and fourth generation β-lactam antibiotics are seminal for treatment of Burkholderia infections, but therapeutic efficacy is compromised by expression of several β-lactamases and ceftazidime target mutations. Altered DNA gyrase and dihydrofolate reductase targets cause fluoroquinolone and trimethoprim resistance, respectively. Although antibiotic resistance hampers therapy of Burkholderia infections, the characterization of resistance mechanisms lags behind other non-enteric Gram-negative pathogens, especially ESKAPE bacteria such as Acinetobacter baumannii, Klebsiella pneumoniae and Pseudomonas aeruginosa.

  10. Mechanisms of Antibiotic Resistance

    PubMed Central

    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

  11. Predicting antibiotic resistance.

    PubMed

    Martínez, José L; Baquero, Fernando; Andersson, Dan I

    2007-12-01

    The treatment of bacterial infections is increasingly complicated because microorganisms can develop resistance to antimicrobial agents. This article discusses the information that is required to predict when antibiotic resistance is likely to emerge in a bacterial population. Indeed, the development of the conceptual and methodological tools required for this type of prediction represents an important goal for microbiological research. To this end, we propose the establishment of methodological guidelines that will allow researchers to predict the emergence of resistance to a new antibiotic before its clinical introduction.

  12. [Resistance to antibiotics].

    PubMed

    Sánchez, Jesús Silva

    2006-01-01

    Bacterial resistance to antibiotics is a major public health problem around the world causing high rates of morbi-mortality and economic problems in hospital settings. Major bacterial causing nosocomial infections are: extended-spectrum beta-lactameses (ESBL) producing enterobacteria, methicillin resistance Staphylococcus aureus, coagulase negative Staphylococcus, metallo fl-lactamases (MBL) producing Pseudomonas aeruginosa, Streptococcus pneumoniae, Enterococcus spp, Acinetobacter baumani. This last bacteria is not very often isolated in hospital settings yet, but it is multi-resistance pathogen causing high mortality. Helicobacter pylori, which is not a nosocomial pathogen but is associated to gastric diseases (from gastritis to gastric cancer). Infections prevention, to obtain an accuracy diagnostic and effective treatment, use antibiotic wisely and pathogen dissemination prevention (hand washing), are important steps to control the bacterial resistance.

  13. Antibiotic-Resistant Gonorrhea (ARG)

    MedlinePlus

    ... Twitter STD on Facebook Sexually Transmitted Diseases (STDs) Antibiotic-Resistant Gonorrhea Basic Information Recommend on Facebook Tweet ... Page Surveillance Trends and Treatment Challenges Laboratory Issues Antibiotic resistance (AR) is the ability of bacteria to ...

  14. Mission Critical: Preventing Antibiotic Resistance

    MedlinePlus

    ... Button Past Emails CDC Features Mission Critical: Preventing Antibiotic Resistance Recommend on Facebook Tweet Share Compartir Can ... spp. So, what can we do to prevent antibiotic resistance in healthcare settings? Patients, healthcare providers, healthcare ...

  15. Investigating the Antibiotic Resistance Problem.

    ERIC Educational Resources Information Center

    Lawson, Michael; Lawson, Amy L.

    1998-01-01

    Seeks to give teachers useful information on the extent of the problem of antibiotic-resistant bacteria, mechanisms bacteria use to resist antibiotics, the causes of the emergence of antibiotic-resistant organisms, and practices that can prevent or reverse this trend. Contains 19 references. (DDR)

  16. Strategies to Minimize Antibiotic Resistance

    PubMed Central

    Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee

    2013-01-01

    Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics. PMID:24036486

  17. Strategies to minimize antibiotic resistance.

    PubMed

    Lee, Chang-Ro; Cho, Ill Hwan; Jeong, Byeong Chul; Lee, Sang Hee

    2013-09-12

    Antibiotic resistance can be reduced by using antibiotics prudently based on guidelines of antimicrobial stewardship programs (ASPs) and various data such as pharmacokinetic (PK) and pharmacodynamic (PD) properties of antibiotics, diagnostic testing, antimicrobial susceptibility testing (AST), clinical response, and effects on the microbiota, as well as by new antibiotic developments. The controlled use of antibiotics in food animals is another cornerstone among efforts to reduce antibiotic resistance. All major resistance-control strategies recommend education for patients, children (e.g., through schools and day care), the public, and relevant healthcare professionals (e.g., primary-care physicians, pharmacists, and medical students) regarding unique features of bacterial infections and antibiotics, prudent antibiotic prescribing as a positive construct, and personal hygiene (e.g., handwashing). The problem of antibiotic resistance can be minimized only by concerted efforts of all members of society for ensuring the continued efficiency of antibiotics.

  18. Endless Resistance. Endless Antibiotics?

    PubMed Central

    Fisher, Jed F.; Mobashery, Shahriar

    2016-01-01

    The practice of medicine was profoundly transformed by the introduction of the antibiotics (compounds isolated from Nature) and the antibacterials (compounds prepared by synthesis) for the control of bacterial infection. As a result of the extraordinary success of these compounds over decades of time, a timeless biological activity for these compounds has been presumed. This presumption is no longer. The inexorable acquisition of resistance mechanisms by bacteria is retransforming medical practice. Credible answers to this dilemma are far better recognized than they are being implemented. In this perspective we examine (and in key respects, reiterate) the chemical and biological strategies being used to address the challenge of bacterial resistance. PMID:27746889

  19. Bacterial cheating limits antibiotic resistance

    NASA Astrophysics Data System (ADS)

    Xiao Chao, Hui; Yurtsev, Eugene; Datta, Manoshi; Artemova, Tanya; Gore, Jeff

    2012-02-01

    The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain---which does not contribute to breaking down the antibiotic---may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors.

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

    PubMed Central

    Olaitan, Abiola O.; Morand, Serge; Rolain, Jean-Marc

    2014-01-01

    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. PMID:25505462

  1. Fighting antibiotic resistance in the intensive care unit using antibiotics.

    PubMed

    Plantinga, Nienke L; Wittekamp, Bastiaan H J; van Duijn, Pleun J; Bonten, Marc J M

    2015-01-01

    Antibiotic resistance is a global and increasing problem that is not counterbalanced by the development of new therapeutic agents. The prevalence of antibiotic resistance is especially high in intensive care units with frequently reported outbreaks of multidrug-resistant organisms. In addition to classical infection prevention protocols and surveillance programs, counterintuitive interventions, such as selective decontamination with antibiotics and antibiotic rotation have been applied and investigated to control the emergence of antibiotic resistance. This review provides an overview of selective oropharyngeal and digestive tract decontamination, decolonization of methicillin-resistant Staphylococcus aureus and antibiotic rotation as strategies to modulate antibiotic resistance in the intensive care unit.

  2. Antibiotic resistant in microorganisms

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial agents are necessary for use in veterinary medicine including the production of food producing animals. Antibiotic use is indicated for the treatment of bacterial target organisms and/or disease for which the antibiotic was developed. However, an unintended consequence of antibiotic ...

  3. Molecular mechanisms of antibiotic resistance.

    PubMed

    Wright, Gerard D

    2011-04-14

    Over the past decade, resistance to antibiotics has emerged as a crisis of global proportion. Microbes resistant to many and even all clinically approved antibiotics are increasingly common and easily spread across continents. At the same time there are fewer new antibiotic drugs coming to market. We are reaching a point where we are no longer able to confidently treat a growing number of bacterial infections. The molecular mechanisms of drug resistance provide the essential knowledge on new drug development and clinical use. These mechanisms include enzyme catalyzed antibiotic modifications, bypass of antibiotic targets and active efflux of drugs from the cell. Understanding the chemical rationale and underpinnings of resistance is an essential component of our response to this clinical challenge.

  4. [Antibiotic resistance: A global crisis].

    PubMed

    Alós, Juan-Ignacio

    2015-12-01

    The introduction of antibiotics into clinical practice represented one of the most important interventions for the control of infectious diseases. Antibiotics have saved millions of lives and have also brought a revolution in medicine. However, an increasing threat has deteriorated the effectiveness of these drugs, that of bacterial resistance to antibiotics, which is defined here as the ability of bacteria to survive in antibiotic concentrations that inhibit/kill others of the same species. In this review some recent and important examples of resistance in pathogens of concern for mankind are mentioned. It is explained, according to present knowledge, the process that led to the current situation in a short time, evolutionarily speaking. It begins with the resistance genes, continues with clones and genetic elements involved in the maintenance and dissemination, and ends with other factors that contribute to its spread. Possible responses to the problem are also reviewed, with special reference to the development of new antibiotics.

  5. Antibiotic resistance: An ethical challenge.

    PubMed

    Littmann, Jasper; Buyx, Alena; Cars, Otto

    2015-10-01

    In this paper, we argue that antibiotic resistance (ABR) raises a number of ethical problems that have not yet been sufficiently addressed. We outline four areas in which ethical issues that arise in relation to ABR are particularly pressing. First, the emergence of multidrug-resistant and extensively drug-resistant infections exacerbates traditional ethical challenges of infectious disease control, such as the restriction of individual liberty for the protection of the public's health. Second, ABR raises issues of global distributive justice, both with regard to the overuse and lack of access to antibiotics. Third, the use of antibiotics in veterinary medicine raises serious concerns for animal welfare and sustainable farming practices. Finally, the diminishing effectiveness of antibiotics leads to questions about intergenerational justice and our responsibility for the wellbeing of future generations. We suggest that current policy discussions should take ethical conflicts into account and engage openly with the challenges that we outline in this paper.

  6. [Strategies to avoid antibiotic resistance].

    PubMed

    Kees, M G

    2013-03-01

    Antibiotics are used very frequently in critically ill patients as a causal and often life-saving treatment; however, the high density of use of broad spectrum antibiotics contributes to a further deterioration in resistance trends, which makes a rational prescription behavior mandatory. This particularly includes measures which lead to the reduction of antibiotic use, i.e. rigorous indications, targeted de-escalation and limited duration. For optimal efficacy of a necessary treatment the integration of pharmacokinetic and pharmacodynamic principles can be helpful.

  7. Two Small RNAs Conserved in Enterobacteriaceae Provide Intrinsic Resistance to Antibiotics Targeting the Cell Wall Biosynthesis Enzyme Glucosamine-6-Phosphate Synthase

    PubMed Central

    Khan, Muna A.; Göpel, Yvonne; Milewski, Slawomir; Görke, Boris

    2016-01-01

    Formation of glucosamine-6-phosphate (GlcN6P) by enzyme GlcN6P synthase (GlmS) represents the first step in bacterial cell envelope synthesis. In Escherichia coli, expression of glmS is controlled by small RNAs (sRNAs) GlmY and GlmZ. GlmZ activates the glmS mRNA by base-pairing. When not required, GlmZ is bound by adapter protein RapZ and recruited to cleavage by RNase E inactivating the sRNA. The homologous sRNA GlmY activates glmS indirectly. When present at high levels, GlmY sequesters RapZ by an RNA mimicry mechanism suppressing cleavage of GlmZ. The interplay of both sRNAs is believed to adjust GlmS synthesis to the needs of the cell, i.e., to achieve GlcN6P homeostasis. Bacilysin (tetaine) and Nva-FMDP are dipeptide antibiotics that impair cell envelope synthesis by inhibition of enzyme GlmS through covalent modification. However, although taken up efficiently, these antibiotics are less active against E. coli for reasons unknown so far. Here we show that the GlmY/GlmZ circuit provides resistance. Inhibition of GlmS causes GlcN6P deprivation leading to activation of GlmY and GlmZ, which in turn trigger glmS overexpression in a dosage-dependent manner. Mutation of glmY or glmZ disables this response and renders the bacteria highly susceptible to GlmS inhibitors. Thus, E. coli compensates inhibition of GlmS by increasing its synthesis through the GlmY/GlmZ pathway. This mechanism is also operative in Salmonella indicating that it is conserved in Enterobacteriaceae possessing these sRNAs. As GlmY apparently responds to GlcN6P, co-application of a non-metabolizable GlcN6P analog may prevent activation of the sRNAs and thereby increase the bactericidal activity of GlmS inhibitors against wild-type bacteria. Initial experiments using glucosamine-6-sulfate support this possibility. Thus, GlcN6P analogs might be considered for co-application with GlmS inhibitors in combined therapy to treat infections caused by pathogenic Enterobacteriaceae. PMID:27379045

  8. The multifaceted roles of antibiotics and antibiotic resistance in nature

    PubMed Central

    Sengupta, Saswati; Chattopadhyay, Madhab K.; Grossart, Hans-Peter

    2013-01-01

    Antibiotics are chemotherapeutic agents, which have been a very powerful tool in the clinical management of bacterial diseases since the 1940s. However, benefits offered by these magic bullets have been substantially lost in subsequent days following the widespread emergence and dissemination of antibiotic-resistant strains. While it is obvious that excessive and imprudent use of antibiotics significantly contributes to the emergence of resistant strains, antibiotic resistance is also observed in natural bacteria of remote places unlikely to be impacted by human intervention. Both antibiotic biosynthetic genes and resistance-conferring genes have been known to evolve billions of years ago, long before clinical use of antibiotics. Hence it appears that antibiotics and antibiotics resistance determinants have some other roles in nature, which often elude our attention because of overemphasis on the therapeutic importance of antibiotics and the crisis imposed by the antibiotic resistance in pathogens. In the natural milieu, antibiotics are often found to be present in sub-inhibitory concentrations acting as signaling molecules supporting the process of quorum sensing and biofilm formation. They also play an important role in the production of virulence factors and influence host–parasite interactions (e.g., phagocytosis, adherence to the target cell, and so on). The evolutionary and ecological aspects of antibiotics and antibiotic resistance in the naturally occurring microbial community are little understood. Therefore, the actual role of antibiotics in nature warrants in-depth investigations. Studies on such an intriguing behavior of the microorganisms promise insight into the intricacies of the microbial physiology and are likely to provide some lead in controlling the emergence and subsequent dissemination of antibiotic resistance. This article highlights some of the recent findings on the role of antibiotics and the genes that confer resistance to antibiotics

  9. The determinants of the antibiotic resistance process

    PubMed Central

    Franco, Beatriz Espinosa; Altagracia Martínez, Marina; Sánchez Rodríguez, Martha A; Wertheimer, Albert I

    2009-01-01

    Background: The use of antibiotic drugs triggers a complex interaction involving many biological, sociological, and psychological determinants. Resistance to antibiotics is a serious worldwide problem which is increasing and has implications for morbidity, mortality, and health care both in hospitals and in the community. Objectives: To analyze current research on the determinants of antibiotic resistance and comprehensively review the main factors in the process of resistance in order to aid our understanding and assessment of this problem. Methods: We conducted a MedLine search using the key words “determinants”, “antibiotic”, and “antibiotic resistance” to identify publications between 1995 and 2007 on the determinants of antibiotic resistance. Publications that did not address the determinants of antibiotic resistance were excluded. Results: The process and determinants of antibiotic resistance are described, beginning with the development of antibiotics, resistance and the mechanisms of resistance, sociocultural determinants of resistance, the consequences of antibiotic resistance, and alternative measures proposed to combat antibiotic resistance. Conclusions: Analysis of the published literature identified the main determinants of antibiotic resistance as irrational use of antibiotics in humans and animal species, insufficient patient education when antibiotics are prescribed, lack of guidelines for treatment and control of infections, lack of scientific information for physicians on the rational use of antibiotics, and lack of official government policy on the rational use of antibiotics in public and private hospitals. PMID:21694883

  10. Advances in pneumococcal antibiotic resistance.

    PubMed

    Song, Jae-Hoon

    2013-10-01

    Antimicrobial resistance and serotypes in Streptococcus pneumoniae have been evolving with the widespread use of antibiotics and the introduction of pneumococcal conjugate vaccines (PCV). Particularly, among various types of antimicrobial resistance, macrolide resistance has most remarkably increased in many parts of the world, which has been reported to be >70% among clinical isolates from Asian countries. Penicillin resistance has dramatically decreased among nonmeningeal isolates due to the changes in resistance breakpoints, although resistance to other β-lactams such as cefuroxime has increased. Multidrug resistance became a serious concern in the treatment of invasive pneumococcal diseases, especially in Asian countries. After PCV7 vaccination, serotype 19A has emerged as an important cause of invasive pneumococcal diseases which was also associated with increasing prevalence of multidrug resistance in pneumococci. Widespread use of PCV13, which covers additional serotypes 3, 6A and 19A, may contribute to reduce the clonal spread of drug-resistant 19A pneumococci.

  11. Selection of antibiotic resistance at very low antibiotic concentrations.

    PubMed

    Sandegren, Linus

    2014-05-01

    Human use of antibiotics has driven the selective enrichment of pathogenic bacteria resistant to clinically used drugs. Traditionally, the selection of resistance has been considered to occur mainly at high, therapeutic levels of antibiotics, but we are now beginning to understand better the importance of selection of resistance at low levels of antibiotics. The concentration of an antibiotic varies in different body compartments during treatment, and low concentrations of antibiotics are found in sewage water, soils, and many water environments due to natural production and contamination from human activities. Selection of resistance at non-lethal antibiotic concentrations (below the wild-type minimum inhibitory concentration) occurs due to differences in growth rate at the particular antibiotic concentration between cells with different tolerance levels to the antibiotic. The minimum selective concentration for a particular antibiotic is reached when its reducing effect on growth of the susceptible strain balances the reducing effect (fitness cost) of the resistance determinant in the resistant strain. Recent studies have shown that resistant bacteria can be selected at concentrations several hundred-fold below the lethal concentrations for susceptible cells. Resistant mutants selected at low antibiotic concentrations are generally more fit than those selected at high concentrations but can still be highly resistant. The characteristics of selection at low antibiotic concentrations, the potential clinical problems of this mode of selection, and potential solutions will be discussed.

  12. Antibiotics and antibiotic resistance in agroecosystems: State of the science

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We propose a simple causal model depicting relationships involved in dissemination of antibiotics and antibiotic resistance in agroecosystems and potential effects on human health, functioning of natural ecosystems, and agricultural productivity. Available evidence for each causal link is briefly su...

  13. Spatial mapping of antibiotic resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A serious concern for modern animal production is the fear that feed antimicrobials, such as monensin, increase the potential for high levels of antibiotic resistant (AR) gene prevalence in the manure, which may subsequently be shared with soil communities and eventually be taken up by human pathoge...

  14. Antibiotic resistance: a geopolitical issue.

    PubMed

    Carlet, J; Pulcini, C; Piddock, L J V

    2014-10-01

    Antimicrobial resistance (AMR), associated with a lack of new antibiotics, is a major threat. Some countries have been able to contain resistance, but in most countries the numbers of antibiotic-resistant bacteria continue to increase, along with antibiotic consumption by humans and animals. AMR is a global issue, and concerns all decision-makers worldwide. Some initiatives have been undertaken in the last 15 years, in particular by the WHO, the European Centre for Disease Prevention and Control, and the CDC, but those initiatives were partial and poorly implemented, without coordination. Very recently, some important initiatives have been implemented by the WHO. Since 2009, a US and European joint task force, the Trans-Atlantic Task Force on Antibiotic Resistance, has been working on common recommendations. At a national level, some important initiatives have been implemented, in particular in European countries and in the USA. The Chennai declaration, in India, is also a good example of a multidisciplinary and national initiative that was highly political. Finally, several non-governmental non-profit organizations are also very active, and have helped to raise awareness about the problem of AMR. In the future, this global issue will need political involvement and strong cooperation between countries and between international agencies.

  15. Addressing resistance to antibiotics in systematic reviews of antibiotic interventions.

    PubMed

    Leibovici, Leonard; Paul, Mical; Garner, Paul; Sinclair, David J; Afshari, Arash; Pace, Nathan Leon; Cullum, Nicky; Williams, Hywel C; Smyth, Alan; Skoetz, Nicole; Del Mar, Chris; Schilder, Anne G M; Yahav, Dafna; Tovey, David

    2016-09-01

    Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews.

  16. Persistence and resistance as complementary bacterial adaptations to antibiotics.

    PubMed

    Vogwill, T; Comfort, A C; Furió, V; MacLean, R C

    2016-06-01

    Bacterial persistence represents a simple of phenotypic heterogeneity, whereby a proportion of cells in an isogenic bacterial population can survive exposure to lethal stresses such as antibiotics. In contrast, genetically based antibiotic resistance allows for continued growth in the presence of antibiotics. It is unclear, however, whether resistance and persistence are complementary or alternative evolutionary adaptations to antibiotics. Here, we investigate the co-evolution of resistance and persistence across the genus Pseudomonas using comparative methods that correct for phylogenetic nonindependence. We find that strains of Pseudomonas vary extensively in both their intrinsic resistance to antibiotics (ciprofloxacin and rifampicin) and persistence following exposure to these antibiotics. Crucially, we find that persistence correlates positively to antibiotic resistance across strains. However, we find that different genes control resistance and persistence implying that they are independent traits. Specifically, we find that the number of type II toxin-antitoxin systems (TAs) in the genome of a strain is correlated to persistence, but not resistance. Our study shows that persistence and antibiotic resistance are complementary, but independent, evolutionary adaptations to stress and it highlights the key role played by TAs in the evolution of persistence.

  17. Antibiotic resistance in the opportunistic pathogen Stenotrophomonas maltophilia.

    PubMed

    Sánchez, María B

    2015-01-01

    Stenotrophomonas maltophilia is an environmental bacterium found in the soil, associated with plants and animals, and in aquatic environments. It is also an opportunistic pathogen now causing an increasing number of nosocomial infections. The treatment of S. maltophilia is quite difficult given its intrinsic resistance to a number of antibiotics, and because it is able to acquire new resistances via horizontal gene transfer and mutations. Certainly, strains resistant to quinolones, cotrimoxale and/or cephalosporins-antibiotics commonly used to treat S. maltophilia infections-have emerged. The increasing number of available S. maltophilia genomes has allowed the identification and annotation of a large number of antimicrobial resistance genes. Most encode inactivating enzymes and efflux pumps, but information on their role in intrinsic and acquired resistance is limited. Non-typical antibiotic resistance mechanisms that also form part of the intrinsic resistome have been identified via mutant library screening. These include non-typical antibiotic resistance genes, such as bacterial metabolism genes, and non-inheritable resistant phenotypes, such as biofilm formation and persistence. Their relationships with resistance are complex and require further study.

  18. Environmental and Public Health Implications of Water Reuse: Antibiotics, Antibiotic Resistant Bacteria, and Antibiotic Resistance Genes

    PubMed Central

    Hong, Pei-Ying; Al-Jassim, Nada; Ansari, Mohd Ikram; Mackie, Roderick I.

    2013-01-01

    Water scarcity is a global problem, and is particularly acute in certain regions like Africa, the Middle East, as well as the western states of America. A breakdown on water usage revealed that 70% of freshwater supplies are used for agricultural irrigation. The use of reclaimed water as an alternative water source for agricultural irrigation would greatly alleviate the demand on freshwater sources. This paradigm shift is gaining momentum in several water scarce countries like Saudi Arabia. However, microbial problems associated with reclaimed water may hinder the use of reclaimed water for agricultural irrigation. Of particular concern is that the occurrence of antibiotic residues in the reclaimed water can select for antibiotic resistance genes among the microbial community. Antibiotic resistance genes can be associated with mobile genetic elements, which in turn allow a promiscuous transfer of resistance traits from one bacterium to another. Together with the pathogens that are present in the reclaimed water, antibiotic resistant bacteria can potentially exchange mobile genetic elements to create the “perfect microbial storm”. Given the significance of this issue, a deeper understanding of the occurrence of antibiotics in reclaimed water, and their potential influence on the selection of resistant microorganisms would be essential. In this review paper, we collated literature over the past two decades to determine the occurrence of antibiotics in municipal wastewater and livestock manure. We then discuss how these antibiotic resistant bacteria may impose a potential microbial risk to the environment and public health, and the knowledge gaps that would have to be addressed in future studies. Overall, the collation of the literature in wastewater treatment and agriculture serves to frame and identify potential concerns with respect to antibiotics, antibiotic resistant bacteria, and antibiotic resistance genes in reclaimed water. PMID:27029309

  19. Antibiotic resistance in cancer patients.

    PubMed

    Gudiol, Carlota; Carratalà, Jordi

    2014-08-01

    Bacterial infection is one of the most frequent complications in cancer patients and hematopoietic stem cell transplant recipients. In recent years, the emergence of antimicrobial resistance has become a significant problem worldwide, and cancer patients are among those affected. Treatment of infections due to multidrug-resistant (MDR) bacteria represents a clinical challenge, especially in the case of Gram-negative bacilli, since the therapeutic options are often very limited. As the antibiotics active against MDR bacteria present several disadvantages (limited clinical experience, higher incidence of adverse effects, and less knowledge of the pharmacokinetics of the drug), a thorough acquaintance with the main characteristics of these drugs is mandatory in order to provide safe treatment to cancer patients with MDR bacterial infections. Nevertheless, the implementation of antibiotic stewardship programs and infection control measures is the cornerstone for controlling the development and spread of these MDR pathogens.

  20. Intrinsic novobiocin resistance in Staphylococcus saprophyticus.

    PubMed

    Vickers, Anna A; Chopra, Ian; O'Neill, Alex J

    2007-12-01

    Intrinsic novobiocin resistance in Staphylococcus saprophyticus was associated with expression of a novobiocin-resistant form of the drug target protein (GyrB). Site-directed mutagenesis established that resistance depends upon the presence of two specific amino acid residues in GyrB: a glycine at position 85 and a lysine at position 140.

  1. Resistance to Antibiotics Mediated by Target Alterations

    NASA Astrophysics Data System (ADS)

    Spratt, Brian G.

    1994-04-01

    The development of resistance to antibiotics by reductions in the affinities of their enzymatic targets occurs most rapidly for antibiotics that inactivate a single target and that are not analogs of substrate. In these cases of resistance (for example, resistance to rifampicin), numerous single amino acid substitutions may provide large decreases in the affinity of the target for the antibiotic, leading to clinically significant levels of resistance. Resistance due to target alterations should occur much more slowly for those antibiotics (penicillin, for example) that inactivate multiple targets irreversibly by acting as close analogs of substrate. Resistance to penicillin because of target changes has emerged, by unexpected mechanisms, only in a limited number of species. However, inactivating enzymes commonly provide resistance to antibiotics that, like penicillin, are derived from natural products, although such enzymes have not been found for synthetic antibiotics. Thus, the ideal antibiotic would be produced by rational design, rather than by the modification of a natural product.

  2. Origins and evolution of antibiotic resistance.

    PubMed

    Davies, Julian; Davies, Dorothy

    2010-09-01

    Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory.

  3. Origins and Evolution of Antibiotic Resistance

    PubMed Central

    Davies, Julian; Davies, Dorothy

    2010-01-01

    Summary: Antibiotics have always been considered one of the wonder discoveries of the 20th century. This is true, but the real wonder is the rise of antibiotic resistance in hospitals, communities, and the environment concomitant with their use. The extraordinary genetic capacities of microbes have benefitted from man's overuse of antibiotics to exploit every source of resistance genes and every means of horizontal gene transmission to develop multiple mechanisms of resistance for each and every antibiotic introduced into practice clinically, agriculturally, or otherwise. This review presents the salient aspects of antibiotic resistance development over the past half-century, with the oft-restated conclusion that it is time to act. To achieve complete restitution of therapeutic applications of antibiotics, there is a need for more information on the role of environmental microbiomes in the rise of antibiotic resistance. In particular, creative approaches to the discovery of novel antibiotics and their expedited and controlled introduction to therapy are obligatory. PMID:20805405

  4. Probiotic approach to prevent antibiotic resistance.

    PubMed

    Ouwehand, Arthur C; Forssten, Sofia; Hibberd, Ashley A; Lyra, Anna; Stahl, Buffy

    2016-01-01

    Probiotics are live microorganisms, mainly belonging to the genera Lactobacillus and Bifidobacterium, although also strain of other species are commercialized, that have a beneficial effect on the host. From the perspective of antibiotic use, probiotics have been observed to reduce the risk of certain infectious disease such as certain types of diarrhea and respiratory tract infection. This may be accompanied with a reduced need of antibiotics for secondary infections. Antibiotics tend to be effective against most common diseases, but increasingly resistance is being observed among pathogens. Probiotics are specifically selected to not contribute to the spread of antibiotic resistance and not carry transferable antibiotic resistance. Concomitant use of probiotics with antibiotics has been observed to reduce the incidence, duration and/or severity of antibiotic-associated diarrhea. This contributes to better adherence to the antibiotic prescription and thereby reduces the evolution of resistance. To what extent probiotics directly reduce the spread of antibiotic resistance is still much under investigation; but maintaining a balanced microbiota during antibiotic use may certainly provide opportunities for reducing the spread of resistances. Key messages Probiotics may reduce the risk for certain infectious diseases and thereby reduce the need for antibiotics. Probiotics may reduce the risk for antibiotic-associated diarrhea Probiotics do not contribute to the spread of antibiotic resistance and may even reduce it.

  5. What Can Be Done about Antibiotic Resistance?

    MedlinePlus

    ... Us General Background: What can be done about Antibiotic Resistance? What can I do? Are antibacterial agents, such as antibacterial soaps, a solution? Are antibiotics regulated? Is there any international action on the ...

  6. Insights into antibiotic resistance through metagenomic approaches.

    PubMed

    Schmieder, Robert; Edwards, Robert

    2012-01-01

    The consequences of bacterial infections have been curtailed by the introduction of a wide range of antibiotics. However, infections continue to be a leading cause of mortality, in part due to the evolution and acquisition of antibiotic-resistance genes. Antibiotic misuse and overprescription have created a driving force influencing the selection of resistance. Despite the problem of antibiotic resistance in infectious bacteria, little is known about the diversity, distribution and origins of resistance genes, especially for the unculturable majority of environmental bacteria. Functional and sequence-based metagenomics have been used for the discovery of novel resistance determinants and the improved understanding of antibiotic-resistance mechanisms in clinical and natural environments. This review discusses recent findings and future challenges in the study of antibiotic resistance through metagenomic approaches.

  7. Antibiotic use and resistance in animals: Belgian initiatives.

    PubMed

    Daeseleire, Els; De Graef, Evelyne; Rasschaert, Geertrui; De Mulder, Thijs; Van den Meersche, Tina; Van Coillie, Els; Dewulf, Jeroen; Heyndrickx, Marc

    2016-05-01

    The widespread use of antibiotics in animals is causing concerns about the growing risk for development and the spread of antibiotic-resistant bacteria. Antibiotic consumption is higher in animals than in humans as reported in a joint publication of EFSA (European Food Safety Agency), ECDC (European Centre for Disease Prevention and Control), and EMA (European Medicines Agency) using data from 2011 and 2012. Both in humans and animals, positive associations between the consumption of antibiotics and resistant bacteria are observed. Responsible use of antibiotics in humans and animals should therefore be promoted. In this paper some general aspects of antibiotic resistance such as microbiological versus clinical resistance, intrinsic versus acquired resistance, resistance mechanisms, and transfer of resistance are briefly introduced. In 2012, the Belgian Center of Expertise on Antimicrobial Consumption and Resistance in Animals (AMCRA) was founded. Its mission is to collect and analyze all data related to antibiotic use and resistance in animals in Belgium and to communicate these findings in a neutral and objective manner. One of AMCRA's 10 objectives is a 50% reduction in antibiotic consumption in veterinary medicine in Belgium by 2020. The aim of this paper is to report on the achievements of this national project. The Institute for Agricultural and Fisheries Research (ILVO, Merelbeke-Melle), in collaboration with Ghent University, is currently working on three nationally funded projects on antibiotic resistance in animal husbandry. In the first project, an in vitro model is used to study the influence of low antibiotic concentrations due to carry-over after production and usage of medicated feed on the development of resistance in the pig gut. Part of that project is to develop a quantitative risk assessment model. A second project focuses on tracking excreted antibiotics used in pig rearing and their influence on the development of antibiotic resistance in pig

  8. Adjuvant strategies for potentiation of antibiotics to overcome antimicrobial resistance.

    PubMed

    Pieren, Michel; Tigges, Marcel

    2012-10-01

    Alarming facts about the occurrence and spreading of multiple antibiotic resistant bacteria have caught the attention of global surveillance authorities and public media. The demand for novel effective antimicrobial drugs is high and on the rise while, at the same time, the supply of fresh 'magic bullets' is drying up. This review summarizes examples of recent strategies for development of adjunctive antibiotic therapies that overcome microbial resistance and thus rejuvenate the existing arsenal of drugs. Recent studies have demonstrated the potential of compounds that inhibit the action of the repressor protein implicated in ethionamide resistance, thus stimulating activation of the drug and thereby restoring the activity of the antibiotic for treatment of Mycobacterium tuberculosis. Such specific interference with regulators or signal transduction mechanisms involved in antibiotic resistance or virulence provides a new toolbox for novel combinations of antimicrobial drugs with adjuvant molecules lacking intrinsic antibiotic activity. In addition to the development of new antibiotics and vaccination initiatives this strategy of restoring or potentiating the activity of existing antibiotics may help to postpone the day when antibiotics are no longer generally efficacious.

  9. Tackling antibiotic resistance: the environmental framework.

    PubMed

    Berendonk, Thomas U; Manaia, Célia M; Merlin, Christophe; Fatta-Kassinos, Despo; Cytryn, Eddie; Walsh, Fiona; Bürgmann, Helmut; Sørum, Henning; Norström, Madelaine; Pons, Marie-Noëlle; Kreuzinger, Norbert; Huovinen, Pentti; Stefani, Stefania; Schwartz, Thomas; Kisand, Veljo; Baquero, Fernando; Martinez, José Luis

    2015-05-01

    Antibiotic resistance is a threat to human and animal health worldwide, and key measures are required to reduce the risks posed by antibiotic resistance genes that occur in the environment. These measures include the identification of critical points of control, the development of reliable surveillance and risk assessment procedures, and the implementation of technological solutions that can prevent environmental contamination with antibiotic resistant bacteria and genes. In this Opinion article, we discuss the main knowledge gaps, the future research needs and the policy and management options that should be prioritized to tackle antibiotic resistance in the environment.

  10. Mechanisms of Resistance to Aminoglycoside Antibiotics: Overview and Perspectives

    PubMed Central

    Garneau-Tsodikova, Sylvie

    2015-01-01

    Aminoglycoside (AG) antibiotics are used to treat many Gram-negative and some Gram-positive infections and, importantly, multidrug-resistant tuberculosis. Among various bacterial species, resistance to AGs arises through a variety of intrinsic and acquired mechanisms. The bacterial cell wall serves as a natural barrier for small molecules such as AGs and may be further fortified via acquired mutations. Efflux pumps work to expel AGs from bacterial cells, and modifications here too may cause further resistance to AGs. Mutations in the ribosomal target of AGs, while rare, also contribute to resistance. Of growing clinical prominence is resistance caused by ribosome methyltransferases. By far the most widespread mechanism of resistance to AGs is the inactivation of these antibiotics by AG-modifying enzymes. We provide here an overview of these mechanisms by which bacteria become resistant to AGs and discuss their prevalence and potential for clinical relevance. PMID:26877861

  11. Antibiotics and Bacterial Resistance in the 21st Century

    PubMed Central

    Fair, Richard J; Tor, Yitzhak

    2014-01-01

    Dangerous, antibiotic resistant bacteria have been observed with increasing frequency over the past several decades. In this review the factors that have been linked to this phenomenon are addressed. Profiles of bacterial species that are deemed to be particularly concerning at the present time are illustrated. Factors including economic impact, intrinsic and acquired drug resistance, morbidity and mortality rates, and means of infection are taken into account. Synchronously with the waxing of bacterial resistance there has been waning antibiotic development. The approaches that scientists are employing in the pursuit of new antibacterial agents are briefly described. The standings of established antibiotic classes as well as potentially emerging classes are assessed with an emphasis on molecules that have been clinically approved or are in advanced stages of development. Historical perspectives, mechanisms of action and resistance, spectrum of activity, and preeminent members of each class are discussed. PMID:25232278

  12. Update on the antibiotic resistance crisis.

    PubMed

    Rossolini, Gian Maria; Arena, Fabio; Pecile, Patrizia; Pollini, Simona

    2014-10-01

    Antibiotics tend to lose their efficacy over time due to the emergence and dissemination of resistance among bacterial pathogens. Strains with resistance to multiple antibiotic classes have emerged among major Gram-positive and Gram-negative species including Staphylococcus aureus, Enterococcus spp., Pseudomonas aeruginosa, Acinetobacter spp. Enterobacteriaceae, and Neisseria gonorrhoeae. With some Gram-negatives, resistance may involve most or even all the available antimicrobial options, resulting in extremely drug-resistant or totally drug-resistant phenotypes. This so-called 'antibiotic resistance crisis' has been compounded by the lagging in antibiotic discovery and development programs occurred in recent years, and is jeopardizing the essential role played by antibiotics in current medical practices.

  13. Antibiotic resistance: a physicist’s view

    NASA Astrophysics Data System (ADS)

    Allen, Rosalind; Waclaw, Bartłomiej

    2016-08-01

    The problem of antibiotic resistance poses challenges across many disciplines. One such challenge is to understand the fundamental science of how antibiotics work, and how resistance to them can emerge. This is an area where physicists can make important contributions. Here, we highlight cases where this is already happening, and suggest directions for further physics involvement in antimicrobial research.

  14. Antibiotic resistance: a physicist’s view

    PubMed Central

    Allen, Rosalind; Waclaw, Bartłomiej

    2016-01-01

    The problem of antibiotic resistance poses challenges across many disciplines. One such challenge is to understand the fundamental science of how antibiotics work, and how resistance to them can emerge. This is an area where physicists can make important contributions. Here, we highlight cases where this is already happening, and suggest directions for further physics involvement in antimicrobial research. PMID:27510596

  15. Background antibiotic resistance patterns in antibiotic-free pastured poultry production

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotic resistance (AR) is a significant public health issue, and agroecosystems are often viewed as major environmental sources of antibiotic resistant foodborne pathogens. While the use of antibiotics in agroecosystems can potentially increase AR, appropriate background resistance levels in th...

  16. A review of the influence of treatment strategies on antibiotic resistant bacteria and antibiotic resistance genes.

    PubMed

    Sharma, Virender K; Johnson, Natalie; Cizmas, Leslie; McDonald, Thomas J; Kim, Hyunook

    2016-05-01

    Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARG) in the aquatic environment have become an emerging contaminant issue, which has implications for human and ecological health. This review begins with an introduction to the occurrence of ARB and ARG in different environmental systems such as natural environments and drinking water resources. For example, ARG or ARB with resistance to ciprofloxacin, sulfamethoxazole, trimethoprim, quinolone, vancomycin, or tetracycline (e.g., tet(A), tet(B), tet(C), tet(G), tet(O), tet(M), tet(W), sul I, and sul II) have been detected in the environment. The development of resistance may be intrinsic, may be acquired through spontaneous mutations (de novo), or may occur due to horizontal gene transfer from donor bacteria, phages, or free DNA to recipient bacteria. An overview is also provided of the current knowledge regarding inactivation of ARB and ARG, and the mechanism of the effects of different disinfection processes in water and wastewater (chlorination, UV irradiation, Fenton reaction, ozonation, and photocatalytic oxidation). The effects of constructed wetlands and nanotechnology on ARB and ARG are also summarized.

  17. Counteracting selection for antibiotic-resistant bacteria

    PubMed Central

    Yosef, Ido; Manor, Miriam; Qimron, Udi

    2016-01-01

    ABSTRACT The occurrence of antibiotic-resistant bacterial pathogens is on the rise because antibiotics exert selection pressure that kills only the antibiotic-sensitive pathogens. Sanitation and cleansing of hospital surfaces and the skin of medical personnel do not counteract this selective pressure, but rather indiscriminately reduce total pathogens on treated surfaces. Here, we discuss two recently introduced genetic strategies, based on temperate bacteriophages as DNA-delivery vehicles, that aim to sensitize bacteria to antibiotics and selectively kill the antibiotic-resistant ones. Outlooks for rendering one such approach more efficient and applicable are proposed. We believe that using an end product designed according to the provided principles on hospital surfaces and in hand-sanitizers will facilitate substitution of antibiotic-resistant pathogens with sensitive ones. PMID:27144084

  18. Antibiotic Resistance in Pediatric Urinary Tract Infections.

    PubMed

    Stultz, Jeremy S; Doern, Christopher D; Godbout, Emily

    2016-12-01

    Urinary tract infections (UTIs) are a common problem in pediatric patients. Resistance to common antibiotic agents appears to be increasing over time, although resistance rates may vary based on geographic region or country. Prior antibiotic exposure is a pertinent risk factor for acquiring resistant organisms during a first UTI and recurrent UTI. Judicious prescribing of antibiotics for common pediatric conditions is needed to prevent additional resistance from occurring. Complex pediatric patients with histories of hospitalizations, prior antibiotic exposure, and recurrent UTIs are also at high risk for acquiring UTIs due to extended spectrum beta-lactamase-producing organisms. Data regarding the impact of in vitro antibiotic susceptibility testing interpretation on UTI treatment outcomes is lacking.

  19. Persistence of antibiotic resistance in bacterial populations.

    PubMed

    Andersson, Dan I; Hughes, Diarmaid

    2011-09-01

    Unfortunately for mankind, it is very likely that the antibiotic resistance problem we have generated during the last 60 years due to the extensive use and misuse of antibiotics is here to stay for the foreseeable future. This view is based on theoretical arguments, mathematical modeling, experiments and clinical interventions, suggesting that even if we could reduce antibiotic use, resistant clones would remain persistent and only slowly (if at all) be outcompeted by their susceptible relatives. In this review, we discuss the multitude of mechanisms and processes that are involved in causing the persistence of chromosomal and plasmid-borne resistance determinants and how we might use them to our advantage to increase the likelihood of reversing the problem. Of particular interest is the recent demonstration that a very low antibiotic concentration can be enriching for resistant bacteria and the implication that antibiotic release into the environment could contribute to the selection for resistance. Several mechanisms are contributing to the stability of antibiotic resistance in bacterial populations and even if antibiotic use is reduced it is likely that most resistance mechanisms will persist for considerable times.

  20. Antibiotic combinations for controlling colistin-resistant Enterobacter cloacae.

    PubMed

    Lima, Thais Bergamin; Silva, Osmar Nascimento; de Almeida, Keyla Caroline; Ribeiro, Suzana Meira; Motta, Dielle de Oliveira; Maria-Neto, Simone; Lara, Michelle Brizolla; Filho, Carlos Roberto Souza; Ombredane, Alicia Simalie; de Faria Junior, Celio; Parachin, Nadia Skorupa; Magalhães, Beatriz Simas; Franco, Octávio Luiz

    2017-02-01

    Enterobacter cloacae is a Gram-negative bacterium associated with high morbidity and mortality in intensive care patients due to its resistance to multiple antibiotics. Currently, therapy against multi-resistant bacteria consists of using colistin, in spite of its toxic effects at higher concentrations. In this context, colistin-resistant E. cloacae strains were challenged with lower levels of colistin combined with other antibiotics to reduce colistin-associated side effects. Colistin-resistant E. cloacae (ATCC 49141) strains were generated by serial propagation in subinhibitory colistin concentrations. After this, three colistin-resistant and three nonresistant replicates were isolated. The identity of all the strains was confirmed by MALDI-TOF MS, VITEK 2 and MicroScan analysis. Furthermore, cross-resistance to other antibiotics was checked by disk diffusion and automated systems. The synergistic effects of the combined use of colistin and chloramphenicol were observed via the broth microdilution checkerboard method. First, data here reported showed that all strains presented intrinsic resistance to penicillin, cephalosporin (except fourth generation), monobactam, and some associations of penicillin and β-lactamase inhibitors. Moreover, a chloramphenicol and colistin combination was capable of inhibiting the induced colistin-resistant strains as well as two colistin-resistant clinical strains. Furthermore, no cytotoxic effect was observed by using such concentrations. In summary, the data reported here showed for the first time the possible therapeutic use of colistin-chloramphenicol for infections caused by colistin-resistant E. cloacae.

  1. Antibiotic resistance: are we all doomed?

    PubMed

    Collignon, P

    2015-11-01

    Antibiotic resistance is a growing and worrying problem associated with increased deaths and suffering for people. Overall, there are only two factors that drive antimicrobial resistance, and both can be controlled. These factors are the volumes of antimicrobials used and the spread of resistant micro-organisms and/or the genes encoding for resistance. The One Health concept is important if we want to understand better and control antimicrobial resistance. There are many things we can do to better control antimicrobial resistance. We need to prevent infections. We need to have better surveillance with good data on usage patterns and resistance patterns available across all sectors, both human and agriculture, locally and internationally. We need to act on these results when we see either inappropriate usage or resistance levels rising in bacteria that are of concern for people. We need to ensure that food and water sources do not spread multi-resistant micro-organisms or resistance genes. We need better approaches to restrict successfully what and how antibiotics are used in people. We need to restrict the use of 'critically important' antibiotics in food animals and the entry of these drugs into the environment. We need to ensure that 'One Health' concept is not just a buzz word but implemented. We need to look at all sectors and control not only antibiotic use but also the spread and development of antibiotic resistant bacteria - both locally and internationally.

  2. Mechanisms of antibiotic resistance in enterococci

    PubMed Central

    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

  3. Antibiotic Resistance Related to Biofilm Formation in Klebsiella pneumoniae

    PubMed Central

    Vuotto, Claudia; Longo, Francesca; Balice, Maria Pia; Donelli, Gianfranco; Varaldo, Pietro E.

    2014-01-01

    The Gram-negative opportunistic pathogen, Klebsiella pneumoniae, is responsible for causing a spectrum of community-acquired and nosocomial infections and typically infects patients with indwelling medical devices, especially urinary catheters, on which this microorganism is able to grow as a biofilm. The increasingly frequent acquisition of antibiotic resistance by K. pneumoniae strains has given rise to a global spread of this multidrug-resistant pathogen, mostly at the hospital level. This scenario is exacerbated when it is noted that intrinsic resistance to antimicrobial agents dramatically increases when K. pneumoniae strains grow as a biofilm. This review will summarize the findings about the antibiotic resistance related to biofilm formation in K. pneumoniae. PMID:25438022

  4. Antibiotic tolerance facilitates the evolution of resistance.

    PubMed

    Levin-Reisman, Irit; Ronin, Irine; Gefen, Orit; Braniss, Ilan; Shoresh, Noam; Balaban, Nathalie Q

    2017-02-24

    Controlled experimental evolution during antibiotic treatment can help to explain the processes leading to antibiotic resistance in bacteria. Recently, intermittent antibiotic exposures have been shown to lead rapidly to the evolution of tolerance-that is, the ability to survive under treatment without developing resistance. However, whether tolerance delays or promotes the eventual emergence of resistance is unclear. Here we used in vitro evolution experiments to explore this question. We found that in all cases, tolerance preceded resistance. A mathematical population-genetics model showed how tolerance boosts the chances for resistance mutations to spread in the population. Thus, tolerance mutations pave the way for the rapid subsequent evolution of resistance. Preventing the evolution of tolerance may offer a new strategy for delaying the emergence of resistance.

  5. Boosting bacterial metabolism to combat antibiotic resistance.

    PubMed

    Bhargava, Prerna; Collins, James J

    2015-02-03

    The metabolic state of a bacterial cell influences its susceptibility to antibiotics. In this issue, Peng et al. (2015) show that resistant bacteria can be sensitized to antibiotic treatment through the addition of exogenous metabolites that stimulate central metabolic pathways and increase drug uptake.

  6. Mining metagenomic datasets for antibiotic resistance genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotics are medicines that are used to kill, slow down, or prevent the growth of susceptible bacteria. They became widely used in the mid 20th century for controlling disease in humans, animals, and plants, and for a variety of industrial purposes. Antibiotic resistance is a broad term. There ...

  7. The Antibiotic Resistance Problem Revisited

    ERIC Educational Resources Information Center

    Lawson, Michael A.

    2008-01-01

    The term "antibiotic" was first proposed by Vuillemin in 1889 but was first used in the current sense by Walksman in 1941. An antibiotic is defined as a "derivative produced by the metabolism of microorganisms that possess antibacterial activity at low concentrations and is not toxic to the host." In this article, the author describes how…

  8. Intrinsic radiation resistance in human chondrosarcoma cells

    SciTech Connect

    Moussavi-Harami, Farid; Mollano, Anthony; Martin, James A.; Ayoob, Andrew; Domann, Frederick E.; Gitelis, Steven; Buckwalter, Joseph A. . E-mail: joseph-buckwalter@uiowa.edu

    2006-07-28

    Human chondrosarcomas rarely respond to radiation treatment, limiting the options for eradication of these tumors. The basis of radiation resistance in chondrosarcomas remains obscure. In normal cells radiation induces DNA damage that leads to growth arrest or death. However, cells that lack cell cycle control mechanisms needed for these responses show intrinsic radiation resistance. In previous work, we identified immortalized human chondrosarcoma cell lines that lacked p16{sup ink4a}, one of the major tumor suppressor proteins that regulate the cell cycle. We hypothesized that the absence of p16{sup ink4a} contributes to the intrinsic radiation resistance of chondrosarcomas and that restoring p16{sup ink4a} expression would increase their radiation sensitivity. To test this we determined the effects of ectopic p16{sup ink4a} expression on chondrosarcoma cell resistance to low-dose {gamma}-irradiation (1-5 Gy). p16{sup ink4a} expression significantly increased radiation sensitivity in clonogenic assays. Apoptosis did not increase significantly with radiation and was unaffected by p16{sup ink4a} transduction of chondrosarcoma cells, indicating that mitotic catastrophe, rather than programmed cell death, was the predominant radiation effect. These results support the hypothesis that p16{sup ink4a} plays a role in the radiation resistance of chondrosarcoma cell lines and suggests that restoring p16 expression will improve the radiation sensitivity of human chondrosarcomas.

  9. Management Options For Reducing The Release Of Antibiotics And Antibiotic Resistance Genes To The Environment

    EPA Science Inventory

    Background: There is growing concern worldwide about the role of polluted soil and water - 77 environments in the development and dissemination of antibiotic resistance. 78 Objective: To identify management options for reducing the spread of antibiotics and 79 antibiotic resist...

  10. WAAR (World Alliance against Antibiotic Resistance): Safeguarding antibiotics

    PubMed Central

    2012-01-01

    Summary Resistance to antibiotics has increased recently to a dramatic extend, and the pipeline of new antibiotics is almost dry for the five next years. Failures happen already for trivial community acquired infections, like pyelonephritis, or peritonitis, and this is likely to increase. Difficult surgical procedures, transplants, and other immunosuppressive therapies will become far more risky. Resistance is mainly due to an excessive usage of antibiotics, in all sectors, including the animal one. Action is urgently needed. Therefore, an alliance against MDRO has been recently created, which includes health care professionals, consumers, health managers, and politicians. The document highlights the different proposed measures, and represents a strong consensus between the different professionals, including general practicionners, and veterinarians. PMID:22958542

  11. Therapeutic strategies to combat antibiotic resistance.

    PubMed

    Brooks, Benjamin D; Brooks, Amanda E

    2014-11-30

    With multidrug resistant bacteria on the rise, new antibiotic approaches are required. Although a number of new small molecule antibiotics are currently in the development pipeline with many more in preclinical development, the clinical options and practices for infection control must be expanded. Biologics and non-antibiotic adjuvants offer this opportunity for expansion. Nevertheless, to avoid known mechanisms of resistance, intelligent combination approaches for multiple simultaneous and complimentary therapies must be designed. Combination approaches should extend beyond biologically active molecules to include smart controlled delivery strategies. Infection control must integrate antimicrobial stewardship, new antibiotic molecules, biologics, and delivery strategies into effective combination therapies designed to 1) fight the infection, 2) avoid resistance, and 3) protect the natural microbiome. This review explores these developing strategies in the context of circumventing current mechanisms of resistance.

  12. Lytic phages obscure the cost of antibiotic resistance in Escherichia coli.

    PubMed

    Tazzyman, Samuel J; Hall, Alex R

    2015-03-17

    The long-term persistence of antibiotic-resistant bacteria depends on their fitness relative to other genotypes in the absence of drugs. Outside the laboratory, viruses that parasitize bacteria (phages) are ubiquitous, but costs of antibiotic resistance are typically studied in phage-free experimental conditions. We used a mathematical model and experiments with Escherichia coli to show that lytic phages strongly affect the incidence of antibiotic resistance in drug-free conditions. Under phage parasitism, the likelihood that antibiotic-resistant genetic backgrounds spread depends on their initial frequency, mutation rate and intrinsic growth rate relative to drug-susceptible genotypes, because these parameters determine relative rates of phage-resistance evolution on different genetic backgrounds. Moreover, the average cost of antibiotic resistance in terms of intrinsic growth in the antibiotic-free experimental environment was small relative to the benefits of an increased mutation rate in the presence of phages. This is consistent with our theoretical work indicating that, under phage selection, typical costs of antibiotic resistance can be outweighed by realistic increases in mutability if drug resistance and hypermutability are genetically linked, as is frequently observed in clinical isolates. This suggests the long-term distribution of antibiotic resistance depends on the relative rates at which different lineages adapt to other types of selection, which in the case of phage parasitism is probably extremely common, as well as costs of resistance inferred by classical in vitro methods.

  13. Acquired Antibiotic Resistance Genes: An Overview

    PubMed Central

    van Hoek, Angela H. A. M.; Mevius, Dik; Guerra, Beatriz; Mullany, Peter; Roberts, Adam Paul; Aarts, Henk J. M.

    2011-01-01

    In this review an overview is given on antibiotic resistance (AR) mechanisms with special attentions to the AR genes described so far preceded by a short introduction on the discovery and mode of action of the different classes of antibiotics. As this review is only dealing with acquired resistance, attention is also paid to mobile genetic elements such as plasmids, transposons, and integrons, which are associated with AR genes, and involved in the dispersal of antimicrobial determinants between different bacteria. PMID:22046172

  14. Does antifouling paint select for antibiotic resistance?

    PubMed

    Flach, Carl-Fredrik; Pal, Chandan; Svensson, Carl Johan; Kristiansson, Erik; Östman, Marcus; Bengtsson-Palme, Johan; Tysklind, Mats; Larsson, D G Joakim

    2017-07-15

    There is concern that heavy metals and biocides contribute to the development of antibiotic resistance via co-selection. Most antifouling paints contain high amounts of such substances, which risks turning painted ship hulls into highly mobile refuges and breeding grounds for antibiotic-resistant bacteria. The objectives of this study were to start investigate if heavy-metal based antifouling paints can pose a risk for co-selection of antibiotic-resistant bacteria and, if so, identify the underlying genetic basis. Plastic panels with one side painted with copper and zinc-containing antifouling paint were submerged in a Swedish marina and biofilms from both sides of the panels were harvested after 2.5-4weeks. DNA was isolated from the biofilms and subjected to metagenomic sequencing. Biofilm bacteria were cultured on marine agar supplemented with tetracycline, gentamicin, copper sulfate or zinc sulfate. Biofilm communities from painted surfaces displayed lower taxonomic diversity and enrichment of Gammaproteobacteria. Bacteria from these communities showed increased resistance to both heavy metals and tetracycline but not to gentamicin. Significantly higher abundance of metal and biocide resistance genes was observed, whereas mobile antibiotic resistance genes were not enriched in these communities. In contrast, we found an enrichment of chromosomal RND efflux system genes, including such with documented ability to confer decreased susceptibility to both antibiotics and biocides/heavy metals. This was paralleled by increased abundances of integron-associated integrase and ISCR transposase genes. The results show that the heavy metal-based antifouling paint exerts a strong selection pressure on marine bacterial communities and can co-select for certain antibiotic-resistant bacteria, likely by favoring species and strains carrying genes that provide cross-resistance. Although this does not indicate an immediate risk for promotion of mobile antibiotic resistance, the

  15. Assessing Antibiotic Resistance of Staphyloccocus: Students Use Their Own Microbial Flora To Explore Antibiotic Resistance.

    ERIC Educational Resources Information Center

    Omoto, Charlotte K.; Malm, Kirstin

    2003-01-01

    Describes a microbiology laboratory experiment in which students test their own microbial flora of Staphylococcus for antibiotic resistance. Provides directions on how to conduct the experiment. (YDS)

  16. Curing bacteria of antibiotic resistance: reverse antibiotics, a novel class of antibiotics in nature.

    PubMed

    Hiramatsu, Keiichi; Igarashi, Masayuki; Morimoto, Yuh; Baba, Tadashi; Umekita, Maya; Akamatsu, Yuzuru

    2012-06-01

    By screening cultures of soil bacteria, we re-discovered an old antibiotic (nybomycin) as an antibiotic with a novel feature. Nybomycin is active against quinolone-resistant Staphylococcus aureus strains with mutated gyrA genes but not against those with intact gyrA genes against which quinolone antibiotics are effective. Nybomycin-resistant mutant strains were generated from a quinolone-resistant, nybomycin-susceptible, vancomycin-intermediate S. aureus (VISA) strain Mu 50. The mutants, occurring at an extremely low rate (<1 × 10(-11)/generation), were found to have their gyrA genes back-mutated and to have lost quinolone resistance. Here we describe nybomycin as the first member of a novel class of antibiotics designated 'reverse antibiotics'.

  17. Antibiotic resistance: Italian awareness survey 2016.

    PubMed

    Prigitano, Anna; Romanò, Luisa; Auxilia, Francesco; Castaldi, Silvana; Tortorano, Anna M

    2017-03-09

    Antimicrobial resistance has become a public health priority worldwide. The WHO conducted a survey concerning the personal use of antibiotics, knowledge of appropriate use and awareness of the issue of resistance. A similar survey was conducted in Italy involving 666 young university students and 131 seniors attending courses of the University of the third age. Antibiotics seem to be taken with moderate frequency and appropriately: 30% of respondents took them in the past six months and 94% took these drugs only prescribed by a doctor, in the correct dose and for the proper duration. Notable confusion concerning the conditions treatable with antibiotics was detected (only 30% indicated gonorrhea, and 30-40% believed that antibiotics should be employed for fever, cold, and flu), while 94% of participants seemed aware of the problem of antibiotic resistance. Most of the respondents identified the behaviors that can reduce the phenomenon of resistance (regular handwashing and use of antibiotics only when prescribed and needed). The results of our survey, that involved people of high level of instruction and living in urban areas of northern regions, cannot be extended to all the Italian population. However, they provide valid elements to promote initiatives aimed to a more aware use of antibiotics.

  18. The genomic enzymology of antibiotic resistance.

    PubMed

    Morar, Mariya; Wright, Gerard D

    2010-01-01

    The need for new antibiotic therapies is acute and growing in large part because of the emergence of drug-resistant pathogens. A vast number of resistance determinants are, however, found in nonpathogenic micro-organisms. The resistance totality in the global microbiota is the antibiotic resistome and includes not only established resistance genes but also genes that have the potential to evolve into resistance elements. We term these proto-resistance genes and hypothesize that they share common ancestry with other functional units known as housekeeping genes. Genomic enzymology is the study of protein structure-function in light of genetic context and evolution of protein superfamilies. This concept is highly applicable to study of antibiotic resistance evolution from proto-resistance elements. In this review, we summarize some of the genomic enzymology evidence for resistance enzymes pointing to common ancestry with genes of other metabolic functions. Genomic enzymology plays a key role in understanding the origins of antibiotic resistance and aids in designing strategies for diagnosis and prevention thereof.

  19. The fitness costs of antibiotic resistance mutations

    PubMed Central

    Melnyk, Anita H; Wong, Alex; Kassen, Rees

    2015-01-01

    Antibiotic resistance is increasing in pathogenic microbial populations and is thus a major threat to public health. The fate of a resistance mutation in pathogen populations is determined in part by its fitness. Mutations that suffer little or no fitness cost are more likely to persist in the absence of antibiotic treatment. In this review, we performed a meta-analysis to investigate the fitness costs associated with single mutational events that confer resistance. Generally, these mutations were costly, although several drug classes and species of bacteria on average did not show a cost. Further investigations into the rate and fitness values of compensatory mutations that alleviate the costs of resistance will help us to better understand both the emergence and management of antibiotic resistance in clinical settings. PMID:25861385

  20. Transfer of antibiotic-resistance genes via phage-related mobile elements.

    PubMed

    Brown-Jaque, Maryury; Calero-Cáceres, William; Muniesa, Maite

    2015-05-01

    Antibiotic resistance is a major concern for society because it threatens the effective prevention of infectious diseases. While some bacterial strains display intrinsic resistance, others achieve antibiotic resistance by mutation, by the recombination of foreign DNA into the chromosome or by horizontal gene acquisition. In many cases, these three mechanisms operate together. Several mobile genetic elements (MGEs) have been reported to mobilize different types of resistance genes and despite sharing common features, they are often considered and studied separately. Bacteriophages and phage-related particles have recently been highlighted as MGEs that transfer antibiotic resistance. This review focuses on phages, phage-related elements and on composite MGEs (phages-MGEs) involved in antibiotic resistance mobility. We review common features of these elements, rather than differences, and provide a broad overview of the antibiotic resistance transfer mechanisms observed in nature, which is a necessary first step to controlling them.

  1. Collateral sensitivity of antibiotic-resistant microbes.

    PubMed

    Pál, Csaba; Papp, Balázs; Lázár, Viktória

    2015-07-01

    Understanding how evolution of microbial resistance towards a given antibiotic influences susceptibility to other drugs is a challenge of profound importance. By combining laboratory evolution, genome sequencing, and functional analyses, recent works have charted the map of evolutionary trade-offs between antibiotics and have explored the underlying molecular mechanisms. Strikingly, mutations that caused multidrug resistance in bacteria simultaneously enhanced sensitivity to many other unrelated drugs (collateral sensitivity). Here, we explore how this emerging research sheds new light on resistance mechanisms and the way it could be exploited for the development of alternative antimicrobial strategies.

  2. Antibiotic-Resistant Vibrios in Farmed Shrimp

    PubMed Central

    Albuquerque Costa, Renata; Araújo, Rayza Lima; Souza, Oscarina Viana; Vieira, Regine Helena Silva dos Fernandes

    2015-01-01

    Antimicrobial susceptibility pattern was determined in 100 strains of Vibrio isolated from the Litopenaeus vannamei shrimp and identified phenotypically. A high antibiotic-resistance index (75%) was observed, with the following phenotypic profiles: monoresistance (n = 42), cross-resistance to β-lactams (n = 20) and multiple resistance (n = 13). Plasmid resistance was characterized for penicillin (n = 11), penicillin + ampicillin (n = 1), penicillin + aztreonam (n = 1), and ampicillin (n = 1). Resistance to antimicrobial drugs by the other strains (n = 86) was possibly mediated by chromosomal genes. The findings of this study support the conclusion that the cultured shrimps can be vehicles of vibrios resistant to β-lactam and tetracycline. PMID:25918714

  3. Antibiotic Cycling and Antibiotic Mixing: Which One Best Mitigates Antibiotic Resistance?

    PubMed

    Beardmore, Robert Eric; Peña-Miller, Rafael; Gori, Fabio; Iredell, Jonathan

    2017-04-01

    Can we exploit our burgeoning understanding of molecular evolution to slow the progress of drug resistance? One role of an infection clinician is exactly that: to foresee trajectories to resistance during antibiotic treatment and to hinder that evolutionary course. But can this be done at a hospital-wide scale? Clinicians and theoreticians tried to when they proposed two conflicting behavioral strategies that are expected to curb resistance evolution in the clinic, these are known as "antibiotic cycling" and "antibiotic mixing." However, the accumulated data from clinical trials, now approaching 4 million patient days of treatment, is too variable for cycling or mixing to be deemed successful. The former implements the restriction and prioritization of different antibiotics at different times in hospitals in a manner said to "cycle" between them. In antibiotic mixing, appropriate antibiotics are allocated to patients but randomly. Mixing results in no correlation, in time or across patients, in the drugs used for treatment which is why theorists saw this as an optimal behavioral strategy. So while cycling and mixing were proposed as ways of controlling evolution, we show there is good reason why clinical datasets cannot choose between them: by re-examining the theoretical literature we show prior support for the theoretical optimality of mixing was misplaced. Our analysis is consistent with a pattern emerging in data: neither cycling or mixing is a priori better than the other at mitigating selection for antibiotic resistance in the clinic.

  4. Interplay between intrinsic and acquired resistance to quinolones in Stenotrophomonas maltophilia.

    PubMed

    García-León, Guillermo; Salgado, Fabiola; Oliveros, Juan Carlos; Sánchez, María Blanca; Martínez, José Luis

    2014-05-01

    To analyse whether the mutation-driven resistance-acquisition potential of a given bacterium might be a function of its intrinsic resistome, quinolones were used as selective agents and Stenotrophomonas maltophilia was chosen as a bacterial model. S. maltophilia has two elements - SmQnr and SmeDEF - that are important in intrinsic resistance to quinolones. Using a battery of mutants in which either or both of these elements had been removed, the apparent mutation frequency for quinolone resistance and the phenotype of the selected mutants were found to be related to the intrinsic resistome and also depended on the concentration of the selector. Most mutants had phenotypes compatible with the overexpression of multidrug efflux pump(s); SmeDEF overexpression was the most common cause of quinolone resistance. Whole genome sequencing showed that mutations of the SmeRv regulator, which result in the overexpression of the efflux pump SmeVWX, are the cause of quinolone resistance in mutants not overexpressing SmeDEF. These results indicate that the development of mutation-driven antibiotic resistance is highly dependent on the intrinsic resistome, which, at least for synthetic antibiotics such as quinolones, did not develop as a response to the presence of antibiotics in the natural ecosystems in which S. maltophilia evolved.

  5. Emergence and dissemination of antibiotic resistance: a global problem.

    PubMed

    Choudhury, R; Panda, S; Singh, D V

    2012-01-01

    Antibiotic resistance is a major problem in clinical health settings. Interestingly the origin of many of antibiotic resistance mechanisms can be traced back to non-pathogenic environmental organisms. Important factors leading to the emergence and spread of antibiotic resistance include absence of regulation in the use of antibiotics, improper waste disposal and associated transmission of antibiotic resistance genes in the community through commensals. In this review, we discussed the impact of globalisation on the transmission of antibiotic resistance genes in bacteria through immigration and export/import of foodstuff. The significance of surveillance to define appropriate use of antibiotics in the clinic has been included as an important preventive measure.

  6. Resensitizing Resistant Bacteria to Antibiotics

    DTIC Science & Technology

    2011-04-01

    synergy with oxacillin against methicillin-resistant staphylococci as well as synergy with vancomycin against vancomycin -resistant staphylococci. We...then used fluorescent derivatives of the peptides to show binding to the staphylococcal surface. Finally, we conjugated one peptide (#2) to vancomycin ...through a thiol group and showed it had similar, but not better, properties than unlabeled vancomycin . Bacteriophage, Vancomycin , Phage Display

  7. Proteome studies of bacterial antibiotic resistance mechanisms.

    PubMed

    Vranakis, Iosif; Goniotakis, Ioannis; Psaroulaki, Anna; Sandalakis, Vassilios; Tselentis, Yannis; Gevaert, Kris; Tsiotis, Georgios

    2014-01-31

    Ever since antibiotics were used to help humanity battle infectious diseases, microorganisms straight away fought back. Antibiotic resistance mechanisms indeed provide microbes with possibilities to by-pass and survive the action of antibiotic drugs. Several methods have been employed to identify these microbial resistance mechanisms in an ongoing effort to reduce the steadily increasing number of treatment failures due to multi-drug-resistant microbes. Proteomics has evolved to an important tool for this area of research. Following rapid advances in whole genome sequencing, proteomic technologies have been widely used to investigate microbial gene expression. This review highlights the contribution of proteomics in identifying microbial drug resistance mechanisms. It summarizes different proteomic studies on bacteria resistant to different antibiotic drugs. The review further includes an overview of the methodologies used, as well as lists key proteins identified, thus providing the reader not only a summary of research already done, but also directions for future research. This article is part of a Special Issue entitled: Trends in Microbial Proteomics.

  8. Priorities for antibiotic resistance surveillance in Europe.

    PubMed

    Fluit, A C; van der Bruggen, J T; Aarestrup, F M; Verhoef, J; Jansen, W T M

    2006-05-01

    Antibiotic resistance is an increasing global problem. Surveillance studies are needed to monitor resistance development, to guide local empirical therapy, and to implement timely and adequate countermeasures. To achieve this, surveillance studies must have standardised methodologies, be longitudinal, and cover a sufficiently large and representative population. However, many fall short of these requirements that define good surveillance studies. Moreover, current efforts are dispersed among many, mostly small, initiatives with different objectives. These studies must be tailored to the various reservoirs of antibiotic-resistant bacteria, such as hospitalised patients, nursing homes, the community, animals and food. Two studies that could serve as examples of tailored programmes are the European Antimicrobial Resistance Surveillance System (EARSS), which collects resistance data during the diagnosis of hospitalised patients, and the DANMAP programme, which collects data in the veterinary sector. As already noted by the WHO, genetic studies that include both the typing of isolates and the characterisation of resistance determinants are necessary to understand fully the spread and development of antibiotic resistance.

  9. Chemical Countermeasures for Antibiotic Resistance

    DTIC Science & Technology

    2012-04-01

    focusing on Pseudomonas aeruginosa, methicillin resistant Staphylococcus aureus (MRSA), and MDR Acinetobacter baumannii (MDRAB); 2) re-sensitize MDR...MDR resistant strain of A. baumannii (ATCC BAA-1605) has also been investigated. The MIC of 2-AIT-2 against this strain is 200 µM, and in the presence...Analogues g–j displayed biofilm dispersal activity against A. baumannii (ATCC 19606), exhibiting EC50 values of 45-60 µM (Table 1 Supporting Data

  10. Bacterial Multidrug Efflux Pumps: Much More Than Antibiotic Resistance Determinants

    PubMed Central

    Blanco, Paula; Hernando-Amado, Sara; Reales-Calderon, Jose Antonio; Corona, Fernando; Lira, Felipe; Alcalde-Rico, Manuel; Bernardini, Alejandra; Sanchez, Maria Blanca; Martinez, Jose Luis

    2016-01-01

    Bacterial multidrug efflux pumps are antibiotic resistance determinants present in all microorganisms. With few exceptions, they are chromosomally encoded and present a conserved organization both at the genetic and at the protein levels. In addition, most, if not all, strains of a given bacterial species present the same chromosomally-encoded efflux pumps. Altogether this indicates that multidrug efflux pumps are ancient elements encoded in bacterial genomes long before the recent use of antibiotics for human and animal therapy. In this regard, it is worth mentioning that efflux pumps can extrude a wide range of substrates that include, besides antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals or bacterial metabolites, among others. In the current review, we present information on the different functions that multidrug efflux pumps may have for the bacterial behaviour in different habitats as well as on their regulation by specific signals. Since, in addition to their function in non-clinical ecosystems, multidrug efflux pumps contribute to intrinsic, acquired, and phenotypic resistance of bacterial pathogens, the review also presents information on the search for inhibitors of multidrug efflux pumps, which are currently under development, in the aim of increasing the susceptibility of bacterial pathogens to antibiotics. PMID:27681908

  11. Bacterial Multidrug Efflux Pumps: Much More Than Antibiotic Resistance Determinants.

    PubMed

    Blanco, Paula; Hernando-Amado, Sara; Reales-Calderon, Jose Antonio; Corona, Fernando; Lira, Felipe; Alcalde-Rico, Manuel; Bernardini, Alejandra; Sanchez, Maria Blanca; Martinez, Jose Luis

    2016-02-16

    Bacterial multidrug efflux pumps are antibiotic resistance determinants present in all microorganisms. With few exceptions, they are chromosomally encoded and present a conserved organization both at the genetic and at the protein levels. In addition, most, if not all, strains of a given bacterial species present the same chromosomally-encoded efflux pumps. Altogether this indicates that multidrug efflux pumps are ancient elements encoded in bacterial genomes long before the recent use of antibiotics for human and animal therapy. In this regard, it is worth mentioning that efflux pumps can extrude a wide range of substrates that include, besides antibiotics, heavy metals, organic pollutants, plant-produced compounds, quorum sensing signals or bacterial metabolites, among others. In the current review, we present information on the different functions that multidrug efflux pumps may have for the bacterial behaviour in different habitats as well as on their regulation by specific signals. Since, in addition to their function in non-clinical ecosystems, multidrug efflux pumps contribute to intrinsic, acquired, and phenotypic resistance of bacterial pathogens, the review also presents information on the search for inhibitors of multidrug efflux pumps, which are currently under development, in the aim of increasing the susceptibility of bacterial pathogens to antibiotics.

  12. Effects of temperature and antibiotics on persistence of antibiotic-resistant bacteria and antibiotic resistance genes in poultry litter

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effect of low, residual concentrations of antibiotics in manure and other environmental matrices is not well understood. It has been hypothesized that antibiotic concentrations below clinical MIC (minimal inhibitory concentrations) are still capable of selecting for resistance. The objective of ...

  13. Mass spectrometry methods for predicting antibiotic resistance.

    PubMed

    Charretier, Yannick; Schrenzel, Jacques

    2016-10-01

    Developing elaborate techniques for clinical applications can be a complicated process. Whole-cell MALDI-TOF MS revolutionized reliable microorganism identification in clinical microbiology laboratories and is now replacing phenotypic microbial identification. This technique is a generic, accurate, rapid, and cost-effective growth-based method. Antibiotic resistance keeps emerging in environmental and clinical microorganisms, leading to clinical therapeutic challenges, especially for Gram-negative bacteria. Antimicrobial susceptibility testing is used to reliably predict antimicrobial success in treating infection, but it is inherently limited by the need to isolate and grow cultures, delaying the application of appropriate therapies. Antibiotic resistance prediction by growth-independent methods is expected to reduce the turnaround time. Recently, the potential of next-generation sequencing and microarrays in predicting microbial resistance has been demonstrated, and this review evaluates the potential of MS in this field. First, technological advances are described, and the possibility of predicting antibiotic resistance by MS is then illustrated for three prototypical human pathogens: Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. Clearly, MS methods can identify antimicrobial resistance mediated by horizontal gene transfers or by mutations that affect the quantity of a gene product, whereas antimicrobial resistance mediated by target mutations remains difficult to detect.

  14. [Selection and spreading of antibiotic resistance in bacteria].

    PubMed

    Frimodt-Møller, Niels; Kolmos, Hans Jørn

    2011-11-07

    Use of an antibiotic may not only select for resistance against the agent itself, but may at the same time co-select for resistance against other antibiotics if resistance genes are linked on e.g. a plasmid. Resistance plasmids may also carry genes mediating resistance against metals and disinfectants. Therefore, abundant use of metals, e.g. copper and zinc for growth promotion in animals used for food, may also co-select for antibiotic resistance. The same applies to disinfectants, e.g. silver and chlorhexidine. Prudent use of antibiotics and these other agents is essential to control antibiotic resistance.

  15. 'Superbug' Resistant to All Antibiotics Killed Nevada Woman

    MedlinePlus

    ... gov/news/fullstory_163038.html 'Superbug' Resistant to All Antibiotics Killed Nevada Woman She died after possibly ... in September from a "superbug" infection that resisted all antibiotics, according to a report released Friday. The ...

  16. Antibiotic resistance breakers: can repurposed drugs fill the antibiotic discovery void?

    PubMed

    Brown, David

    2015-12-01

    Concern over antibiotic resistance is growing, and new classes of antibiotics, particularly against Gram-negative bacteria, are needed. However, even if the scientific hurdles can be overcome, it could take decades for sufficient numbers of such antibiotics to become available. As an interim solution, antibiotic resistance could be 'broken' by co-administering appropriate non-antibiotic drugs with failing antibiotics. Several marketed drugs that do not currently have antibacterial indications can either directly kill bacteria, reduce the antibiotic minimum inhibitory concentration when used in combination with existing antibiotics and/or modulate host defence through effects on host innate immunity, in particular by altering inflammation and autophagy. This article discusses how such 'antibiotic resistance breakers' could contribute to reducing the antibiotic resistance problem, and analyses a priority list of candidates for further investigation.

  17. Friend Turned Foe: Evolution of Enterococcal Virulence and Antibiotic Resistance

    PubMed Central

    Van Tyne, Daria; Gilmore, Michael S.

    2015-01-01

    The enterococci are an ancient genus that evolved along with the tree of life. These intrinsically rugged bacteria are highly adapted members of the intestinal consortia of a range of hosts that spans the animal kingdom. Enterococci are also leading opportunistic hospital pathogens, causing infections that are often resistant to treatment with most antibiotics. Despite the importance of enterococci as hospital pathogens, the vast majority live outside of humans, and nearly all of their evolutionary history took place before the appearance of modern humans. Because hospital infections represent evolutionary end points, traits that exacerbate human infection are unlikely to have evolved for that purpose. However, clusters of traits have converged in specific lineages that are well adapted to colonize the antibiotic-perturbed gastrointestinal tracts of patients and that thrive in the hospital environment. Here we discuss these traits in an evolutionary context, as well as how comparative genomics is providing new insights into the evolution of the enterococci. PMID:25002090

  18. Chemical Countermeasures for Antibiotic Resistance

    DTIC Science & Technology

    2015-01-01

    bacterial communication and signaling pathways, including quorum sensing and two-component signal transduction systems. Secondly we discuss enzymatic...provides a general overview of how bacteria develop into biofilm communities, why they are important, and the regulation of this process by quorum sensing ...suggesting the mode of action of oxacillin resistance suppression activity of compound 2-AIT-3 involves VraSR. The VraSR TCS in MRSA is capable of sensing

  19. Ecology and evolution of antibiotic resistance.

    PubMed

    Baquero, F; Alvarez-Ortega, C; Martinez, J L

    2009-12-01

    The evolution of bacterial pathogens towards antibiotic resistance is not just a relevant problem for human health, but a fascinating example of evolution that can be studied in real time as well. Although most antibiotics are natural compounds produced by environmental microbiota, exposure of bacterial populations to high concentrations of these compounds as the consequence of their introduction for human therapy (and later on for farming) a few decades ago is a very recent situation in evolutionary terms. Resistance genes are originated in environmental bacteria, where they have evolved for millions of years to play different functions that include detoxification, signal trafficking or metabolic functions among others. However, as the consequence of the strong selective pressure exerted by antimicrobials at clinical settings, farms and antibiotic-contaminated natural ecosystems, the selective forces driving the evolution of these potential resistance determinants have changed in the last few decades. Natural ecosystems contain a large number of potential resistance genes; nevertheless, just a few of them are currently present in gene-transfer units and disseminated among pathogens. Along the review, the processes implied in this situation and the consequences for the future evolution of resistance and the environmental microbiota are discussed.

  20. Screening and deciphering antibiotic resistance in Acinetobacter baumannii: a state of the art.

    PubMed

    Bonnin, Rémy A; Nordmann, Patrice; Poirel, Laurent

    2013-06-01

    Acinetobacter baumannii, recognized as a serious threat in healthcare facilities, has the ability to develop resistance to antibiotics quite easily. This resistance is related to either gene acquisition (horizontal gene transfer) or mutations in the genome, leading to gene disruption, over- or down-expression of genes. The clinically relevant antibiotic resistances in A. baumannii include resistance to aminoglycosides, broad-spectrum cephalosporins, carbapenems, tigecycline and colistin, which are the last resort antibiotics. The intrinsic and acquired resistance mechanisms of A. baumannii are presented here, with special focus on β-lactam resistance. The most up-to-date techniques for identification, including phenotypical and molecular tests, and screening of those emerging resistance traits are also highlighted. The implementation of early detection and identification of multidrug-resistant A. baumannii is crucial to control their spread.

  1. [The international surveillance of antibiotics resistance].

    PubMed

    Frimodt-Møller, Niels

    2011-11-07

    The growth promoter story in the 1990 s increased the focus on antibiotic misuse and related resistance. A Danish EU conference, The Microbial Threat, in 1998 resulted in The Copenhagen Recommendations, on the basic principles for a policy to contain resistance, which was transformed into EU recommendations in 2001. Following this a range of programs on monitoring of resistance and consumption, research, national campaigns etc. has been accomplished. The US, Canada and Australia have also upgraded their efforts in this area, while the WHO lacks resources to approach the countries in the rest of the world, in which these problems are the worst.

  2. Mechanisms of bacterial resistance to macrolide antibiotics.

    PubMed

    Nakajima, Yoshinori

    1999-06-01

    Macrolides have been used in the treatment of infectious diseases since the late 1950s. Since that time, a finding of antagonistic action between erythromycin and spiramycin in clinical isolates1 led to evidence of the biochemical mechanism and to the current understanding of inducible or constitutive resistance to macrolides mediated by erm genes containing, respectively, the functional regulation mechanism or constitutively mutated regulatory region. These resistant mechanisms to macrolides are recognized in clinically isolated bacteria. (1) A methylase encoded by the erm gene can transform an adenine residue at 2058 (Escherichia coli equivalent) position of 23S rRNA into an 6N, 6N-dimethyladenine. Position 2058 is known to reside either in peptidyltransferase or in the vicinity of the enzyme region of domain V. Dimethylation renders the ribosome resistant to macrolides (MLS). Moreover, another finding adduced as evidence is that a mutation in the domain plays an important role in MLS resistance: one of several mutations (transition and transversion) such as A2058G, A2058C or U, and A2059G, is usually associated with MLS resistance in a few genera of bacteria. (2) M (macrolide antibiotics)- and MS (macrolide and streptogramin type B antibiotics)- or PMS (partial macrolide and streptogramin type B antibiotics)-phenotype resistant bacteria cause decreased accumulation of macrolides, occasionally including streptogramin type B antibiotics. The decreased accumulation, probably via enhanced efflux, is usually inferred from two findings: (i) the extent of the accumulated drug in a resistant cell increases as much as that in a susceptible cell in the presence of an uncoupling agent such as carbonylcyanide-m-chlorophenylhydrazone (CCCP), 2,4-dinitrophenol (DNP), and arsenate; (ii) transporter proteins, in M-type resistants, have mutual similarity to the 12-transmembrane domain present in efflux protein driven by proton-motive force, and in MS- or PMS-type resistants

  3. Antibiotic resistance: from Darwin to Lederberg to Keynes.

    PubMed

    Amábile-Cuevas, Carlos F

    2013-04-01

    The emergence and spread of antibiotic-resistant bacteria reflects both, a gradual, completely Darwinian evolution, which mostly yields slight decreases in antibiotic susceptibility, along with phenotypes that are not precisely characterized as "resistance"; and sudden changes, from full susceptibility to full resistance, which are driven by a vast array of horizontal gene transfer mechanisms. Antibiotics select for more than just antibiotic resistance (i.e., increased virulence and enhanced gene exchange abilities); and many non-antibiotic agents or conditions select for or maintain antibiotic resistance traits as a result of a complex network of underlying and often overlapping mechanisms. Thus, the development of new antibiotics and thoughtful, integrated anti-infective strategies is needed to address the immediate and long-term threat of antibiotic resistance. Since the biology of resistance is complex, these new drugs and strategies will not come from free-market forces, or from "incentives" for pharmaceutical companies.

  4. A regulatory cascade involving AarG, a putative sensor kinase, controls the expression of the 2'-N-acetyltransferase and an intrinsic multiple antibiotic resistance (Mar) response in Providencia stuartii.

    PubMed

    Rather, P N; Paradise, M R; Parojcic, M M; Patel, S

    1998-06-01

    A recessive mutation, aarG1, has been identified that resulted in an 18-fold increase in the expression of beta-galactosidase from an aac(2')-lacZ fusion. Transcriptional fusions and Northern blot analysis demonstrated that the aarG1 allele also resulted in a large increase in the expression of aarP, a gene encoding a transcriptional activator of aac(2')-Ia. The effects of aarG1 on aac(2')-Ia expression were mediated by aarP-dependent and -independent mechanisms. The aarG1 allele also resulted in a multiple antibiotic resistance (Mar) phenotype, which included increased chloramphenicol, tetracycline and fluoroquinolone resistance. This Mar phenotype also resulted from aarP-dependent and -independent mechanisms. Sequence analysis of the aarG locus revealed the presence of two open reading frames, designated aarR and aarG, organized in tandem. The putative AarR protein displayed 75% amino acid identity to the response regulator PhoP, and the AarG protein displayed 57% amino acid identity to the sensor kinase PhoQ. The aarG1 mutation, a C to T substitution, resulted in a threonine to isoleucine substitution at position 279 (T279I) in the putative sensor kinase. The AarG product was functionally similar to PhoQ, as it was able to restore wild-type levels of maganin resistance to a Salmonella typhimurium phoQ mutant. However, expression of the aarP and aac(2')-Ia genes was not significantly affected by the levels of Mg2+ or Ca2+, suggesting that aarG senses a signal other than divalent cations.

  5. Isolated cell behavior drives the evolution of antibiotic resistance.

    PubMed

    Artemova, Tatiana; Gerardin, Ylaine; Dudley, Carmel; Vega, Nicole M; Gore, Jeff

    2015-07-29

    Bacterial antibiotic resistance is typically quantified by the minimum inhibitory concentration (MIC), which is defined as the minimal concentration of antibiotic that inhibits bacterial growth starting from a standard cell density. However, when antibiotic resistance is mediated by degradation, the collective inactivation of antibiotic by the bacterial population can cause the measured MIC to depend strongly on the initial cell density. In cases where this inoculum effect is strong, the relationship between MIC and bacterial fitness in the antibiotic is not well defined. Here, we demonstrate that the resistance of a single, isolated cell-which we call the single-cell MIC (scMIC)-provides a superior metric for quantifying antibiotic resistance. Unlike the MIC, we find that the scMIC predicts the direction of selection and also specifies the antibiotic concentration at which selection begins to favor new mutants. Understanding the cooperative nature of bacterial growth in antibiotics is therefore essential in predicting the evolution of antibiotic resistance.

  6. Assessment of Bacterial Antibiotic Resistance Transfer in the Gut

    PubMed Central

    Schjørring, Susanne; Krogfelt, Karen A.

    2011-01-01

    We assessed horizontal gene transfer between bacteria in the gastrointestinal (GI) tract. During the last decades, the emergence of antibiotic resistant strains and treatment failures of bacterial infections have increased the public awareness of antibiotic usage. The use of broad spectrum antibiotics creates a selective pressure on the bacterial flora, thus increasing the emergence of multiresistant bacteria, which results in a vicious circle of treatments and emergence of new antibiotic resistant bacteria. The human gastrointestinal tract is a massive reservoir of bacteria with a potential for both receiving and transferring antibiotic resistance genes. The increased use of fermented food products and probiotics, as food supplements and health promoting products containing massive amounts of bacteria acting as either donors and/or recipients of antibiotic resistance genes in the human GI tract, also contributes to the emergence of antibiotic resistant strains. This paper deals with the assessment of antibiotic resistance gene transfer occurring in the gut. PMID:21318188

  7. The Whys and Wherefores of Antibiotic Resistance.

    PubMed

    Strachan, Cameron R; Davies, Julian

    2017-02-01

    The development and rapid dissemination of antibiotic-resistant bacterial pathogens has tarnished the dream of a world without infectious diseases. However, our understanding of these processes, paired with sequence information from terrestrial bacterial populations, indicates that there is no shortage of novel natural products that could be developed into new medicines. Regardless, their therapeutic success in the clinic will depend on the introduction of mandatory controls and use restrictions.

  8. The world alliance against antibiotic resistance: consensus for a declaration.

    PubMed

    Carlet, Jean

    2015-06-15

    Antibiotic resistance is increasing worldwide and has become a very important threat to public health. The overconsumption of antibiotics is the most important cause of this problem. We created a World Alliance Against Antibiotic Resistance (WAAAR), which now includes 720 people from 55 different countries and is supported by 145 medical societies or various groups. In June 2014, WAAAR launched a declaration against antibiotic resistance. This article describes the process and the content of this declaration.

  9. Biofilm-specific antibiotic tolerance and resistance.

    PubMed

    Olsen, I

    2015-05-01

    Biofilms are heterogeneous structures composed of bacterial cells surrounded by a matrix and attached to solid surfaces. The bacteria here are 100 to 1,000 times more tolerant to antimicrobials than corresponding planktonic cells. Biofilms can be difficult to eradicate when they cause biofilm-related diseases, e.g., implant infections, cystic fibrosis, urinary tract infections, and periodontal diseases. A number of phenotypic features of the biofilm can be involved in biofilm-specific tolerance and resistance. Little is known about the molecular mechanisms involved. The current review deals with both phenotypic and molecular mechanisms of biofilm-specific antibiotic tolerance and resistance.

  10. Bacteriophage biosensors for antibiotic-resistant bacteria.

    PubMed

    Sorokulova, Irina; Olsen, Eric; Vodyanoy, Vitaly

    2014-03-01

    An increasing number of disease-causing bacteria are resistant to one or more anti-bacterial drugs utilized for therapy. Early and speedy detection of these pathogens is therefore very important. Traditional pathogen detection techniques, that include microbiological and biochemical assays are long and labor-intensive, while antibody or DNA-based methods require substantial sample preparation and purification. Biosensors based on bacteriophages have demonstrated remarkable potential to surmount these restrictions and to offer rapid, efficient and sensitive detection technique for antibiotic-resistant bacteria.

  11. Antibiotic resistance among Ureaplasma spp. isolates: cause for concern?

    PubMed

    Beeton, M L; Spiller, O B

    2017-02-01

    There is growing global concern regarding the rise of antibiotic-resistant organisms. Many of these reports have focused on various Gram-positive and Gram-negative pathogens, with little attention to the genus Ureaplasma. Ureaplasma spp. are associated with numerous infectious diseases affecting pregnant women, neonates and the immunocompromised. Treatment options are extremely limited due to high levels of intrinsic resistance resulting from the unique physiology of these organisms and further restricted in cases of the developing fetus or neonate, often limiting therapeutic options to predominantly macrolides or rarely fluoroquinolones. The increasing presence of macrolide- and fluoroquinolone-resistant strains among neonatal infections may result in pan-drug resistance and potentially untreatable conditions. Here, we review the requirements for accurate measurement of antimicrobial susceptibility, provide a comprehensive review of the antimicrobial resistance (AMR) for Ureaplasma species in the literature and contextualize these results relative to some investigators' reliance on commercial kits that are not CLSI compliant when determining AMR. The dramatic variation in the resistance patterns and impact of high levels of AMR amongst neonatal populations suggests the need for continued surveillance. Commercial kits represent an excellent tool for initial antibiotic susceptibility determination and screening. However, AMR reporting must utilize internationally standardized methods, as high-titre samples, or Mycoplasma hominis-contaminated samples routinely give false AMR results. Furthermore, there is a requirement for future reports to determine the underlying AMR mechanisms and determine whether expanding AMR is due to spontaneous mutation, transmission of resistance genes on mobile elements or selection and expansion of resistant clones.

  12. Fate and transport of veterinary antibiotics, antibiotic-resistant bacteria, and antibiotic resistance gene from fields receiving poultry manure during storm events

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobials are used in production agriculture to treat disease and promote animal growth, but the presence of antibiotics in the environment raises concern about widespread antibiotic resistance. This study documents the occurrence and transport of tylosin, tetracycline, enterococci resistant to...

  13. Origin and Evolution of Antibiotic Resistance: The Common Mechanisms of Emergence and Spread in Water Bodies

    PubMed Central

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

    2011-01-01

    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. PMID:22303296

  14. Antibiotrophs: The complexity of antibiotic-subsisting and antibiotic-resistant microorganisms.

    PubMed

    Woappi, Yvon; Gabani, Prashant; Singh, Arya; Singh, Om V

    2016-01-01

    Widespread overuse of antibiotics has led to the emergence of numerous antibiotic-resistant bacteria; among these are antibiotic-subsisting strains capable of surviving in environments with antibiotics as the sole carbon source. This unparalleled expansion of antibiotic resistance reveals the potent and diversified resistance abilities of certain bacterial strains. Moreover, these strains often possess hypermutator phenotypes and virulence transmissibility competent for genomic and proteomic propagation and pathogenicity. Pragmatic and prospicient approaches will be necessary to develop efficient therapeutic methods against such bacteria and to understand the extent of their genomic adaptability. This review aims to reveal the niches of these antibiotic-catabolizing microbes and assesses the underlying factors linking natural microbial antibiotic production, multidrug resistance, and antibiotic-subsistence.

  15. Addressing the Natural Antibiotic Resistome in Studies of Soil Resistance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The environment is recognized as a source and a reservoir of antibiotic resistance (AR). Many antibiotic compounds are derived from bacteria and fungi that are naturally present in the environment. These microbes carry genes encoding resistance to the antibiotic that they produce and their resistanc...

  16. Environmental dissemination of antibiotic resistance genes and correlation to anthropogenic contamination with antibiotics

    PubMed Central

    Berglund, Björn

    2015-01-01

    Antibiotic resistance is a growing problem which threatens modern healthcare globally. Resistance has traditionally been viewed as a clinical problem, but recently non-clinical environments have been highlighted as an important factor in the dissemination of antibiotic resistance genes (ARGs). Horizontal gene transfer (HGT) events are likely to be common in aquatic environments; integrons in particular are well suited for mediating environmental dissemination of ARGs. A growing body of evidence suggests that ARGs are ubiquitous in natural environments. Particularly, elevated levels of ARGs and integrons in aquatic environments are correlated to proximity to anthropogenic activities. The source of this increase is likely to be routine discharge of antibiotics and resistance genes, for example, via wastewater or run-off from livestock facilities and agriculture. While very high levels of antibiotic contamination are likely to select for resistant bacteria directly, the role of sub-inhibitory concentrations of antibiotics in environmental antibiotic resistance dissemination remains unclear. In vitro studies have shown that low levels of antibiotics can select for resistant mutants and also facilitate HGT, indicating the need for caution. Overall, it is becoming increasingly clear that the environment plays an important role in dissemination of antibiotic resistance; further studies are needed to elucidate key aspects of this process. Importantly, the levels of environmental antibiotic contamination at which resistant bacteria are selected for and HGT is facilitated at should be determined. This would enable better risk analyses and facilitate measures for preventing dissemination and development of antibiotic resistance in the environment. PMID:26356096

  17. Bacterial Cheating Limits the Evolution of Antibiotic Resistance

    NASA Astrophysics Data System (ADS)

    Yurtsev, Eugene; Xiao Chao, Hui; Datta, Manoshi; Artemova, Tatiana; Gore, Jeff

    2012-02-01

    The emergence of antibiotic resistance in bacteria is a significant health concern. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removal of the antibiotic. The presence of a cooperative mechanism of resistance suggests that a cheater strain - which does not contribute to breaking down the antibiotic - may be able to take advantage of resistant cells. We find experimentally that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We use a simple model in conjunction with difference equations to explain the observed population dynamics as a function of cell density and antibiotic concentration. Our experimental difference equations resemble the logistic map, raising the possibility of oscillations or even chaotic dynamics.

  18. Development of antibiotics and the future of marine microorganisms to stem the tide of antibiotic resistance

    PubMed Central

    Kasanah, Noer; Hamann, Mark T

    2016-01-01

    Antibiotics remain essential tools in the control of infectious diseases. With the emergence of new diseases, resistant forms of diseases such as tuberculosis and malaria, as well as the emergence of multidrug-resistant bacteria, it has become essential to develop novel antibiotics. Development of the existing antibiotics involved three strategies, including discovery of new target sites, modification of existing antibiotic structures, and the identification of new resources for novel antibiotics. Marine microorganisms have clearly become an essential new resource in the discovery of new antibiotic leads. PMID:15600239

  19. Heavy Metal Induced Antibiotic Resistance in Bacterium LSJC7.

    PubMed

    Chen, Songcan; Li, Xiaomin; Sun, Guoxin; Zhang, Yingjiao; Su, Jianqiang; Ye, Jun

    2015-09-29

    Co-contamination of antibiotics and heavy metals prevails in the environment, and may play an important role in disseminating bacterial antibiotic resistance, but the selective effects of heavy metals on bacterial antibiotic resistance is largely unclear. To investigate this, the effects of heavy metals on antibiotic resistance were studied in a genome-sequenced bacterium, LSJC7. The results showed that the presence of arsenate, copper, and zinc were implicated in fortifying the resistance of LSJC7 towards tetracycline. The concentrations of heavy metals required to induce antibiotic resistance, i.e., the minimum heavy metal concentrations (MHCs), were far below (up to 64-fold) the minimum inhibition concentrations (MIC) of LSJC7. This finding indicates that the relatively low heavy metal levels in polluted environments and in treated humans and animals might be sufficient to induce bacterial antibiotic resistance. In addition, heavy metal induced antibiotic resistance was also observed for a combination of arsenate and chloramphenicol in LSJC7, and copper/zinc and tetracycline in antibiotic susceptible strain Escherichia coli DH5α. Overall, this study implies that heavy metal induced antibiotic resistance might be ubiquitous among various microbial species and suggests that it might play a role in the emergence and spread of antibiotic resistance in metal and antibiotic co-contaminated environments.

  20. Heavy Metal Induced Antibiotic Resistance in Bacterium LSJC7

    PubMed Central

    Chen, Songcan; Li, Xiaomin; Sun, Guoxin; Zhang, Yingjiao; Su, Jianqiang; Ye, Jun

    2015-01-01

    Co-contamination of antibiotics and heavy metals prevails in the environment, and may play an important role in disseminating bacterial antibiotic resistance, but the selective effects of heavy metals on bacterial antibiotic resistance is largely unclear. To investigate this, the effects of heavy metals on antibiotic resistance were studied in a genome-sequenced bacterium, LSJC7. The results showed that the presence of arsenate, copper, and zinc were implicated in fortifying the resistance of LSJC7 towards tetracycline. The concentrations of heavy metals required to induce antibiotic resistance, i.e., the minimum heavy metal concentrations (MHCs), were far below (up to 64-fold) the minimum inhibition concentrations (MIC) of LSJC7. This finding indicates that the relatively low heavy metal levels in polluted environments and in treated humans and animals might be sufficient to induce bacterial antibiotic resistance. In addition, heavy metal induced antibiotic resistance was also observed for a combination of arsenate and chloramphenicol in LSJC7, and copper/zinc and tetracycline in antibiotic susceptible strain Escherichia coli DH5α. Overall, this study implies that heavy metal induced antibiotic resistance might be ubiquitous among various microbial species and suggests that it might play a role in the emergence and spread of antibiotic resistance in metal and antibiotic co-contaminated environments. PMID:26426011

  1. Emerging antibiotic resistance in bacteria with special reference to India.

    PubMed

    Raghunath, D

    2008-11-01

    The antibiotic era started in the 1940s and changed the profile of infectious diseases and human demography. The burgeoning classes and numbers promised much and elimination of this major cause of human (and animal) morbidity appeared possible. Bacterial antibiotic resistance which was observed soon after antibiotic introduction has been studied extensively. Diverse mechanisms have been demonstrated and the genetic basis elucidated. The resilience of the prokaryote ecosystems to antibiotic stress has been realized. The paper presents these subjects briefly to afford an overview. The epidemiology of antibiotic resistance is dealt with and community practices in different countries are described. The role of high antibiotic usage environments is indicated. The implication of the wide use of antibiotics in animals has been pointed out. Steadily increasing antibiotic resistance and decreasing numbers of newer antibiotics appear to point to a post-antibiotic period during which treatment of infections would become increasingly difficult. This article attempts to review the global antimicrobial resistance scene and juxtaposes it to the Indian experience. The prevalence in India of antibiotic resistance among major groups of pathogens is described. The factors that determine the prevalent high antibiotic resistance rates have been highlighted. The future research activity to ensure continued utility of antibiotics in the control of infections has been indicated.

  2. Antibiotic Resistance Threats in the U.S.

    MedlinePlus

    ... What's this? Submit Button Past Emails CDC Features Antibiotic Resistance Threats in the US Recommend on Facebook Tweet Share Compartir Antibiotics are powerful tools for fighting illness and disease, ...

  3. CURRENT ISSUES REGARDING ENDOCRINE DISRUPTING CHEMICALS AND ANTIBIOTIC RESISTANCE

    EPA Science Inventory

    Recently public concern has increased regarding industrial and environmental substances that may have adverse hormonal effects in human and wildlife populations. This concern has also been expanded to include antibiotic-resistant bacteria and the presence of various antibiotics a...

  4. Diversity and antibiotic resistance patterns of Sphingomonadaceae isolates from drinking water.

    PubMed

    Vaz-Moreira, Ivone; Nunes, Olga C; Manaia, Célia M

    2011-08-15

    Sphingomonadaceae (n = 86) were isolated from a drinking water treatment plant (n = 6), tap water (n = 55), cup fillers for dental chairs (n = 21), and a water demineralization filter (n = 4). The bacterial isolates were identified based on analysis of the 16S rRNA gene sequence, and intraspecies variation was assessed on the basis of atpD gene sequence analysis. The isolates were identified as members of the genera Sphingomonas (n = 27), Sphingobium (n = 28), Novosphingobium (n = 12), Sphingopyxis (n = 7), and Blastomonas (n = 12). The patterns of susceptibility to five classes of antibiotics were analyzed and compared for the different sites of isolation and taxonomic groups. Colistin resistance was observed to be intrinsic (92%). The highest antibiotic resistance prevalence values were observed in members of the genera Sphingomonas and Sphingobium and for beta-lactams, ciprofloxacin, and cotrimoxazole. In tap water and in water from dental chairs, antibiotic resistance was more prevalent than in the other samples, mainly due to the predominance of isolates of the genera Sphingomonas and Sphingobium. These two genera presented distinct patterns of association with antibiotic resistance, suggesting different paths of resistance development. Antibiotic resistance patterns were often related to the species rather than to the site or strain, suggesting the importance of vertical resistance transmission in these bacteria. This is the first study demonstrating that members of the family Sphingomonadaceae are potential reservoirs of antibiotic resistance in drinking water.

  5. Agricultural use of antibiotics and the evolution and transfer of antibiotic-resistant bacteria

    PubMed Central

    Khachatourians, G G

    1998-01-01

    Microbial Resistance to antibiotics is on the rise, in part because of inappropriate use of antibiotics in human medicine but also because of practices in the agricultural industry. Intensive animal production involves giving livestock animals large quantities of antibiotics to promote growth and prevent infection. These uses promote the selection of antibiotic resistance in bacterial populations. The resistant bacteria from agricultural environments may be transmitted to humans, in whom they cause disease that cannot be treated by conventional antibiotics. The author reviews trends in antibiotic use in animal husbandry and agriculture in general. The development of resistance is described, along with the genetic mechanisms that create resistance and facilitate its spread among bacterial species. Particular aspects of resistance in bacterial species common to both the human population and the agrifood industry are emphasized. Control measures that might reverse the current trends are highlighted. PMID:9835883

  6. Agricultural use of antibiotics and the evolution and transfer of antibiotic-resistant bacteria.

    PubMed

    Khachatourians, G G

    1998-11-03

    Microbial Resistance to antibiotics is on the rise, in part because of inappropriate use of antibiotics in human medicine but also because of practices in the agricultural industry. Intensive animal production involves giving livestock animals large quantities of antibiotics to promote growth and prevent infection. These uses promote the selection of antibiotic resistance in bacterial populations. The resistant bacteria from agricultural environments may be transmitted to humans, in whom they cause disease that cannot be treated by conventional antibiotics. The author reviews trends in antibiotic use in animal husbandry and agriculture in general. The development of resistance is described, along with the genetic mechanisms that create resistance and facilitate its spread among bacterial species. Particular aspects of resistance in bacterial species common to both the human population and the agrifood industry are emphasized. Control measures that might reverse the current trends are highlighted.

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

    PubMed

    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.

  8. Intrinsic Antimicrobial Resistance Determinants in the Superbug Pseudomonas aeruginosa

    PubMed Central

    Murray, Justine L.; Kwon, Taejoon; Marcotte, Edward M.

    2015-01-01

    ABSTRACT Antimicrobial-resistant bacteria pose a serious threat in the clinic. This is particularly true for opportunistic pathogens that possess high intrinsic resistance. Though many studies have focused on understanding the acquisition of bacterial resistance upon exposure to antimicrobials, the mechanisms controlling intrinsic resistance are not well understood. In this study, we subjected the model opportunistic superbug Pseudomonas aeruginosa to 14 antimicrobials under highly controlled conditions and assessed its response using expression- and fitness-based genomic approaches. Our results reveal that gene expression changes and mutant fitness in response to sub-MIC antimicrobials do not correlate on a genomewide scale, indicating that gene expression is not a good predictor of fitness determinants. In general, fewer fitness determinants were identified for antiseptics and disinfectants than for antibiotics. Analysis of gene expression and fitness data together allowed the prediction of antagonistic interactions between antimicrobials and insight into the molecular mechanisms controlling these interactions. PMID:26507235

  9. Fungal treatment for the removal of antibiotics and antibiotic resistance genes in veterinary hospital wastewater.

    PubMed

    Lucas, D; Badia-Fabregat, M; Vicent, T; Caminal, G; Rodríguez-Mozaz, S; Balcázar, J L; Barceló, D

    2016-06-01

    The emergence and spread of antibiotic resistance represents one of the most important public health concerns and has been linked to the widespread use of antibiotics in veterinary and human medicine. The overall elimination of antibiotics in conventional wastewater treatment plants is quite low; therefore, residual amounts of these compounds are continuously discharged to receiving surface waters, which may promote the emergence of antibiotic resistance. In this study, the ability of a fungal treatment as an alternative wastewater treatment for the elimination of forty-seven antibiotics belonging to seven different groups (β-lactams, fluoroquinolones, macrolides, metronidazoles, sulfonamides, tetracyclines, and trimethoprim) was evaluated. 77% of antibiotics were removed after the fungal treatment, which is higher than removal obtained in conventional treatment plants. Moreover, the effect of fungal treatment on the removal of some antibiotic resistance genes (ARGs) was evaluated. The fungal treatment was also efficient in removing ARGs, such as ermB (resistance to macrolides), tetW (resistance to tetracyclines), blaTEM (resistance to β-lactams), sulI (resistance to sulfonamides) and qnrS (reduced susceptibility to fluoroquinolones). However, it was not possible to establish a clear link between concentrations of antibiotics and corresponding ARGs in wastewater, which leads to the conclusion that there are other factors that should be taken into consideration besides the antibiotic concentrations that reach aquatic ecosystems in order to explain the emergence and spread of antibiotic resistance.

  10. Antibiotic resistance shaping multi-level population biology of bacteria

    PubMed Central

    Baquero, Fernando; Tedim, Ana P.; Coque, Teresa M.

    2013-01-01

    Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent “population biologies.” Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of “clinical” antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi

  11. Antibiotic resistance shaping multi-level population biology of bacteria.

    PubMed

    Baquero, Fernando; Tedim, Ana P; Coque, Teresa M

    2013-01-01

    Antibiotics have natural functions, mostly involving cell-to-cell signaling networks. The anthropogenic production of antibiotics, and its release in the microbiosphere results in a disturbance of these networks, antibiotic resistance tending to preserve its integrity. The cost of such adaptation is the emergence and dissemination of antibiotic resistance genes, and of all genetic and cellular vehicles in which these genes are located. Selection of the combinations of the different evolutionary units (genes, integrons, transposons, plasmids, cells, communities and microbiomes, hosts) is highly asymmetrical. Each unit of selection is a self-interested entity, exploiting the higher hierarchical unit for its own benefit, but in doing so the higher hierarchical unit might acquire critical traits for its spread because of the exploitation of the lower hierarchical unit. This interactive trade-off shapes the population biology of antibiotic resistance, a composed-complex array of the independent "population biologies." Antibiotics modify the abundance and the interactive field of each of these units. Antibiotics increase the number and evolvability of "clinical" antibiotic resistance genes, but probably also many other genes with different primary functions but with a resistance phenotype present in the environmental resistome. Antibiotics influence the abundance, modularity, and spread of integrons, transposons, and plasmids, mostly acting on structures present before the antibiotic era. Antibiotics enrich particular bacterial lineages and clones and contribute to local clonalization processes. Antibiotics amplify particular genetic exchange communities sharing antibiotic resistance genes and platforms within microbiomes. In particular human or animal hosts, the microbiomic composition might facilitate the interactions between evolutionary units involved in antibiotic resistance. The understanding of antibiotic resistance implies expanding our knowledge on multi

  12. Characterization of Antibiotic Resistance Genes from Lactobacillus Isolated from Traditional Dairy Products.

    PubMed

    Guo, Huiling; Pan, Lin; Li, Lina; Lu, Jie; Kwok, Laiyu; Menghe, Bilige; Zhang, Heping; Zhang, Wenyi

    2017-03-01

    Lactobacilli are widely used as starter cultures or probiotics in yoghurt, cheese, beer, wine, pickles, preserved food, and silage. They are generally recognized as safe (GRAS). However, recent studies have shown that some lactic acid bacteria (LAB) strains carry antibiotic resistance genes and are resistant to antibiotics. Some of them may even transfer their intrinsic antibiotic resistance genes to other LAB or pathogens via horizontal gene transfer, thus threatening human health. A total of 33 Lactobacillus strains was isolated from fermented milk collected from different areas of China. We analyzed (1) their levels of antibiotic resistance using a standardized dilution method, (2) their antibiotic resistance gene profiles by polymerase chain reaction (PCR) using gene-specific primers, and (3) the transferability of some of the detected resistance markers by a filter mating assay. All Lactobacillus strains were found to be resistant to vancomycin, but susceptible to gentamicin, linezolid, neomycin, erythromycin, and clindamycin. Their susceptibilities to tetracycline, kanamycin, ciprofloxacin, streptomycin, quinupristin/dalfopristin, trimethoprim, ampicillin, rifampicin, and chloramphenicol was different. Results from our PCR analysis revealed 19 vancomycin, 10 ciprofloxacin, and 1 tetracycline-resistant bacteria that carried the van(X), van(E), gyr(A), and tet(M) genes, respectively. Finally, no transferal of the monitored antibiotic resistance genes was observed in the filter mating assay. Taken together, our study generated the antibiotic resistance profiles of some milk-originated lactobacilli isolates and preliminarily assessed their risk of transferring antibiotic gene to other bacteria. The study may provide important data concerning the safe use of LAB.

  13. [Multiple antibiotic resistance of associative microflora during urogenital pathology].

    PubMed

    Akaeva, F S; Omarova, S M; Adieva, A A; Medzhidov, M M

    2008-01-01

    Susceptibility of associative microflora isolated from patients with inflammatory diseases of urogenital tract was investigated. Etiologic structure of the diseases and cross-resistance to antibiotics of Escherichia coli, Staphylococcusaureus, and Klebsiella pneumoniae strains isolated from women with endocervicitis and men with urethritiswas assessed. Ciprofloxacin and gentamycin had the highest activity, whereas beta-lactam antibiotics were mildly active. Isolated strainswere resistant to macrolides, penicillines and imipenem. Main types of multidrug resistance to antibiotics were presented in strains circulated in Dagestan.

  14. Antibiotic Resistance Is Prevalent in an Isolated Cave Microbiome

    PubMed Central

    Bhullar, Kirandeep; Waglechner, Nicholas; Pawlowski, Andrew; Koteva, Kalinka; Banks, Eric D.; Johnston, Michael D.; Barton, Hazel A.; Wright, Gerard D.

    2012-01-01

    Antibiotic resistance is a global challenge that impacts all pharmaceutically used antibiotics. The origin of the genes associated with this resistance is of significant importance to our understanding of the evolution and dissemination of antibiotic resistance in pathogens. A growing body of evidence implicates environmental organisms as reservoirs of these resistance genes; however, the role of anthropogenic use of antibiotics in the emergence of these genes is controversial. We report a screen of a sample of the culturable microbiome of Lechuguilla Cave, New Mexico, in a region of the cave that has been isolated for over 4 million years. We report that, like surface microbes, these bacteria were highly resistant to antibiotics; some strains were resistant to 14 different commercially available antibiotics. Resistance was detected to a wide range of structurally different antibiotics including daptomycin, an antibiotic of last resort in the treatment of drug resistant Gram-positive pathogens. Enzyme-mediated mechanisms of resistance were also discovered for natural and semi-synthetic macrolide antibiotics via glycosylation and through a kinase-mediated phosphorylation mechanism. Sequencing of the genome of one of the resistant bacteria identified a macrolide kinase encoding gene and characterization of its product revealed it to be related to a known family of kinases circulating in modern drug resistant pathogens. The implications of this study are significant to our understanding of the prevalence of resistance, even in microbiomes isolated from human use of antibiotics. This supports a growing understanding that antibiotic resistance is natural, ancient, and hard wired in the microbial pangenome. PMID:22509370

  15. Antibiotic-non-antibiotic combinations for combating extremely drug-resistant Gram-negative 'superbugs'.

    PubMed

    Schneider, Elena K; Reyes-Ortega, Felisa; Velkov, Tony; Li, Jian

    2017-02-28

    The emergence of antimicrobial resistance of Gram-negative pathogens has become a worldwide crisis. The status quo for combating resistance is to employ synergistic combinations of antibiotics. Faced with this fast-approaching post-antibiotic era, it is critical that we devise strategies to prolong and maximize the clinical efficacy of existing antibiotics. Unfortunately, reports of extremely drug-resistant (XDR) Gram-negative pathogens have become more common. Combining antibiotics such as polymyxin B or the broad-spectrum tetracycline and minocycline with various FDA-approved non-antibiotic drugs have emerged as a novel combination strategy against otherwise untreatable XDR pathogens. This review surveys the available literature on the potential benefits of employing antibiotic-non-antibiotic drug combination therapy. The apex of this review highlights the clinical utility of this novel therapeutic strategy for combating infections caused by 'superbugs'.

  16. Comparative Genomics of Environmental and Clinical Stenotrophomonas maltophilia Strains with Different Antibiotic Resistance Profiles

    PubMed Central

    Youenou, Benjamin; Favre-Bonté, Sabine; Bodilis, Josselin; Brothier, Elisabeth; Dubost, Audrey; Muller, Daniel; Nazaret, Sylvie

    2015-01-01

    Stenotrophomonas maltophilia, a ubiquitous Gram-negative γ-proteobacterium, has emerged as an important opportunistic pathogen responsible for nosocomial infections. A major characteristic of clinical isolates is their high intrinsic or acquired antibiotic resistance level. The aim of this study was to decipher the genetic determinism of antibiotic resistance among strains from different origins (i.e., natural environment and clinical origin) showing various antibiotic resistance profiles. To this purpose, we selected three strains isolated from soil collected in France or Burkina Faso that showed contrasting antibiotic resistance profiles. After whole-genome sequencing, the phylogenetic relationships of these 3 strains and 11 strains with available genome sequences were determined. Results showed that a strain’s phylogeny did not match their origin or antibiotic resistance profiles. Numerous antibiotic resistance coding genes and efflux pump operons were revealed by the genome analysis, with 57% of the identified genes not previously described. No major variation in the antibiotic resistance gene content was observed between strains irrespective of their origin and antibiotic resistance profiles. Although environmental strains generally carry as many multidrug resistant (MDR) efflux pumps as clinical strains, the absence of resistance–nodulation–division (RND) pumps (i.e., SmeABC) previously described to be specific to S. maltophilia was revealed in two environmental strains (BurA1 and PierC1). Furthermore the genome analysis of the environmental MDR strain BurA1 showed the absence of SmeABC but the presence of another putative MDR RND efflux pump, named EbyCAB on a genomic island probably acquired through horizontal gene transfer. PMID:26276674

  17. Sequence-Specific Targeting of Bacterial Resistance Genes Increases Antibiotic Efficacy

    PubMed Central

    Wong, Michael; Daly, Seth M.; Greenberg, David E.; Toprak, Erdal

    2016-01-01

    The lack of effective and well-tolerated therapies against antibiotic-resistant bacteria is a global public health problem leading to prolonged treatment and increased mortality. To improve the efficacy of existing antibiotic compounds, we introduce a new method for strategically inducing antibiotic hypersensitivity in pathogenic bacteria. Following the systematic verification that the AcrAB-TolC efflux system is one of the major determinants of the intrinsic antibiotic resistance levels in Escherichia coli, we have developed a short antisense oligomer designed to inhibit the expression of acrA and increase antibiotic susceptibility in E. coli. By employing this strategy, we can inhibit E. coli growth using 2- to 40-fold lower antibiotic doses, depending on the antibiotic compound utilized. The sensitizing effect of the antisense oligomer is highly specific to the targeted gene’s sequence, which is conserved in several bacterial genera, and the oligomer does not have any detectable toxicity against human cells. Finally, we demonstrate that antisense oligomers improve the efficacy of antibiotic combinations, allowing the combined use of even antagonistic antibiotic pairs that are typically not favored due to their reduced activities. PMID:27631336

  18. Can landscape ecology untangle the complexity of antibiotic resistance?

    PubMed

    Singer, Randall S; Ward, Michael P; Maldonado, George

    2006-12-01

    Bacterial resistance to antibiotics continues to pose a serious threat to human and animal health. Given the considerable spatial and temporal heterogeneity in the distribution of resistance and the factors that affect its evolution, dissemination and persistence, we argue that antibiotic resistance must be viewed as an ecological problem. A fundamental difficulty in assessing the causal relationship between antibiotic use and resistance is the confounding influence of geography: the co-localization of resistant bacterial species with antibiotic use does not necessarily imply causation and could represent the presence of environmental conditions and factors that have independently contributed to the occurrence of resistance. Here, we show how landscape ecology, which links the biotic and abiotic factors of an ecosystem, might help to untangle the complexity of antibiotic resistance and improve the interpretation of ecological studies.

  19. Bacterial Enzymes and Antibiotic Resistance- Oral Presentation

    SciTech Connect

    Maltz, Lauren

    2015-08-25

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

  20. Antibiotic resistant bacterial profiles of anaerobic swine lagoon effluent.

    PubMed

    Brooks, J P; McLaughlin, M R

    2009-01-01

    Although land application of swine (Sus scrofa) manure lagoon effluent is a common and effective method of disposal, the presence of antibiotic-resistant bacteria, both pathogenic and commensal can complicate already understood issues associated with its safe disposal. The aim of this study was to assess antibiotic resistance in swine lagoon bacteria from sow, nursery, and finisher farms in the southeastern United States. Effluents from 37 lagoons were assayed for the presence of Escherichia coli, Campylobacter, Listeria, and Salmonella. Antibiotic resistance profiles were determined by the Kirby-Bauer swab method for 12 antibiotics comprising eight classes. Statistical analyses indicated that farm type influenced the amount and type of resistance, with nurseries and sow farms ranking as most influential, perhaps due to use of more antibiotic treatments. Finisher farms tended to have the least amount of antibiotic class resistance, signaling an overall healthier market pig, and less therapeutic or prophylactic antibiotic use. Many bacterial isolates were resistant to penicillin, cephalosporin, and tetracycline class antibiotics, while nearly all were susceptible to quinolone antibiotics. It appeared that swine farm type had a significant association with the amount of resistance associated with bacterial genera sampled from the lagoons; nurseries contributed the largest amount of bacterial resistance.

  1. The relationship between pneumococcal serotypes and antibiotic resistance.

    PubMed

    Song, Jae-Hoon; Dagan, Ron; Klugman, Keith P; Fritzell, Bernard

    2012-04-05

    Streptococcus pneumoniae (SP) causes significant burden of disease, including invasive pneumococcal disease and noninvasive diseases such as pneumonia and acute otitis media. SP has at least 93 different capsular serotypes, with the various serotypes having different propensities for producing disease or developing antibiotic resistance. An increase in the prevalence of antibiotic-resistant SP serotypes has been observed globally. The objective of this paper was to examine the relationship between antibiotic resistance and SP serotypes, with a primary focus on studies published in the past 10 years. Changing trends in antibiotic resistance and serotype distribution during this time, including those before and after the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), were analyzed. Factors that influence the prevalence of antibiotic-resistant serotypes include antibiotic selection pressure, the use of PCV7, and the emergence and spread of antibiotic-resistant clones. The emergence of multidrug resistant serotype 19A is of particular concern. Antibiotic-resistant SP is a global problem that must be addressed through multiple strategies, including national vaccination programs, antibiotic control programs, and ongoing surveillance.

  2. Diverse antibiotic resistance genes in dairy cow manure.

    PubMed

    Wichmann, Fabienne; Udikovic-Kolic, Nikolina; Andrew, Sheila; Handelsman, Jo

    2014-04-22

    Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. IMPORTANCE The increasing prevalence of antibiotic resistance among bacteria is one of the most intractable challenges in 21st-century public health. The origins of resistance are complex, and a better understanding of the impacts of antibiotics used on farms would produce a more robust platform for public policy. Microbiomes of farm animals are reservoirs of antibiotic resistance genes, which may affect distribution of antibiotic resistance genes in human pathogens. Previous studies have focused on antibiotic resistance genes in manures of animals subjected

  3. A review of newly approved antibiotics and antibiotics reserved for resistant infections: Implications for emergency medicine.

    PubMed

    Mazer-Amirshahi, Maryann; Pourmand, Ali; May, Larissa

    2016-10-17

    Millions of patients are evaluated every year in the emergency department (ED) for bacterial infections. Emergency physicians often diagnose and prescribe initial antibiotic therapy for a variety of bacterial infections, ranging from simple urinary tract infections to severe sepsis. In life-threatening infections, inappropriate choice of initial antibiotic has been shown to increase morbidity and mortality. As such, initiation of appropriate antibiotic therapy on the part of the emergency physician is critical. Increasing rates of antibiotic resistance, drug allergies, and antibiotic shortages further complicates the choice of antibiotics. Patients may have a history of prior resistant infections or culture data indicating that common first-line antibiotics used in the ED may be ineffective. In recent years, there have been several new antibiotic approvals as well as renewed interest in second and third line antibiotics because of the aforementioned concerns. In addition, several newly approved antibiotics have the advantage of being administered once weekly or even as a single infusion, which has the potential to decrease hospitalizations and healthcare costs. This article reviews newly approved antibiotics and antibiotics used to treat resistant infections with a focus on implications for emergency medicine.

  4. Antibiotics Resistance in Rhizobium: Type, Process, Mechanism and Benefit for Agriculture.

    PubMed

    Naamala, Judith; Jaiswal, Sanjay K; Dakora, Felix D

    2016-06-01

    The use of high-quality rhizobial inoculants on agricultural legumes has contributed substantially to the N economy of farming systems through inputs from biological nitrogen fixation (BNF). Large populations of symbiotically effective rhizobia should be available in the rhizosphere for symbiotic BNF with host plants. The rhizobial populations should also be able to compete and infect host plants. However, the rhizosphere comprises large populations of different microorganisms. Some of these microorganisms naturally produce antibiotics which are lethal to susceptible rhizobial populations in the soil. Therefore, intrinsic resistance to antibiotics is a desirable trait for the rhizobial population. It increases the rhizobia's chances of growth, multiplication and persistence in the soil. With a large population of rhizobia in the soil, infectivity of host plants and the subsequent BNF efficiency can be guaranteed. This review, therefore, puts together findings by various researchers on antibiotic resistance in bacteria with the main emphasis on rhizobia. It describes the different modes of action of different antibiotics, the types of antibiotic resistance exhibited by rhizobia, the mechanisms of acquisition of antibiotic resistance in rhizobia and the levels of tolerance of different rhizobial species to different antibiotics.

  5. Direction of aminoacylated transfer RNAs into antibiotic synthesis and peptidoglycan-mediated antibiotic resistance.

    PubMed

    Shepherd, Jennifer; Ibba, Michael

    2013-09-17

    Prokaryotic aminoacylated-transfer RNAs often need to be efficiently segregated between translation and other cellular biosynthetic pathways. Many clinically relevant bacteria, including Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis and Pseudomonas aeruginosa direct some aminoacylated-tRNA species into peptidoglycan biosynthesis and/or membrane phospholipid modification. Subsequent indirect peptidoglycan cross-linkage or change in membrane permeability is often a prerequisite for high-level antibiotic resistance. In Streptomycetes, aminoacylated-tRNA species are used for antibiotic synthesis as well as antibiotic resistance. The direction of coding aminoacylated-tRNA molecules away from translation and into antibiotic resistance and synthesis pathways are discussed in this review.

  6. Empirical Mode Decomposition and k-Nearest Embedding Vectors for Timely Analyses of Antibiotic Resistance Trends

    PubMed Central

    Teodoro, Douglas; Lovis, Christian

    2013-01-01

    Background Antibiotic resistance is a major worldwide public health concern. In clinical settings, timely antibiotic resistance information is key for care providers as it allows appropriate targeted treatment or improved empirical treatment when the specific results of the patient are not yet available. Objective To improve antibiotic resistance trend analysis algorithms by building a novel, fully data-driven forecasting method from the combination of trend extraction and machine learning models for enhanced biosurveillance systems. Methods We investigate a robust model for extraction and forecasting of antibiotic resistance trends using a decade of microbiology data. Our method consists of breaking down the resistance time series into independent oscillatory components via the empirical mode decomposition technique. The resulting waveforms describing intrinsic resistance trends serve as the input for the forecasting algorithm. The algorithm applies the delay coordinate embedding theorem together with the k-nearest neighbor framework to project mappings from past events into the future dimension and estimate the resistance levels. Results The algorithms that decompose the resistance time series and filter out high frequency components showed statistically significant performance improvements in comparison with a benchmark random walk model. We present further qualitative use-cases of antibiotic resistance trend extraction, where empirical mode decomposition was applied to highlight the specificities of the resistance trends. Conclusion The decomposition of the raw signal was found not only to yield valuable insight into the resistance evolution, but also to produce novel models of resistance forecasters with boosted prediction performance, which could be utilized as a complementary method in the analysis of antibiotic resistance trends. PMID:23637796

  7. Cooperative Bacterial Growth Dynamics Predict the Evolution of Antibiotic Resistance

    NASA Astrophysics Data System (ADS)

    Artemova, Tatiana; Gerardin, Ylaine; Hsin-Jung Li, Sophia; Gore, Jeff

    2011-03-01

    Since the discovery of penicillin, antibiotics have been our primary weapon against bacterial infections. Unfortunately, bacteria can gain resistance to penicillin by acquiring the gene that encodes beta-lactamase, which inactivates the antibiotic. However, mutations in this gene are necessary to degrade the modern antibiotic cefotaxime. Understanding the conditions that favor the spread of these mutations is a challenge. Here we show that bacterial growth in beta-lactam antibiotics is cooperative and that the nature of this growth determines the conditions in which resistance evolves. Quantitative analysis of the growth dynamics predicts a peak in selection at very low antibiotic concentrations; competition between strains confirms this prediction. We also find significant selection at higher antibiotic concentrations, close to the minimum inhibitory concentrations of the strains. Our results argue that an understanding of the evolutionary forces that lead to antibiotic resistance requires a quantitative understanding of the evolution of cooperation in bacteria.

  8. Sensitivity of antibiotic resistant and antibiotic susceptible Escherichia coli, Enterococcus and Staphylococcus strains against ozone.

    PubMed

    Heß, Stefanie; Gallert, Claudia

    2015-12-01

    Tolerance of antibiotic susceptible and antibiotic resistant Escherichia coli, Enterococcus and Staphylococcus strains from clinical and wastewater samples against ozone was tested to investigate if ozone, a strong oxidant applied for advanced wastewater treatment, will affect the release of antibiotic resistant bacteria into the aquatic environment. For this purpose, the resistance pattern against antibiotics of the mentioned isolates and their survival after exposure to 4 mg/L ozone was determined. Antibiotic resistance (AR) of the isolates was not correlating with higher tolerance against ozone. Except for ampicillin resistant E. coli strains, which showed a trend towards increased resistance, E. coli strains that were also resistant against cotrimoxazol, ciprofloxacin or a combination of the three antibiotics were similarly or less resistant against ozone than antibiotic sensitive strains. Pigment-producing Enterococcus casseliflavus and Staphylococcus aureus seemed to be more resistant against ozone than non-pigmented species of these genera. Furthermore, aggregation or biofilm formation apparently protected bacteria in subsurface layers from inactivation by ozone. The relatively large variance of tolerance against ozone may indicate that resistance to ozone inactivation most probably depends on several factors, where AR, if at all, does not play a major role.

  9. Resistance to antibiotics in the normal flora of animals.

    PubMed

    Sørum, H; Sunde, M

    2001-01-01

    The normal bacterial flora contains antibiotic resistance genes to various degrees, even in individuals with no history of exposure to commercially prepared antibiotics. Several factors seem to increase the number of antibiotic-resistant bacteria in feces. One important factor is the exposure of the intestinal flora to antibacterial drugs. Antibiotics used as feed additives seem to play an important role in the development of antibiotic resistance in normal flora bacteria. The use of avoparcin as a feed additive has demonstrated that an antibiotic considered "safe" is responsible for increased levels of antibiotic resistance in the normal flora enterococci of animals fed with avoparcin and possibly in humans consuming products from these animals. However, other factors like stress from temperature, crowding, and management also seem to contribute to the occurrence of antibiotic resistance in normal flora bacteria. The normal flora of animals has been studied with respect to the development of antibiotic resistance over four decades, but there are few studies with the intestinal flora as the main focus. The results of earlier studies are valuable when focused against the recent understanding of mobile genetics responsible for bacterial antibiotic resistance. New studies should be undertaken to assess whether the development of antibiotic resistance in the normal flora is directly linked to the dramatic increase in antibiotic resistance of bacterial pathogens. Bacteria of the normal flora, often disregarded scientifically, should be studied with the intention of using them as active protection against infectious diseases and thereby contributing to the overall reduction of use of antibioties in both animals and humans.

  10. Antibiotic resistance genes in freshwater biofilms along a whole river.

    PubMed

    Winkworth, Cynthia L

    2013-06-01

    A key problem challenging public health officials' efforts to stem the spread of antibiotic resistance is the potential increase of resistance in the environment. Yet, despite recent and significant changes to agricultural land in New Zealand, as well as the sector's high antibiotic use, the influence on antibiotic resistance in the environment remained uncharacterised. Spatial and temporal dynamics of antibiotic resistance genes in freshwater biofilms from NZ's fourth longest river as it transitioned between low and high intensity farming were examined for 1 year. Polymerase chain reaction was employed to gauge the level of resistance present. Biofilms were screened for 10 genes conferring resistance to antibiotics used in humans only and both humans and agricultural animals. Three genes were detected, one which conferred resistance to the important human-only use antibiotic vancomycin. Detected at the two downstream sites only, and those subject to the highest combined land-use stressors, the three genes indicated an elevated presence of antibiotic resistance in relation to surrounding land use; 7.7% versus 2% across the whole river system. The detection of a gene conferring resistance to an important human-only use antibiotic was particularly concerning and highlighted human-based contamination sources along the river, in addition to those of agricultural origin.

  11. Coping with antibiotic resistance: combining nanoparticles with antibiotics and other antimicrobial agents.

    PubMed

    Allahverdiyev, Adil M; Kon, Kateryna Volodymyrivna; Abamor, Emrah Sefik; Bagirova, Malahat; Rafailovich, Miriam

    2011-11-01

    The worldwide escalation of bacterial resistance to conventional medical antibiotics is a serious concern for modern medicine. High prevalence of multidrug-resistant bacteria among bacteria-based infections decreases effectiveness of current treatments and causes thousands of deaths. New improvements in present methods and novel strategies are urgently needed to cope with this problem. Owing to their antibacterial activities, metallic nanoparticles represent an effective solution for overcoming bacterial resistance. However, metallic nanoparticles are toxic, which causes restrictions in their use. Recent studies have shown that combining nanoparticles with antibiotics not only reduces the toxicity of both agents towards human cells by decreasing the requirement for high dosages but also enhances their bactericidal properties. Combining antibiotics with nanoparticles also restores their ability to destroy bacteria that have acquired resistance to them. Furthermore, nanoparticles tagged with antibiotics have been shown to increase the concentration of antibiotics at the site of bacterium-antibiotic interaction, and to facilitate binding of antibiotics to bacteria. Likewise, combining nanoparticles with antimicrobial peptides and essential oils generates genuine synergy against bacterial resistance. In this article, we aim to summarize recent studies on interactions between nanoparticles and antibiotics, as well as other antibacterial agents to formulate new prospects for future studies. Based on the promising data that demonstrated the synergistic effects of antimicrobial agents with nanoparticles, we believe that this combination is a potential candidate for more research into treatments for antibiotic-resistant bacteria.

  12. Emergence and spread of antibiotic resistance: setting a parameter space

    PubMed Central

    Baquero, Fernando

    2014-01-01

    The emergence and spread of antibiotic resistance among human pathogens is a relevant problem for human health and one of the few evolution processes amenable to experimental studies. In the present review, we discuss some basic aspects of antibiotic resistance, including mechanisms of resistance, origin of resistance genes, and bottlenecks that modulate the acquisition and spread of antibiotic resistance among human pathogens. In addition, we analyse several parameters that modulate the evolution landscape of antibiotic resistance. Learning why some resistance mechanisms emerge but do not evolve after a first burst, whereas others can spread over the entire world very rapidly, mimicking a chain reaction, is important for predicting the evolution, and relevance for human health, of a given mechanism of resistance. Because of this, we propose that the emergence and spread of antibiotic resistance can only be understood in a multi-parameter space. Measuring the effect on antibiotic resistance of parameters such as contact rates, transfer rates, integration rates, replication rates, diversification rates, and selection rates, for different genes and organisms, growing under different conditions in distinct ecosystems, will allow for a better prediction of antibiotic resistance and possibilities of focused interventions. PMID:24678768

  13. Antibiotic Resistance of Diverse Bacteria from Aquaculture in Borneo

    PubMed Central

    Kathleen, M. M.; Felecia, C.; Reagan, E. L.; Kasing, A.; Lesley, M.; Toh, S. C.

    2016-01-01

    The administration of antimicrobials in aquaculture provides a selective pressure creating a reservoir of multiple resistant bacteria in the cultured fish and shrimps as well as the aquaculture environment. The objective of this study was to determine the extent of antibiotic resistance in aquaculture products and aquaculture's surrounding environment in Sarawak, Malaysian Borneo. Ninety-four identified bacterial isolates constituted of 17 genera were isolated from sediment, water, and cultured organisms (fish and shrimp) in selected aquaculture farms. These isolates were tested for their antibiotic resistance against 22 antibiotics from several groups using the disk diffusion method. The results show that the highest resistance was observed towards streptomycin (85%, n = 20), while the lowest resistance was towards gentamicin (1.1%, n = 90). The multiple antibiotic resistant (MAR) index of the isolates tested ranged between 0 and 0.63. It was suggested that isolates with MAR index > 0.2 were recovered from sources with high risk of antibiotic resistant contamination. This study revealed low level of antibiotic resistance in the aquaculture bacterial isolates except for streptomycin and ampicillin (>50% resistance, n = 94) which have been used in the aquaculture industry for several decades. Antibiotic resistant patterns should be continuously monitored to predict the emergence and widespread of MAR. Effective action is needed to keep the new resistance from further developing and spreading. PMID:27746817

  14. Antibiotic resistance: a primer and call to action.

    PubMed

    Smith, Rachel A; M'ikanatha, Nkuchia M; Read, Andrew F

    2015-01-01

    During the past century, discoveries of microorganisms as causes of infections and antibiotics as effective therapeutic agents have contributed to significant gains in public health in many parts of the world. Health agencies worldwide are galvanizing attention toward antibiotic resistance, which is a major threat to public health (Centers for Disease Control and Prevention, 2013; World Health Organization, 2014). Some life scientists believe that we are approaching the post-antibiotic age (Davies & Davies, 2010). The growing threat of antimicrobial resistance is fueled by complex factors with biological, behavioral, and societal aspects. This primer provides an overview of antibiotic resistance and its growing burden on public health, the biological and behavioral mechanisms that increase antibiotic resistance, and examples of where health communication scholars can contribute to efforts to make our current antibiotic drugs last as long as possible. In addition, we identify compelling challenges for current communication theories and practices.

  15. Antibiotic resistance profiles among mesophilic aerobic bacteria in Nigerian chicken litter and associated antibiotic resistance genes1.

    PubMed

    Olonitola, Olayeni Stephen; Fahrenfeld, Nicole; Pruden, Amy

    2015-05-01

    The effect of global antibiotic use practices in livestock on the emergence of antibiotic resistant pathogens is poorly understood. There is a paucity of data among African nations, which suffer from high rates of antibiotic resistant infections among the human population. Escherichia (29.5%), Staphylococcus (15.8%), and Proteus (15.79%) were the dominant bacterial genera isolated from chicken litter from four different farms in Zaria, Nigeria, all of which contain human pathogenic members. Escherichia isolates were uniformly susceptible to augmentin and cefuroxime, but resistant to sulfamethoxazole (54.5%), ampicillin (22.7%), ciprofloxacin (18.2%), cephalothin (13.6%) and gentamicin (13.6%). Staphylococcus isolates were susceptible to ciprofloxacin, gentamicin, and sulfamethoxazole, but resistant to tetracycline (86.7%), erythromycin (80%), clindamycin (60%), and penicillin (33.3%). Many of the isolates (65.4%) were resistant to multiple antibiotics, with a multiple antibiotic resistance index (MARI) ≥ 0.2. sul1, sul2, and vanA were the most commonly detected antibiotic resistance genes among the isolates. Chicken litter associated with antibiotic use and farming practices in Nigeria could be a public health concern given that the antibiotic resistant patterns among genera containing pathogens indicate the potential for antibiotic treatment failure. However, the MARI values were generally lower than reported for Escherichia coli from intensive poultry operations in industrial nations.

  16. Metagenomics and other Methods for Measuring Antibiotic Resistance in Agroecosystems

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: There is broad concern regarding antibiotic resistance on farms and in fields, however there is no standard method for defining or measuring antibiotic resistance in environmental samples. Methods: We used metagenomic, culture-based, and molecular methods to characterize the amount, t...

  17. Crystal structure of the carbapenem intrinsic resistance protein CarG.

    PubMed

    Tichy, E M; Luisi, B F; Salmond, G P C

    2014-05-01

    In the Gram-negative enterobacterium Erwinia (Pectobacterium) and Serratia sp. ATCC 39006, intrinsic resistance to the carbapenem antibiotic 1-carbapen-2-em-3-carboxylic acid is mediated by the CarF and CarG proteins, by an unknown mechanism. Here, we report a high-resolution crystal structure for the Serratia sp. ATCC 39006 carbapenem resistance protein CarG. This structure of CarG is the first in the carbapenem intrinsic resistance (CIR) family of resistance proteins from carbapenem-producing bacteria. The crystal structure shows the protein to form a homodimer, in agreement with results from analytical gel filtration. The structure of CarG does not show homology with any known antibiotic resistance proteins nor does it belong to any well-characterised protein structural family. However, it is a close structural homologue of the bacterial inhibitor of invertebrate lysozyme, PliI-Ah, with some interesting structural variations, including the absence of the catalytic site responsible for lysozyme inhibition. Both proteins show a unique β-sandwich fold with short terminal α-helices. The core of the protein is formed by stacked anti-parallel sheets that are individually very similar in the two proteins but differ in their packing interface, causing the splaying of the two sheets in CarG. Furthermore, a conserved cation binding site identified in CarG is absent from the homologue.

  18. Antibiotic resistance in the wild: an eco-evolutionary perspective.

    PubMed

    Hiltunen, Teppo; Virta, Marko; Laine, Anna-Liisa

    2017-01-19

    The legacy of the use and misuse of antibiotics in recent decades has left us with a global public health crisis: antibiotic-resistant bacteria are on the rise, making it harder to treat infections. At the same time, evolution of antibiotic resistance is probably the best-documented case of contemporary evolution. To date, research on antibiotic resistance has largely ignored the complexity of interactions that bacteria engage in. However, in natural populations, bacteria interact with other species; for example, competition and grazing are import interactions influencing bacterial population dynamics. Furthermore, antibiotic leakage to natural environments can radically alter bacterial communities. Overall, we argue that eco-evolutionary feedback loops in microbial communities can be modified by residual antibiotics and evolution of antibiotic resistance. The aim of this review is to connect some of the well-established key concepts in evolutionary biology and recent advances in the study of eco-evolutionary dynamics to research on antibiotic resistance. We also identify some key knowledge gaps related to eco-evolutionary dynamics of antibiotic resistance, and review some of the recent technical advantages in molecular microbiology that offer new opportunities for tackling these questions. Finally, we argue that using the full potential of evolutionary theory and active communication across the different fields is needed for solving this global crisis more efficiently.This article is part of the themed issue 'Human influences on evolution, and the ecological and societal consequences'.

  19. Antibiotic resistance in the wild: an eco-evolutionary perspective

    PubMed Central

    Virta, Marko

    2017-01-01

    The legacy of the use and misuse of antibiotics in recent decades has left us with a global public health crisis: antibiotic-resistant bacteria are on the rise, making it harder to treat infections. At the same time, evolution of antibiotic resistance is probably the best-documented case of contemporary evolution. To date, research on antibiotic resistance has largely ignored the complexity of interactions that bacteria engage in. However, in natural populations, bacteria interact with other species; for example, competition and grazing are import interactions influencing bacterial population dynamics. Furthermore, antibiotic leakage to natural environments can radically alter bacterial communities. Overall, we argue that eco-evolutionary feedback loops in microbial communities can be modified by residual antibiotics and evolution of antibiotic resistance. The aim of this review is to connect some of the well-established key concepts in evolutionary biology and recent advances in the study of eco-evolutionary dynamics to research on antibiotic resistance. We also identify some key knowledge gaps related to eco-evolutionary dynamics of antibiotic resistance, and review some of the recent technical advantages in molecular microbiology that offer new opportunities for tackling these questions. Finally, we argue that using the full potential of evolutionary theory and active communication across the different fields is needed for solving this global crisis more efficiently. This article is part of the themed issue ‘Human influences on evolution, and the ecological and societal consequences'. PMID:27920384

  20. Antibiotic failure mediated by a resistant subpopulation in Enterobacter cloacae.

    PubMed

    Band, Victor I; Crispell, Emily K; Napier, Brooke A; Herrera, Carmen M; Tharp, Greg K; Vavikolanu, Kranthi; Pohl, Jan; Read, Timothy D; Bosinger, Steven E; Trent, M Stephen; Burd, Eileen M; Weiss, David S

    2016-05-09

    Antibiotic resistance is a major public health threat, further complicated by unexplained treatment failures caused by bacteria that appear antibiotic susceptible. We describe an Enterobacter cloacae isolate harbouring a minor subpopulation that is highly resistant to the last-line antibiotic colistin. This subpopulation was distinct from persisters, became predominant in colistin, returned to baseline after colistin removal and was dependent on the histidine kinase PhoQ. During murine infection, but in the absence of colistin, innate immune defences led to an increased frequency of the resistant subpopulation, leading to inefficacy of subsequent colistin therapy. An isolate with a lower-frequency colistin-resistant subpopulation similarly caused treatment failure but was misclassified as susceptible by current diagnostics once cultured outside the host. These data demonstrate the ability of low-frequency bacterial subpopulations to contribute to clinically relevant antibiotic resistance, elucidating an enigmatic cause of antibiotic treatment failure and highlighting the critical need for more sensitive diagnostics.

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

    PubMed

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

    2016-03-17

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

  2. A review of global initiatives to fight antibiotic resistance and recent antibiotics׳ discovery.

    PubMed

    Chaudhary, Arpana Sagwal

    2016-11-01

    Data from across the world have shown an overall decline in the antibiotic pipeline and continually rising resistance to all first-line and last-resort antibiotics. The gaps in our knowledge of existing prevalence and mechanisms of antibiotic resistance (ABR) are all too well known. Several decades of antibiotic abuse in humans, animals, and agricultural practices have created health emergency situations and huge socio-economic impact. This paper discusses key findings of the studies conducted by several national and international collaborative organizations on the current state of affairs in ABR. Alongside, a brief overview of the antibacterial agents׳ discovery in recent years approved by the US FDA is discussed.

  3. Probing minority population of antibiotic-resistant bacteria.

    PubMed

    Huang, Tianxun; Zheng, Yan; Yan, Ya; Yang, Lingling; Yao, Yihui; Zheng, Jiaxin; Wu, Lina; Wang, Xu; Chen, Yuqing; Xing, Jinchun; Yan, Xiaomei

    2016-06-15

    The evolution and spread of antibiotic-resistant pathogens has become a major threat to public health. Advanced tools are urgently needed to quickly diagnose antibiotic-resistant infections to initiate appropriate treatment. Here we report the development of a highly sensitive flow cytometric method to probe minority population of antibiotic-resistant bacteria via single cell detection. Monoclonal antibody against TEM-1 β-lactamase and Alexa Fluor 488-conjugated secondary antibody were used to selectively label resistant bacteria green, and nucleic acid dye SYTO 62 was used to stain all the bacteria red. A laboratory-built high sensitivity flow cytometer (HSFCM) was applied to simultaneously detect the side scatter and dual-color fluorescence signals of single bacteria. By using E. coli JM109/pUC19 and E. coli JM109 as the model systems for antibiotic-resistant and antibiotic-susceptible bacteria, respectively, as low as 0.1% of antibiotic-resistant bacteria were accurately quantified. By monitoring the dynamic population change of a bacterial culture with the administration of antibiotics, we confirmed that under the antimicrobial pressure, the original low population of antibiotic-resistant bacteria outcompeted susceptible strains and became the dominant population after 5hours of growth. Detection of antibiotic-resistant infection in clinical urine samples was achieved without cultivation, and the bacterial load of susceptible and resistant strains can be faithfully quantified. Overall, the HSFCM-based quantitative method provides a powerful tool for the fundamental studies of antibiotic resistance and holds the potential to provide rapid and precise guidance in clinical therapies.

  4. The role of biofilms as environmental reservoirs of antibiotic resistance

    PubMed Central

    Balcázar, José L.; Subirats, Jéssica; Borrego, Carles M.

    2015-01-01

    Antibiotic resistance has become a significant and growing threat to public and environmental health. To face this problem both at local and global scales, a better understanding of the sources and mechanisms that contribute to the emergence and spread of antibiotic resistance is required. Recent studies demonstrate that aquatic ecosystems are reservoirs of resistant bacteria and antibiotic resistance genes as well as potential conduits for their transmission to human pathogens. Despite the wealth of information about antibiotic pollution and its effect on the aquatic microbial resistome, the contribution of environmental biofilms to the acquisition and spread of antibiotic resistance has not been fully explored in aquatic systems. Biofilms are structured multicellular communities embedded in a self-produced extracellular matrix that acts as a barrier to antibiotic diffusion. High population densities and proximity of cells in biofilms also increases the chances for genetic exchange among bacterial species converting biofilms in hot spots of antibiotic resistance. This review focuses on the potential effect of antibiotic pollution on biofilm microbial communities, with special emphasis on ecological and evolutionary processes underlying acquired resistance to these compounds. PMID:26583011

  5. Antibiotic-resistant bacteria: a challenge for the food industry.

    PubMed

    Capita, Rosa; Alonso-Calleja, Carlos

    2013-01-01

    Antibiotic-resistant bacteria were first described in the 1940s, but whereas new antibiotics were being discovered at a steady rate, the consequences of this phenomenon were slow to be appreciated. At present, the paucity of new antimicrobials coming into the market has led to the problem of antibiotic resistance fast escalating into a global health crisis. Although the selective pressure exerted by the use of antibiotics (particularly overuse or misuse) has been deemed the major factor in the emergence of bacterial resistance to these antimicrobials, concerns about the role of the food industry have been growing in recent years and have been raised at both national and international levels. The selective pressure exerted by the use of antibiotics (primary production) and biocides (e.g., disinfectants, food and feed preservatives, or decontaminants) is the main driving force behind the selection and spread of antimicrobial resistance throughout the food chain. Genetically modified (GM) crops with antibiotic resistance marker genes, microorganisms added intentionally to the food chain (probiotic or technological) with potentially transferable antimicrobial resistance genes, and food processing technologies used at sub-lethal doses (e.g., alternative non-thermal treatments) are also issues for concern. This paper presents the main trends in antibiotic resistance and antibiotic development in recent decades, as well as their economic and health consequences, current knowledge concerning the generation, dissemination, and mechanisms of antibacterial resistance, progress to date on the possible routes for emergence of resistance throughout the food chain and the role of foods as a vehicle for antibiotic-resistant bacteria. The main approaches to prevention and control of the development, selection, and spread of antibacterial resistance in the food industry are also addressed.

  6. MurAA Is Required for Intrinsic Cephalosporin Resistance of Enterococcus faecalis

    PubMed Central

    Vesić, Dušanka

    2012-01-01

    Enterococcus faecalis is a low-GC Gram-positive bacterium that is intrinsically resistant to cephalosporins, antibiotics that target cell wall biosynthesis. To probe the mechanistic basis for intrinsic resistance, a library of transposon mutants was screened to identify E. faecalis strains that are highly susceptible to ceftriaxone, revealing a transposon mutant with a disruption in murAA. murAA is predicted to encode a UDP-N-acetylglucosamine 1-carboxyvinyl transferase that catalyzes the first committed step in peptidoglycan synthesis: phosphoenolpyruvate (PEP)-dependent conversion of UDP-N-acetylglucosamine to UDP-N-acetylglucosamine-enolpyruvate. In-frame deletion of murAA, but not its homolog in the E. faecalis genome (murAB), led to increased susceptibility of E. faecalis to cephalosporins. Furthermore, expression of murAA enhanced cephalosporin resistance in an E. faecalis mutant lacking IreK (formerly PrkC), a key kinase required for cephalosporin resistance. Further genetic analysis revealed that MurAA catalytic activity is necessary but not sufficient for this role. Collectively, our data indicate that MurAA and MurAB have distinct roles in E. faecalis physiology and suggest that MurAA possesses a unique property or activity that enables it to enhance intrinsic resistance of E. faecalis to cephalosporins. PMID:22290954

  7. Eight more ways to deal with antibiotic resistance.

    PubMed

    Metz, Matthew; Shlaes, David M

    2014-08-01

    The fight against antibiotic resistance must be strengthened. We propose actions that U.S. government agencies and private sector entities can take to build a more comprehensive effort. These actions can increase the viability of investing in new antibiotics, ensure the quality and stewardship of all antibiotics, and make responses to emerging resistance more informed. Success requires the thoughtful exercise of federal authority and a firm commitment to share data and reward developers for the value generated with new, life-saving antibiotics.

  8. Eight More Ways To Deal with Antibiotic Resistance

    PubMed Central

    Shlaes, David M.

    2014-01-01

    The fight against antibiotic resistance must be strengthened. We propose actions that U.S. government agencies and private sector entities can take to build a more comprehensive effort. These actions can increase the viability of investing in new antibiotics, ensure the quality and stewardship of all antibiotics, and make responses to emerging resistance more informed. Success requires the thoughtful exercise of federal authority and a firm commitment to share data and reward developers for the value generated with new, life-saving antibiotics. PMID:24867992

  9. Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens

    PubMed Central

    Pamer, Eric G.

    2016-01-01

    The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance. These live medicines are at various stages of discovery, testing, and production and are being subjected to existing regulatory gauntlets for eventual introduction into clinical practice. The development of next-generation probiotics to reestablish colonization resistance and eliminate potential pathogens from the gut is warranted and will reduce health care–associated infections caused by highly antibiotic-resistant bacteria. PMID:27126035

  10. Resurrecting the intestinal microbiota to combat antibiotic-resistant pathogens.

    PubMed

    Pamer, Eric G

    2016-04-29

    The intestinal microbiota, which is composed of diverse populations of commensal bacterial species, provides resistance against colonization and invasion by pathogens. Antibiotic treatment can damage the intestinal microbiota and, paradoxically, increase susceptibility to infections. Reestablishing microbiota-mediated colonization resistance after antibiotic treatment could markedly reduce infections, particularly those caused by antibiotic-resistant bacteria. Ongoing studies are identifying commensal bacterial species that can be developed into next-generation probiotics to reestablish or enhance colonization resistance. These live medicines are at various stages of discovery, testing, and production and are being subjected to existing regulatory gauntlets for eventual introduction into clinical practice. The development of next-generation probiotics to reestablish colonization resistance and eliminate potential pathogens from the gut is warranted and will reduce health care-associated infections caused by highly antibiotic-resistant bacteria.

  11. Inactivation of an integrated antibiotic resistance gene in mammalian cells to re-enable antibiotic selection.

    PubMed

    Ni, Peiling; Zhang, Qian; Chen, Haixia; Chen, Lingyi

    2014-01-01

    Removing an antibiotic resistance gene allows the same antibiotic to be re-used in the next round of genetic manipulation. Here we applied the CRISPR/Cas system to disrupt the puromycin resistance gene in an engineered mouse embryonic stem cell line and then re-used puromycin selection in the resulting cells to establish stable reporter cell lines. With the CRISPR/Cas system, pre-engineered sequences, such as loxP or FRT, are not required. Thus, this technique can be used to disrupt antibiotic resistance genes that cannot be removed by the Cre-loxP and Flp-FRT systems.

  12. Antibiotics, Bacteria, and Antibiotic Resistance Genes: Aerial Transport from Cattle Feed Yards via Particulate Matter

    PubMed Central

    McEachran, Andrew D.; Blackwell, Brett R.; Hanson, J. Delton; Wooten, Kimberly J.; Mayer, Gregory D.; Cox, Stephen B.

    2015-01-01

    Background: Emergence and spread of antibiotic resistance has become a global health threat and is often linked with overuse and misuse of clinical and veterinary chemotherapeutic agents. Modern industrial-scale animal feeding operations rely extensively on veterinary pharmaceuticals, including antibiotics, to augment animal growth. Following excretion, antibiotics are transported through the environment via runoff, leaching, and land application of manure; however, airborne transport from feed yards has not been characterized. Objectives: The goal of this study was to determine the extent to which antibiotics, antibiotic resistance genes (ARG), and ruminant-associated microbes are aerially dispersed via particulate matter (PM) derived from large-scale beef cattle feed yards. Methods: PM was collected downwind and upwind of 10 beef cattle feed yards. After extraction from PM, five veterinary antibiotics were quantified via high-performance liquid chromatography with tandem mass spectrometry, ARG were quantified via targeted quantitative polymerase chain reaction, and microbial community diversity was analyzed via 16S rRNA amplification and sequencing. Results: Airborne PM derived from feed yards facilitated dispersal of several veterinary antibiotics, as well as microbial communities containing ARG. Concentrations of several antibiotics in airborne PM immediately downwind of feed yards ranged from 0.5 to 4.6 μg/g of PM. Microbial communities of PM collected downwind of feed yards were enriched with ruminant-associated taxa and were distinct when compared to upwind PM assemblages. Furthermore, genes encoding resistance to tetracycline antibiotics were significantly more abundant in PM collected downwind of feed yards as compared to upwind. Conclusions: Wind-dispersed PM from feed yards harbors antibiotics, bacteria, and ARGs. Citation: McEachran AD, Blackwell BR, Hanson JD, Wooten KJ, Mayer GD, Cox SB, Smith PN. 2015. Antibiotics, bacteria, and antibiotic

  13. Adaptive Landscapes of Resistance Genes Change as Antibiotic Concentrations Change.

    PubMed

    Mira, Portia M; Meza, Juan C; Nandipati, Anna; Barlow, Miriam

    2015-10-01

    Most studies on the evolution of antibiotic resistance are focused on selection for resistance at lethal antibiotic concentrations, which has allowed the detection of mutant strains that show strong phenotypic traits. However, solely focusing on lethal concentrations of antibiotics narrowly limits our perspective of antibiotic resistance evolution. New high-resolution competition assays have shown that resistant bacteria are selected at relatively low concentrations of antibiotics. This finding is important because sublethal concentrations of antibiotics are found widely in patients undergoing antibiotic therapies, and in nonmedical conditions such as wastewater treatment plants, and food and water used in agriculture and farming. To understand the impacts of sublethal concentrations on selection, we measured 30 adaptive landscapes for a set of TEM β-lactamases containing all combinations of the four amino acid substitutions that exist in TEM-50 for 15 β-lactam antibiotics at multiple concentrations. We found that there are many evolutionary pathways within this collection of landscapes that lead to nearly every TEM-genotype that we studied. While it is known that the pathways change depending on the type of β-lactam, this study demonstrates that the landscapes including fitness optima also change dramatically as the concentrations of antibiotics change. Based on these results we conclude that the presence of multiple concentrations of β-lactams in an environment result in many different adaptive landscapes through which pathways to nearly every genotype are available. Ultimately this may increase the diversity of genotypes in microbial populations.

  14. Plasmid interference for curing antibiotic resistance plasmids in vivo.

    PubMed

    Kamruzzaman, Muhammad; Shoma, Shereen; Thomas, Christopher M; Partridge, Sally R; Iredell, Jonathan R

    2017-01-01

    Antibiotic resistance increases the likelihood of death from infection by common pathogens such as Escherichia coli and Klebsiella pneumoniae in developed and developing countries alike. Most important modern antibiotic resistance genes spread between such species on self-transmissible (conjugative) plasmids. These plasmids are traditionally grouped on the basis of replicon incompatibility (Inc), which prevents coexistence of related plasmids in the same cell. These plasmids also use post-segregational killing ('addiction') systems, which poison any bacterial cells that lose the addictive plasmid, to guarantee their own survival. This study demonstrates that plasmid incompatibilities and addiction systems can be exploited to achieve the safe and complete eradication of antibiotic resistance from bacteria in vitro and in the mouse gut. Conjugative 'interference plasmids' were constructed by specifically deleting toxin and antibiotic resistance genes from target plasmids. These interference plasmids efficiently cured the corresponding antibiotic resistant target plasmid from different Enterobacteriaceae in vitro and restored antibiotic susceptibility in vivo to all bacterial populations into which plasmid-mediated resistance had spread. This approach might allow eradication of emergent or established populations of resistance plasmids in individuals at risk of severe sepsis, enabling subsequent use of less toxic and/or more effective antibiotics than would otherwise be possible, if sepsis develops. The generalisability of this approach and its potential applications in bioremediation of animal and environmental microbiomes should now be systematically explored.

  15. Plasmid interference for curing antibiotic resistance plasmids in vivo

    PubMed Central

    Kamruzzaman, Muhammad; Shoma, Shereen; Thomas, Christopher M.; Partridge, Sally R.

    2017-01-01

    Antibiotic resistance increases the likelihood of death from infection by common pathogens such as Escherichia coli and Klebsiella pneumoniae in developed and developing countries alike. Most important modern antibiotic resistance genes spread between such species on self-transmissible (conjugative) plasmids. These plasmids are traditionally grouped on the basis of replicon incompatibility (Inc), which prevents coexistence of related plasmids in the same cell. These plasmids also use post-segregational killing (‘addiction’) systems, which poison any bacterial cells that lose the addictive plasmid, to guarantee their own survival. This study demonstrates that plasmid incompatibilities and addiction systems can be exploited to achieve the safe and complete eradication of antibiotic resistance from bacteria in vitro and in the mouse gut. Conjugative ‘interference plasmids’ were constructed by specifically deleting toxin and antibiotic resistance genes from target plasmids. These interference plasmids efficiently cured the corresponding antibiotic resistant target plasmid from different Enterobacteriaceae in vitro and restored antibiotic susceptibility in vivo to all bacterial populations into which plasmid-mediated resistance had spread. This approach might allow eradication of emergent or established populations of resistance plasmids in individuals at risk of severe sepsis, enabling subsequent use of less toxic and/or more effective antibiotics than would otherwise be possible, if sepsis develops. The generalisability of this approach and its potential applications in bioremediation of animal and environmental microbiomes should now be systematically explored. PMID:28245276

  16. Metabolic constraints on the evolution of antibiotic resistance.

    PubMed

    Zampieri, Mattia; Enke, Tim; Chubukov, Victor; Ricci, Vito; Piddock, Laura; Sauer, Uwe

    2017-03-06

    Despite our continuous improvement in understanding antibiotic resistance, the interplay between natural selection of resistance mutations and the environment remains unclear. To investigate the role of bacterial metabolism in constraining the evolution of antibiotic resistance, we evolved Escherichia coli growing on glycolytic or gluconeogenic carbon sources to the selective pressure of three different antibiotics. Profiling more than 500 intracellular and extracellular putative metabolites in 190 evolved populations revealed that carbon and energy metabolism strongly constrained the evolutionary trajectories, both in terms of speed and mode of resistance acquisition. To interpret and explore the space of metabolome changes, we developed a novel constraint-based modeling approach using the concept of shadow prices. This analysis, together with genome resequencing of resistant populations, identified condition-dependent compensatory mechanisms of antibiotic resistance, such as the shift from respiratory to fermentative metabolism of glucose upon overexpression of efflux pumps. Moreover, metabolome-based predictions revealed emerging weaknesses in resistant strains, such as the hypersensitivity to fosfomycin of ampicillin-resistant strains. Overall, resolving metabolic adaptation throughout antibiotic-driven evolutionary trajectories opens new perspectives in the fight against emerging antibiotic resistance.

  17. Antibiotic surgical prophylaxis increases nasal carriage of antibiotic-resistant staphylococci.

    PubMed

    McMurray, Claire L; Hardy, Katherine J; Verlander, Neville Q; Hawkey, Peter M

    2015-12-01

    Staphylococci are a significant cause of hospital-acquired infection. Nasal carriage of Staphylococcus aureus is an important risk factor for infection in surgical patients and coagulase-negative staphylococci (CNS) are a major cause of prosthetic joint infections. The impact that antibiotic surgical prophylaxis has on the nasal carriage of staphylococci has not been studied. Daily nasal swabs were taken from 63 patients who received antibiotic surgical prophylaxis and 16 patients who received no antibiotics. Total aerobic bacterial count, S. aureus and CNS were enumerated by culture from nasal swabs. Representative isolates were typed by staphylococcal interspersed repeat units (SIRU) typing and PFGE, and MICs to nine antibiotics were determined. After antibiotic administration, there was a reduction in S. aureus counts (median - 2.3 log(10)c.f.u. ml(- 1)) in 64.0 % of S. aureus carriers, compared with only a 0.89 log(10)c.f.u. ml(- 1) reduction in 75.0 % of S. aureus carriers who did not receive antibiotics. A greater increase in the nasal carriage rate of meticillin-resistant CNS was observed after antibiotic surgical prophylaxis compared with hospitalization alone, with increases of 16.4 and 4.6 %, respectively. Antibiotic-resistant S. epidermidis carriage rate increased by 16.6 % after antibiotic administration compared with 7.5 % with hospitalization alone. Antibiotic surgical prophylaxis impacts the nasal carriage of both S. aureus and CNS.

  18. Evolution of antibiotic resistance by human and bacterial niche construction.

    PubMed

    Boni, Maciej F; Feldman, Marcus W

    2005-03-01

    Antibiotic treatment by humans generates strong viability selection for antibiotic-resistant bacterial strains. The frequency of host antibiotic use often determines the strength of this selection, and changing patterns of antibiotic use can generate many types of behaviors in the population dynamics of resistant and sensitive bacterial populations. In this paper, we present a simple model of hosts dimorphic for their tendency to use/avoid antibiotics and bacterial pathogens dimorphic in their resistance/sensitivity to antibiotic treatment. When a constant fraction of hosts uses antibiotics, the two bacterial strain populations can coexist unless host use-frequency is above a critical value; this critical value is derived as the ratio of the fitness cost of resistance to the fitness cost of undergoing treatment. When strain frequencies can affect host behavior, the dynamics may be analyzed in the light of niche construction. We consider three models underlying changing host behavior: conformism, the avoidance of long infections, and adherence to the advice of public health officials. In the latter two, we find that the pathogen can have quite a strong effect on host behavior. In particular, if antibiotic use is discouraged when resistance levels are high, we observe a classic niche-construction phenomenon of maintaining strain polymorphism even in parameter regions where it would not be expected.

  19. Molecular Basis of Intrinsic Macrolide Resistance in the Mycobacterium tuberculosis Complex

    PubMed Central

    Buriánková, Karolína; Doucet-Populaire, Florence; Dorson, Olivier; Gondran, Anne; Ghnassia, Jean-Claude; Weiser, Jaroslav; Pernodet, Jean-Luc

    2004-01-01

    The intrinsic resistance of the Mycobacterium tuberculosis complex (MTC) to most antibiotics, including macrolides, is generally attributed to the low permeability of the mycobacterial cell wall. However, nontuberculous mycobacteria (NTM) are much more sensitive to macrolides than members of the MTC. A search for macrolide resistance determinants within the genome of M. tuberculosis revealed the presence of a sequence encoding a putative rRNA methyltransferase. The deduced protein is similar to Erm methyltransferases, which confer macrolide-lincosamide-streptogramin (MLS) resistance by methylation of 23S rRNA, and was named ErmMT. The corresponding gene, ermMT (erm37), is present in all members of the MTC but is absent in NTM species. Part of ermMT is deleted in some vaccine strains of Mycobacterium bovis BCG, such as the Pasteur strain, which lack the RD2 region. The Pasteur strain was susceptible to MLS antibiotics, whereas MTC species harboring the RD2 region were resistant to them. The expression of ermMT in the macrolide-sensitive Mycobacterium smegmatis and BCG Pasteur conferred MLS resistance. The resistance patterns and ribosomal affinity for erythromycin of Mycobacterium host strains expressing ermMT, srmA (monomethyltransferase from Streptomyces ambofaciens), and ermE (dimethyltransferase from Saccharopolyspora erythraea) were compared, and the ones conferred by ErmMT were similar to those conferred by SrmA, corresponding to the MLS type I phenotype. These results suggest that ermMT plays a major role in the intrinsic macrolide resistance of members of the MTC and could be the first example of a gene conferring resistance by target modification in mycobacteria. PMID:14693532

  20. Molecular basis of intrinsic macrolide resistance in the Mycobacterium tuberculosis complex.

    PubMed

    Buriánková, Karolína; Doucet-Populaire, Florence; Dorson, Olivier; Gondran, Anne; Ghnassia, Jean-Claude; Weiser, Jaroslav; Pernodet, Jean-Luc

    2004-01-01

    The intrinsic resistance of the Mycobacterium tuberculosis complex (MTC) to most antibiotics, including macrolides, is generally attributed to the low permeability of the mycobacterial cell wall. However, nontuberculous mycobacteria (NTM) are much more sensitive to macrolides than members of the MTC. A search for macrolide resistance determinants within the genome of M. tuberculosis revealed the presence of a sequence encoding a putative rRNA methyltransferase. The deduced protein is similar to Erm methyltransferases, which confer macrolide-lincosamide-streptogramin (MLS) resistance by methylation of 23S rRNA, and was named ErmMT. The corresponding gene, ermMT (erm37), is present in all members of the MTC but is absent in NTM species. Part of ermMT is deleted in some vaccine strains of Mycobacterium bovis BCG, such as the Pasteur strain, which lack the RD2 region. The Pasteur strain was susceptible to MLS antibiotics, whereas MTC species harboring the RD2 region were resistant to them. The expression of ermMT in the macrolide-sensitive Mycobacterium smegmatis and BCG Pasteur conferred MLS resistance. The resistance patterns and ribosomal affinity for erythromycin of Mycobacterium host strains expressing ermMT, srmA (monomethyltransferase from Streptomyces ambofaciens), and ermE (dimethyltransferase from Saccharopolyspora erythraea) were compared, and the ones conferred by ErmMT were similar to those conferred by SrmA, corresponding to the MLS type I phenotype. These results suggest that ermMT plays a major role in the intrinsic macrolide resistance of members of the MTC and could be the first example of a gene conferring resistance by target modification in mycobacteria.

  1. Management Options for Reducing the Release of Antibiotics and Antibiotic Resistance Genes to the Environment

    PubMed Central

    Pruden, Amy; Amézquita, Alejandro; Collignon, Peter; Brandt, Kristian K.; Graham, David W.; Lazorchak, James M.; Suzuki, Satoru; Silley, Peter; Snape, Jason R.; Topp, Edward; Zhang, Tong; Zhu, Yong-Guan

    2013-01-01

    Background: There is growing concern worldwide about the role of polluted soil and water environments in the development and dissemination of antibiotic resistance. Objective: Our aim in this study was to identify management options for reducing the spread of antibiotics and antibiotic-resistance determinants via environmental pathways, with the ultimate goal of extending the useful life span of antibiotics. We also examined incentives and disincentives for action. Methods: We focused on management options with respect to limiting agricultural sources; treatment of domestic, hospital, and industrial wastewater; and aquaculture. Discussion: We identified several options, such as nutrient management, runoff control, and infrastructure upgrades. Where appropriate, a cross-section of examples from various regions of the world is provided. The importance of monitoring and validating effectiveness of management strategies is also highlighted. Finally, we describe a case study in Sweden that illustrates the critical role of communication to engage stakeholders and promote action. Conclusions: Environmental releases of antibiotics and antibiotic-resistant bacteria can in many cases be reduced at little or no cost. Some management options are synergistic with existing policies and goals. The anticipated benefit is an extended useful life span for current and future antibiotics. Although risk reductions are often difficult to quantify, the severity of accelerating worldwide morbidity and mortality rates associated with antibiotic resistance strongly indicate the need for action. PMID:23735422

  2. Integron Involvement in Environmental Spread of Antibiotic Resistance

    PubMed Central

    Stalder, Thibault; Barraud, Olivier; Casellas, Magali; Dagot, Christophe; Ploy, Marie-Cécile

    2012-01-01

    The spread of antibiotic-resistant bacteria is a growing problem and a public health issue. In recent decades, various genetic mechanisms involved in the spread of resistance genes among bacteria have been identified. Integrons – genetic elements that acquire, exchange, and express genes embedded within gene cassettes (GC) – are one of these mechanisms. Integrons are widely distributed, especially in Gram-negative bacteria; they are carried by mobile genetic elements, plasmids, and transposons, which promote their spread within bacterial communities. Initially studied mainly in the clinical setting for their involvement in antibiotic resistance, their role in the environment is now an increasing focus of attention. The aim of this review is to provide an in-depth analysis of recent studies of antibiotic-resistance integrons in the environment, highlighting their potential involvement in antibiotic-resistance outside the clinical context. We will focus particularly on the impact of human activities (agriculture, industries, wastewater treatment, etc.). PMID:22509175

  3. Essential Oils, A New Horizon in Combating Bacterial Antibiotic Resistance

    PubMed Central

    Yap, Polly Soo Xi; Yiap, Beow Chin; Ping, Hu Cai; Lim, Swee Hua Erin

    2014-01-01

    For many years, the battle between humans and the multitudes of infection and disease causing pathogens continues. Emerging at the battlefield as some of the most significant challenges to human health are bacterial resistance and its rapid rise. These have become a major concern in global public health invigorating the need for new antimicrobial compounds. A rational approach to deal with antibiotic resistance problems requires detailed knowledge of the different biological and non-biological factors that affect the rate and extent of resistance development. Combination therapy combining conventional antibiotics and essential oils is currently blooming and represents a potential area for future investigations. This new generation of phytopharmaceuticals may shed light on the development of new pharmacological regimes in combating antibiotic resistance. This review consolidated and described the observed synergistic outcome between essential oils and antibiotics, and highlighted the possibilities of essential oils as the potential resistance modifying agent. PMID:24627729

  4. Diverse Antibiotic Resistance Genes in Dairy Cow Manure

    PubMed Central

    Wichmann, Fabienne; Udikovic-Kolic, Nikolina; Andrew, Sheila; Handelsman, Jo

    2014-01-01

    ABSTRACT Application of manure from antibiotic-treated animals to crops facilitates the dissemination of antibiotic resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these antibiotic resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different antibiotic resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional antibiotic resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of antibiotic resistance genes in agriculture and clinical settings. PMID:24757214

  5. Fitness costs associated with the acquisition of antibiotic resistance.

    PubMed

    Hernando-Amado, Sara; Sanz-García, Fernando; Blanco, Paula; Martínez, José L

    2017-02-28

    Acquisition of antibiotic resistance is a relevant problem for human health. The selection and spread of antibiotic-resistant organisms not only compromise the treatment of infectious diseases, but also the implementation of different therapeutic procedures as organ transplantation, advanced surgery or chemotherapy, all of which require proficient methods for avoiding infections. It has been generally accepted that the acquisition of antibiotic resistance will produce a general metabolic burden: in the absence of selection, the resistant organisms would be outcompeted by the susceptible ones. If that was always true, discontinuation of antibiotic use would render the disappearance of resistant microorganisms. However, several studies have shown that, once resistance emerges, the recovery of a fully susceptible population even in the absence of antibiotics is not easy. In the present study, we review updated information on the effect of the acquisition of antibiotic resistance in bacterial physiology as well as on the mechanisms that allow the compensation of the fitness costs associated with the acquisition of resistance.

  6. Antibiotic Resistance of Escherichia coli Serotypes from Cochin Estuary

    PubMed Central

    Sukumaran, Divya P.; Durairaj, Srinivasan; Abdulla, Mohamed Hatha

    2012-01-01

    This study aimed at detecting the prevalence of antibiotic-resistant serotypes of Escherichia coli in Cochin estuary, India. E. coli strains were isolated during the period January 2010–December 2011 from five different stations set at Cochin estuary. Water samples from five different stations in Cochin estuary were collected on a monthly basis for a period of two years. Isolates were serotyped, antibiogram-phenotyped for twelve antimicrobial agents, and genotyped by polymerase chain reaction for uid gene that codes for β-D-glucuronidase. These E. coli strains from Cochin estuary were tested against twelve antibiotics to determine the prevalence of multiple antibiotic resistance among them. The results revealed that more than 53.33% of the isolates were multiple antibiotic resistant. Thirteen isolates showed resistance to sulphonamides and two of them contained the sul 1 gene. Class 1 integrons were detected in two E. coli strains which were resistant to more than seven antibiotics. In the present study, O serotyping, antibiotic sensitivity, and polymerase chain reaction were employed with the purpose of establishing the present distribution of multiple antibiotic-resistant serotypes, associated with E. coli isolated from different parts of Cochin estuary. PMID:23008708

  7. Antibiotic consumption and resistance: data from Europe and Germany.

    PubMed

    Meyer, Elisabeth; Gastmeier, Petra; Deja, Maria; Schwab, Frank

    2013-08-01

    The use of antibiotics - including the over- and misuse - in human and veterinary practices selected for resistant pathogens and led to their emergence and dissemination along with the transmission of resistant bacteria. The aim of this article is to prescribe the prerequisites for the surveillance of antibiotic use and bacterial resistance, to explain advantage and disadvantage of surveillance parameters used, to present new data from a surveillance network of intensive care units focusing on antibiotic use and resistance and to discuss the impact of antibiotic use on resistance. The Surveillance System of Antibiotic Use and Bacterial Resistance in Intensive Care Units (SARI) is an on-going project that collects data from its network of intensive care units (ICU) in Germany. Antimicrobial use was expressed as daily defined doses (DDD) and normalized per 1000 patient-days (pd). ICU decided either to provide monthly data on antibiotic and resistant pathogens or they decided to provide only yearly data on antibiotic use without resistance data. 85% of all antibiotics used in Germany are administered in animals; 85% of the antibiotics used in humans are prescribed in the outpatient setting and 85% of the antibiotics used in hospitals are prescribed on non-ICUs wards. The mostly widely used parameter for the surveillance of resistance is the percentage of resistant pathogens which is important to guide empirical therapy but does not measure the burden of resistance which is of interest to the public health perspective. The burden of MRSA did not increase over the last 11 years in ICUs and was 4.2MRSA/1000pd in 2011. The burden of 3rd generation resistant E. coli and K. pneumoniae more than quintupled (up to 2.6 and 1.2 respectively) and was followed by a three times increased use of carbapenems and correlated with quinolone and 3rd generation cephalosporin use. The burden VRE faecium also increased dramatically from 0.1 to 0.8 within 11 years; VRE faecium showed no

  8. Composting swine slurry to reduce indicators and antibiotic resistance genes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Over the last twenty years there have been considerable increases in the incidence of human infections with bacteria that are resistant to commonly used antibiotics. This has precipitated concerns about the use of antibiotics in livestock production. Composting of swine manure has several advantages...

  9. Bacterial cheating limits the evolution of antibiotic resistance

    NASA Astrophysics Data System (ADS)

    Chao, Hui Xiao; Datta, Manoshi; Yurtsev, Eugene; Gore, Jeff

    2011-03-01

    The widespread use of antibiotics has led to the evolution of resistance in bacteria. Bacteria can gain resistance to the antibiotic ampicillin by acquiring a plasmid carrying the gene beta-lactamase, which inactivates the antibiotic. This inactivation may represent a cooperative behavior, as the entire bacterial population benefits from removing the antibiotic. The cooperative nature of this growth suggests that a cheater strain--which does not contribute to breaking down the antibiotic--may be able to take advantage of cells cooperatively inactivating the antibiotic. Here we experimentally find that a ``sensitive'' bacterial strain lacking the plasmid conferring resistance can invade a population of resistant bacteria, even in antibiotic concentrations that should kill the sensitive strain. We observe stable coexistence between the two strains and find that a simple model successfully explains the behavior as a function of antibiotic concentration and cell density. We anticipate that our results will provide insight into the evolutionary origin of phenotypic diversity and cooperative behaviors found in nature.

  10. Evaluating antibiotic resistance genes in soils with applied manures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotics are commonly used in livestock production to promote growth and combat disease. Recent studies have shown the potential for spread of antibiotic resistance genes (ARG) to the environment following application of livestock manures. In this study, concentrations of bacteria with ARG in soi...

  11. Assessment of antibiotic resistance in runoff from cattle feedlots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of antibiotics in veterinary medicine, especially at sub-therapeutic doses, is an important issue that has captured national attention, and there is considerable concern about the potential to transmit antibiotic resistance from animals to humans via fecal contamination of surface and ground...

  12. The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria.

    PubMed

    Li, Xian-Zhi; Plésiat, Patrick; Nikaido, Hiroshi

    2015-04-01

    The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps.

  13. The Challenge of Efflux-Mediated Antibiotic Resistance in Gram-Negative Bacteria

    PubMed Central

    Plésiat, Patrick

    2015-01-01

    SUMMARY The global emergence of multidrug-resistant Gram-negative bacteria is a growing threat to antibiotic therapy. The chromosomally encoded drug efflux mechanisms that are ubiquitous in these bacteria greatly contribute to antibiotic resistance and present a major challenge for antibiotic development. Multidrug pumps, particularly those represented by the clinically relevant AcrAB-TolC and Mex pumps of the resistance-nodulation-division (RND) superfamily, not only mediate intrinsic and acquired multidrug resistance (MDR) but also are involved in other functions, including the bacterial stress response and pathogenicity. Additionally, efflux pumps interact synergistically with other resistance mechanisms (e.g., with the outer membrane permeability barrier) to increase resistance levels. Since the discovery of RND pumps in the early 1990s, remarkable scientific and technological advances have allowed for an in-depth understanding of the structural and biochemical basis, substrate profiles, molecular regulation, and inhibition of MDR pumps. However, the development of clinically useful efflux pump inhibitors and/or new antibiotics that can bypass pump effects continues to be a challenge. Plasmid-borne efflux pump genes (including those for RND pumps) have increasingly been identified. This article highlights the recent progress obtained for organisms of clinical significance, together with methodological considerations for the characterization of MDR pumps. PMID:25788514

  14. Antibiotic-Resistant Bacteria: There is Hope.

    ERIC Educational Resources Information Center

    Offner, Susan

    1998-01-01

    Argues that reduction in the use of antibiotics would enable antibiotic-sensitive bacteria to flourish. Presents an activity designed to show students how a small, seemingly unimportant difference in doubling time can, over a period of time, make an enormous difference in population size. (DDR)

  15. Are Sewage Treatment Plants Promoting Antibiotic Resistance?

    EPA Science Inventory

    1. Introduction 1.1. How bacteria exhibit resistance 1.1.1. Resistance to -lactams 1.1.2. Resistance to sulphonamides and trimethoprim 1.1.3. Resistance to macrolides 1.1.4. Resistance to fluoroquinolones 1.1.5. Resistance to tetracyclines 1.1.6. Resistance to nitroimidaz...

  16. Antibiotic Application and Emergence of Multiple Antibiotic Resistance (MAR) in Global Catfish Aquaculture.

    PubMed

    Chuah, Li-Oon; Effarizah, M E; Goni, Abatcha Mustapha; Rusul, Gulam

    2016-06-01

    Catfish is one of the most cultivated species worldwide. Antibiotics are usually used in catfish farming as therapeutic and prophylactic agents. In the USA, only oxytetracycline, a combination of sulfadimethoxine and ormetoprim, and florfenicol are approved by the Food Drug Administration for specific fish species (e.g., catfish and salmonids) and their specific diseases. Misuse of antibiotics as prophylactic agents in disease prevention, however, is common and contributes in the development of antibiotic resistance. Various studies had reported on antibiotic residues and/or resistance in farmed species, feral fish, water column, sediments, and, in a lesser content, among farm workers. Ninety percent of the world aquaculture production is carried out in developing countries, which lack regulations and enforcement on the use of antibiotics. Hence, efforts are needed to promote the development and enforcement of such a regulatory structure. Alternatives to antibiotics such as antibacterial vaccines, bacteriophages and their lysins, and probiotics have been applied to curtail the increasing emergence of antibiotic-resistant bacteria due to the imprudent application of antibiotics in aquaculture.

  17. Modes and Modulations of Antibiotic Resistance Gene Expression

    PubMed Central

    Depardieu, Florence; Podglajen, Isabelle; Leclercq, Roland; Collatz, Ekkehard; Courvalin, Patrice

    2007-01-01

    Since antibiotic resistance usually affords a gain of function, there is an associated biological cost resulting in a loss of fitness of the bacterial host. Considering that antibiotic resistance is most often only transiently advantageous to bacteria, an efficient and elegant way for them to escape the lethal action of drugs is the alteration of resistance gene expression. It appears that expression of bacterial resistance to antibiotics is frequently regulated, which indicates that modulation of gene expression probably reflects a good compromise between energy saving and adjustment to a rapidly evolving environment. Modulation of gene expression can occur at the transcriptional or translational level following mutations or the movement of mobile genetic elements and may involve induction by the antibiotic. In the latter case, the antibiotic can have a triple activity: as an antibacterial agent, as an inducer of resistance to itself, and as an inducer of the dissemination of resistance determinants. We will review certain mechanisms, all reversible, that bacteria have elaborated to achieve antibiotic resistance by the fine-tuning of the expression of genetic information. PMID:17223624

  18. [Effect of Three Typical Disinfection Byproducts on Bacterial Antibiotic Resistance].

    PubMed

    Lü, Lu; Zhang, Meng-lu; Wang, Chun-ming; Lin, Hui-rong; Yu, Xin

    2015-07-01

    The effect of typical disinfection byproducts (DBPs) on bacterial antibiotic resistance was investigated in this study. chlorodibromomethane (CDBM), iodoacetic acid (IAA) and chloral hydrate (CH) were selected, which belong to trihalomethanes (THMs), haloacetic acids (HAAs) and aldehydes, respectively. After exposure to the selected DBPs, the resistance change of the tested strains to antibiotics was determined. As a result, all of the three DBPs induced Pseudomonas aeruginosa PAO1 to gain increased resistance to the five antibiotics tested, and the DBPs ranked as IAA > CH > CDBM according to their enhancement effects. Multidrug resistance could also be enhanced by treatment with IAA. The same result was observed in Escherichia coli K12, suggesting that the effect of DBPs on antibiotic resistance was a common phenomenon. The mechanism was probably that DBPs stimulated oxidative stress, which induced mutagenesis. And the antibiotic resistance mutation frequency could be increased along with mutagenesis. This study revealed that the acquisition of bacterial antibiotic resistance might be related to DBPs in drinking water systems. Besides the genotoxicological risks, the epidemiological risks of DBPs should not be overlooked.

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

    PubMed

    Xia, Jufeng; Gao, Jianjun; Tang, Wei

    2016-02-01

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

  20. Assessing antibiotic resistance of microorganisms in sanitary sewage.

    PubMed

    Kaeseberg, Thomas; Blumensaat, Frank; Zhang, Jin; Krebs, Peter

    2015-01-01

    The release of antimicrobial substances into surface waters is of growing concern due to direct toxic effects on all trophic levels and the promotion of antibiotic resistance through sub-inhibitory concentration levels. This study showcases (1) the variation of antibiotics in sanitary sewage depending on different timescales and (2) a method to assess the antibiotic resistance based on an inhibition test. The test is based on the measurement of the oxygen uptake rate (OUR) in wastewater samples with increasing concentrations of the selected antibiotic agents. The following antibiotics were analysed in the present study: clarithromycin (CLA) was selected due to its high toxicity to many microorganisms (low EC50), ciprofloxacin (CIP) which is used to generally fight all bacteria concerning interstitial infections and doxycyclin (DOX) having a broad spectrum efficacy. Results show that CLA inhibited the OUR by approximately 50% at a concentration of about 10 mg L⁻¹, because Gram-negative bacteria such as Escherichia coli are resistant, whereas CIP inhibited about 90% of the OUR at a concentration equal to or greater than 10 mg L⁻¹. In the case of DOX, a moderate inhibition of about 38% at a concentration of 10 mg L⁻¹ was identified, indicating a significant antibiotic resistance. The results are consistent with the corresponding findings from the Clinical and Laboratory Standards Institute. Thus, the presented inhibition test provides a simple but robust alternative method to assess antibiotic resistance in biofilms instead of more complex clinical tests.

  1. Prevalence of antibiotic-resistant bacteria in herbal products.

    PubMed

    Brown, Joseph C; Jiang, Xiuping

    2008-07-01

    The objective of this study was to determine the prevalence of antibiotic-resistant bacteria in various herbal products. Twenty-nine herbal supplements (18 traditional and 11 organic products) were purchased from stores and analyzed microbiologically. Total bacterial counts were determined by pour plate and surface spreading on tryptic soy agar (TSA). Antibiotic-resistant bacteria were enumerated on TSA supplemented with ceftriaxone (64 microg/ml) or tetracycline (16 microg/ml). Total bacterial counts ranged from <5 to 2.9 x 10(5) CFU/g. Ceftriaxone- and tetracycline-resistant bacteria were detected in ground garlic samples at 1.1 x 10(2) CFU/g and 3.0 x 102 CFU/g, respectively. Traditional and organic onion powder samples contained tetracycline-resistant bacteria at 17 and 28 CFU/g and ceftriaxone-resistant bacteria at 35 and 2.0 x 10(3) CFU/g, respectively. Other products such as ginger, rosemary, mustard, and goldenseal contained low levels of resistant bacteria. Fifty-two isolates were further evaluated against nine antibiotics, and the prevalence of antibiotic resistance was in the following order: ampicillin, nalidixic acid, trimethoprim, ceftriaxone, and streptomycin. Resistant bacteria were identified as Bacillus spp., Erwinia spp., and Ewingella americana. Staphylococcus spp., Enterobacter cloacae, and Stenotrophomonas maltophilia also were isolated. The presence of antibiotic-resistant bacteria and pathogens in these herbal products suggests that production and use of these products may need further evaluation.

  2. Targets for Combating the Evolution of Acquired Antibiotic Resistance.

    PubMed

    Culyba, Matthew J; Mo, Charlie Y; Kohli, Rahul M

    2015-06-16

    Bacteria possess a remarkable ability to rapidly adapt and evolve in response to antibiotics. Acquired antibiotic resistance can arise by multiple mechanisms but commonly involves altering the target site of the drug, enzymatically inactivating the drug, or preventing the drug from accessing its target. These mechanisms involve new genetic changes in the pathogen leading to heritable resistance. This recognition underscores the importance of understanding how such genetic changes can arise. Here, we review recent advances in our understanding of the processes that contribute to the evolution of antibiotic resistance, with a particular focus on hypermutation mediated by the SOS pathway and horizontal gene transfer. We explore the molecular mechanisms involved in acquired resistance and discuss their viability as potential targets. We propose that additional studies into these adaptive mechanisms not only can provide insights into evolution but also can offer a strategy for potentiating our current antibiotic arsenal.

  3. Antibiotic Resistance: The Need For a Global Strategy.

    PubMed

    Elder, David P; Kuentz, Martin; Holm, René

    2016-08-01

    The development of antibiotic resistance is a major problem for mankind and results in fatal consequences on a daily basis across the globe. There are a number of reasons for this situation including increasing globalization with worldwide travel, health tourism, over use and ineffective use (both in man and animals), and counterfeiting of the antimicrobial drug products we have available currently. Although there are huge economical, demographic, legal and logistic differences among the global communities, there are also differences regarding the best approach to dealing with antibiotic resistance. However, as resistant bacteria do not respect international borders, there is clearly a need for a global strategy to minimize the spread of antibiotic resistance, to optimize the use of antibiotics, and to facilitate the development of new and effective medications. This commentary provides an insight into the issues and some of the ongoing programs to ensure an effective treatment for the future.

  4. Bacterial antibiotic resistance in soils irrigated with reclaimed municipal wastewater

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wastewater reclamation for municipal irrigation and groundwater recharge is an increasingly attractive option for extending water supplies. However, public health concerns include the potential for development of antibiotic resistance (AR) in soil bacteria after exposure to residual chemicals in rec...

  5. Targets for Combating the Evolution of Acquired Antibiotic Resistance

    PubMed Central

    2015-01-01

    Bacteria possess a remarkable ability to rapidly adapt and evolve in response to antibiotics. Acquired antibiotic resistance can arise by multiple mechanisms but commonly involves altering the target site of the drug, enzymatically inactivating the drug, or preventing the drug from accessing its target. These mechanisms involve new genetic changes in the pathogen leading to heritable resistance. This recognition underscores the importance of understanding how such genetic changes can arise. Here, we review recent advances in our understanding of the processes that contribute to the evolution of antibiotic resistance, with a particular focus on hypermutation mediated by the SOS pathway and horizontal gene transfer. We explore the molecular mechanisms involved in acquired resistance and discuss their viability as potential targets. We propose that additional studies into these adaptive mechanisms not only can provide insights into evolution but also can offer a strategy for potentiating our current antibiotic arsenal. PMID:26016604

  6. Chloroquinolines block antibiotic efflux pumps in antibiotic-resistant Enterobacter aerogenes isolates.

    PubMed

    Ghisalberti, Didier; Mahamoud, Abdallah; Chevalier, Jacqueline; Baitiche, Milad; Martino, Michèle; Pagès, Jean-Marie; Barbe, Jacques

    2006-06-01

    Efflux mechanisms protect bacterial cells by pumping out toxic compounds and actively contribute to bacterial multidrug resistance. Agents inhibiting efflux pumps are of interest for the control of multidrug-resistant bacterial infections. Herein we report the effects of new chloroquinoline derivatives that render resistant Enterobacter aerogenes isolates noticeably more susceptible to structurally unrelated antibiotics. In addition, some of these chloroquinolines increase the intracellular concentration of chloramphenicol. Some of the molecules tested in this work are able to inhibit the main efflux pump (AcrAB-TolC), which is involved in E. aerogenes antibiotic resistance.

  7. Rapid methods for detection of bacterial resistance to antibiotics.

    PubMed

    March-Rosselló, Gabriel Alberto

    2017-03-01

    The most widely used antibiotic susceptibility testing methods in Clinical Microbiology are based on the phenotypic detection of antibiotic resistance by measuring bacterial growth in the presence of the antibiotic being tested. These conventional methods take typically 24hours to obtain results. Here we review the main techniques for rapid determination of antibiotic susceptibility. Data obtained with different methods such as molecular techniques, microarrays, commercial methods used in work routine, immunochromatographic methods, colorimetric methods, image methods, nephelometry, MALDI-TOF mass spectrometry, flow cytometry, chemiluminescence and bioluminescence, microfluids and methods based on cell disruption are analysed in detail.

  8. Antibiotic resistance among Helicobacter pylori clinical isolates in Lima, Peru

    PubMed Central

    Boehnke, Kevin F; Valdivieso, Manuel; Bussalleu, Alejandro; Sexton, Rachael; Thompson, Kathryn C; Osorio, Soledad; Reyes, Italo Novoa; Crowley, John J; Baker, Laurence H; Xi, Chuanwu

    2017-01-01

    Objectives Gastric carcinoma is the most common cancer and cause of cancer mortality in Peru. Helicobacter pylori, a bacterium that colonizes the human stomach, is a Group 1 carcinogen due to its causal relationship to gastric carcinoma. While eradication of H. pylori can help prevent gastric cancer, characterizing regional antibiotic resistance patterns is necessary to determine targeted treatment for each region. Thus, we examined primary antibiotic resistance in clinical isolates of H. pylori in Lima, Peru. Materials and methods H. pylori strains were isolated from gastric biopsies of patients with histologically proven H. pylori infection. Primary antibiotic resistance among isolates was examined using E-test strips. Isolates were examined for the presence of the cagA pathogenicity island and the vacA m1/m2 alleles via polymerase chain reaction. Results Seventy-six isolates were recovered from gastric biopsies. Clinical isolates showed evidence of antibiotic resistance to 1 (27.6%, n=21/76), 2 (28.9%, n=22/76), or ≥3 antibiotics (40.8%). Of 76 isolates, eight (10.5%) were resistant to amoxicillin and clarithromycin, which are part of the standard triple therapy for H. pylori infection. No trends were seen between the presence of cagA, vacA m1, or vacA m2 and antibiotic resistance. Conclusion The rate of antibiotic resistance among H. pylori isolates in Lima, Peru, is higher than expected and presents cause for concern. To develop more targeted eradication therapies for H. pylori in Peru, more research is needed to better characterize antibiotic resistance among a larger number of clinical isolates prospectively. PMID:28331349

  9. Antibiotic resistance in Enterobacteriaceae: what impact on the efficacy of antibiotic prophylaxis in colorectal surgery?

    PubMed

    Kirby, A; Santoni, N

    2015-04-01

    Antibiotic prophylaxis, introduced in the 1940s, brought in an era of relatively safe colorectal surgery. This was achieved in part due to the prevention of surgical site infections (SSIs) caused by Enterobacteriaceae. Since then, Enterobacteriaceae have become increasingly resistant to the antibiotics commonly used for prophylaxis. The impact of being colonized preoperatively with resistant Enterobacteriaceae on the efficacy of colorectal SSI prophylaxis, if any, is unknown. It is also difficult to predict the likely impact of resistance as the exposure‒response relationships have not been determined for antibiotic surgical prophylaxis. Neither is it known which test for resistance to use; the importance of the concentration of Enterobacteriaceae in the colon, the ability of different species of Enterobacteriaceae to cause SSIs, and the comparative ability of minimum inhibitory concentration or presence of a resistance mechanism in predicting SSI risk have yet to be established. Clinical research is urgently needed to answer these questions.

  10. A systematic review and meta-analysis of the effects of antibiotic consumption on antibiotic resistance

    PubMed Central

    2014-01-01

    Background Greater use of antibiotics during the past 50 years has exerted selective pressure on susceptible bacteria and may have favoured the survival of resistant strains. Existing information on antibiotic resistance patterns from pathogens circulating among community-based patients is substantially less than from hospitalized patients on whom guidelines are often based. We therefore chose to assess the relationship between the antibiotic resistance pattern of bacteria circulating in the community and the consumption of antibiotics in the community. Methods Both gray literature and published scientific literature in English and other European languages was examined. Multiple regression analysis was used to analyse whether studies found a positive relationship between antibiotic consumption and resistance. A subsequent meta-analysis and meta-regression was conducted for studies for which a common effect size measure (odds ratio) could be calculated. Results Electronic searches identified 974 studies but only 243 studies were considered eligible for inclusion by the two independent reviewers who extracted the data. A binomial test revealed a positive relationship between antibiotic consumption and resistance (p < .001) but multiple regression modelling did not produce any significant predictors of study outcome. The meta-analysis generated a significant pooled odds ratio of 2.3 (95% confidence interval 2.2 to 2.5) with a meta-regression producing several significant predictors (F(10,77) = 5.82, p < .01). Countries in southern Europe produced a stronger link between consumption and resistance than other regions. Conclusions Using a large set of studies we found that antibiotic consumption is associated with the development of antibiotic resistance. A subsequent meta-analysis, with a subsample of the studies, generated several significant predictors. Countries in southern Europe produced a stronger link between consumption and resistance than other

  11. [Update on antibiotic resistance in Gram-positive bacteria].

    PubMed

    Lozano, Carmen; Torres, Carmen

    2017-01-01

    Antimicrobial resistance among Gram-positive bacteria, especially in Staphylococcus aureus, Enterococcus faecium, Enterococcus faecalis, and Streptococcus pneumoniae, is a serious threat to public health. These microorganisms have multiple resistance mechanisms to agents currently used in clinical practice. Many of these resistance mechanisms are common to all 4 of these bacterial species, but other mechanisms seem to be more specific. The prevalence and dissemination of these mechanisms varies considerably, depending on the microorganism. This review discusses the resistance mechanisms to the most clinically relevant antibiotics, with particular emphasis on the new mechanisms described for widely used antibiotics and for newer agents such as lipopeptides, lipoglycopeptides, glycylcyclines and oxazolidinones.

  12. Co-occurrence of antibiotic drugs, resistant bacteria and resistance genes in runoff from cattle feedlots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agricultural uses of antibiotics raises concerns about the development of antibiotic resistance in food animals, and the potential to transmit resistance to human clinical settings via fecal contamination of surface and ground water. Although there is broad agreement that agricultural resistance can...

  13. Contribution of Resistance-Nodulation-Cell Division Efflux Systems to Antibiotic Resistance and Biofilm Formation in Acinetobacter baumannii

    PubMed Central

    Yoon, Eun-Jeong; Nait Chabane, Yassine; Goussard, Sylvie; Snesrud, Erik; Courvalin, Patrice; Dé, Emmanuelle

    2015-01-01

    ABSTRACT Acinetobacter baumannii is a nosocomial pathogen of increasing importance due to its multiple resistance to antibiotics and ability to survive in the hospital environment linked to its capacity to form biofilms. To fully characterize the contribution of AdeABC, AdeFGH, and AdeIJK resistance-nodulation-cell division (RND)-type efflux systems to acquired and intrinsic resistance, we constructed, from an entirely sequenced susceptible A. baumannii strain, a set of isogenic mutants overexpressing each system following introduction of a point mutation in their cognate regulator or a deletion for the pump by allelic replacement. Pairwise comparison of every derivative with the parental strain indicated that AdeABC and AdeFGH are tightly regulated and contribute to acquisition of antibiotic resistance when overproduced. AdeABC had a broad substrate range, including β-lactams, fluoroquinolones, tetracyclines-tigecycline, macrolides-lincosamides, and chloramphenicol, and conferred clinical resistance to aminoglycosides. Importantly, when combined with enzymatic resistance to carbapenems and aminoglycosides, this pump contributed in a synergistic fashion to the level of resistance of the host. In contrast, AdeIJK was expressed constitutively and was responsible for intrinsic resistance to the same major drug classes as AdeABC as well as antifolates and fusidic acid. Surprisingly, overproduction of AdeABC and AdeIJK altered bacterial membrane composition, resulting in decreased biofilm formation but not motility. Natural transformation and plasmid transfer were diminished in recipients overproducing AdeABC. It thus appears that alteration in the expression of efflux systems leads to multiple changes in the relationship between the host and its environment, in addition to antibiotic resistance. PMID:25805730

  14. Indirect Selection for Antibiotic Resistance in Multiple Stream Microhabitats

    NASA Astrophysics Data System (ADS)

    Wright, M. S.; Peltier, G. L.; McArthur, J.

    2005-05-01

    One aspect challenging public health efforts to minimize the spread of antibiotic resistance (AR) is the prevalence of resistant bacteria in the environment. Anthropogenic-derived sources of selection are typically implicated as mechanisms for maintaining AR in the environment. Here we report an additional mechanism for maintaining AR in the environment through co- or cross-resistance to heavy metals. Using culture-independent techniques, bacteria isolated from heavy-metal contaminated sites were more tolerant of antibiotics and metals compared to those bacteria from a reference site. This evidence supports our hypothesis that metal contamination directly selects for metal tolerant bacteria while indirectly selecting for antibiotic tolerant bacteria. Additionally, to assess how antibiotic- and metal-tolerance may be transported through a stream network, we studied antibiotic and metal-tolerance patterns over four months in bacteria collected from multiple stream microhabitats including water column, biofilm, sediment, and Corbicula fluminea (Asiatic clam) digestive tracts. Sediment bacteria were the most tolerant to antibiotics and metals, while bacteria from Corbicula were the least tolerant. Differences between these microhabitats may be important for predicting antibiotic resistance transfer and transport in stream environments. Further, temporal dynamics suggest that tolerance patterns within microhabitats are linked to physico-chemical characteristics of the stream.

  15. Antibiotic resistance - is resistance detected by surveillance relevant to predicting resistance in the clinical setting?

    PubMed

    Karlowsky, James A; Sahm, Daniel F

    2002-10-01

    Local, regional, national and global surveillance initiatives have several important functions, which include identifying shifts in antibiotic resistance, detecting the emergence of new resistance mechanisms and monitoring the impact of changes made to empiric prescribing, infection control and public health guidelines. Although the need for surveillance is indubitable and its use in the treatment of individual patients important, it cannot unequivocally predict outcomes in patients with infections. Treatment regimens for individual patients with suspected or demonstrated infections should be developed following consideration of symptoms, laboratory findings and relevant medical history, and in the context of appropriate local and widespread antibiotic resistance trends.

  16. Public Beliefs about Antibiotics, Infection and Resistance: A Qualitative Study

    PubMed Central

    Norris, Pauline; Chamberlain, Kerry; Dew, Kevin; Gabe, Jonathan; Hodgetts, Darrin; Madden, Helen

    2013-01-01

    We aimed to gain an in-depth understanding of public views and ways of talking about antibiotics. Four focus groups were held with members of the public. In addition, 39 households were recruited and interviews, diaries of medicine taking, diaries of any contact with medication were used to explore understanding and use of medication. Discussions related to antibiotics were identified and analyzed. Participants in this study were worried about adverse effects of antibiotics, particularly for recurrent infections. Some were concerned that antibiotics upset the body’s “balance”, and many used strategies to try to prevent and treat infections without antibiotics. They rarely used military metaphors about infection (e.g., describing bacteria as invading armies) but instead spoke of clearing infections. They had little understanding of the concept of antibiotic resistance but they thought that over-using antibiotics was unwise because it would reduce their future effectiveness. Previous studies tend to focus on problems such as lack of knowledge, or belief in the curative powers of antibiotics for viral illness, and neglect the concerns that people have about antibiotics, and the fact that many people try to avoid them. We suggest that these concerns about antibiotics form a resource for educating patients, for health promotion and social marketing strategies. PMID:27029314

  17. Multidrug Intrinsic Resistance Factors in Staphylococcus aureus Identified by Profiling Fitness within High-Diversity Transposon Libraries

    PubMed Central

    Rajagopal, Mithila; Martin, Melissa J.; Santiago, Marina; Lee, Wonsik; Kos, Veronica N.; Meredith, Tim

    2016-01-01

    ABSTRACT Staphylococcus aureus is a leading cause of life-threatening infections worldwide. The MIC of an antibiotic against S. aureus, as well as other microbes, is determined by the affinity of the antibiotic for its target in addition to a complex interplay of many other cellular factors. Identifying nontarget factors impacting resistance to multiple antibiotics could inform the design of new compounds and lead to more-effective antimicrobial strategies. We examined large collections of transposon insertion mutants in S. aureus using transposon sequencing (Tn-Seq) to detect transposon mutants with reduced fitness in the presence of six clinically important antibiotics—ciprofloxacin, daptomycin, gentamicin, linezolid, oxacillin, and vancomycin. This approach allowed us to assess the relative fitness of many mutants simultaneously within these libraries. We identified pathways/genes previously known to be involved in resistance to individual antibiotics, including graRS and vraFG (graRS/vraFG), mprF, and fmtA, validating the approach, and found several to be important across multiple classes of antibiotics. We also identified two new, previously uncharacterized genes, SAOUHSC_01025 and SAOUHSC_01050, encoding polytopic membrane proteins, as important in limiting the effectiveness of multiple antibiotics. Machine learning identified similarities in the fitness profiles of graXRS/vraFG, SAOUHSC_01025, and SAOUHSC_01050 mutants upon antibiotic treatment, connecting these genes of unknown function to modulation of crucial cell envelope properties. Therapeutic strategies that combine a known antibiotic with a compound that targets these or other intrinsic resistance factors may be of value for enhancing the activity of existing antibiotics for treating otherwise-resistant S. aureus strains. PMID:27531908

  18. Increases of Antibiotic Resistance in Excessive Use of Antibiotics in Smallholder Dairy Farms in Northern Thailand

    PubMed Central

    Suriyasathaporn, W.; Chupia, V.; Sing-Lah, T.; Wongsawan, K.; Mektrirat, R.; Chaisri, W.

    2012-01-01

    Antibiotic resistance patterns of bacterial isolates from both quarter teat-tip swabs and their quarter milk samples were evaluated in smallholder dairy farms in northern Thailand with excessive use of antibiotics (HIGH) compared with normal use (NORM). Results from teat-tip swab samples showed that the percentage of Bacillus spp. resistance to overall antibiotics was significantly lower in the NORM group than that of the HIGH group, whereas, the resistance percentage of coagulase-negative staphylococci in the NORM group was higher than that of the HIGH one. The overall mastitis-causing bacteria isolated from milk samples were environmental streptococci (13.8%), coagulase-negative staphylococci (9.9%), Staphylococcus aureus (5.4%), and Corynebacterium bovis (4.5%). Both staphylococci and streptococci had significantly higher percentages of resistance to cloxacillin and oxacillin in the HIGH group when compared to the NORM one. An occurrence of vancomycin-resistant bacteria was also observed in the HIGH group. In conclusion, the smallholder dairy farms with excessive use of antibiotics had a higher probability of antibiotic-resistant pattern than the farms with normal use. PMID:25049697

  19. Antibiotic and Antimicrobial Resistance: Threat Report 2013

    MedlinePlus

    ... resistant Staphylococcus aureus (MRSA) [page 77] Drug-resistant Streptococcus pneumoniae [page 79] Drug-resistant tuberculosis [page 81] Microorganisms with a Threat Level of Concerning Vancomycin-resistant Staphylococcus aureus ... Streptococcus [page 87] Clindamycin-resistant Group B Streptococcus [page ...

  20. Antibiotic resistance amongst healthcare-associated pathogens in China.

    PubMed

    Yezli, Saber; Li, Han

    2012-11-01

    The People's Republic of China, commonly known as China, comprises approximately one-fifth of the world's population. Because of the expanding size and density of its population and the frequent interaction of people with animals, China is a hotspot for the emergence and spread of new microbial threats and is a major contributor to the worldwide infectious disease burden. In recent years, the emergence and rapid spread of severe acute respiratory syndrome (SARS) generated considerable interest in the Chinese healthcare system and its infection control and prevention measures. This review examines antibiotic misuse and the status of antibiotic resistance in the Chinese healthcare system. China has high rates of antibiotic resistance driven by misuse of these agents in a healthcare system that provides strong incentives for overprescribing and in a country where self-medication is common. Tuberculosis remains a serious problem in China, with a high prevalence of multidrug-resistant and extensively drug-resistant strains. Drug resistance amongst nosocomial bacteria has been on a rapid upward trend with a strong inclination towards multidrug resistance. There is a need for effective infection prevention and control measures and strict use of antibiotics in China to control the rise and spread of antibiotic resistance in the country.

  1. Water Disinfection Byproducts Induce Antibiotic Resistance-Role of Environmental Pollutants in Resistance Phenomena.

    PubMed

    Li, Dan; Zeng, Siyu; He, Miao; Gu, April Z

    2016-03-15

    The spread of antibiotic resistance represents a global threat to public health, and has been traditionally attributed to extensive antibiotic uses in clinical and agricultural applications. As a result, researchers have mostly focused on clinically relevant high-level resistance enriched by antibiotics above the minimal inhibitory concentrations (MICs). Here, we report that two common water disinfection byproducts (chlorite and iodoacetic acid) had antibiotic-like effects that led to the evolution of resistant E. coli strains under both high (near MICs) and low (sub-MIC) exposure concentrations. The subinhibitory concentrations of DBPs selected strains with resistance higher than those evolved under above-MIC exposure concentrations. In addition, whole-genome analysis revealed distinct mutations in small sets of genes known to be involved in multiple drug and drug-specific resistance, as well as in genes not yet identified to play role in antibiotic resistance. The number and identities of genetic mutations were distinct for either the high versus low sub-MIC concentrations exposure scenarios. This study provides evidence and mechanistic insight into the sub-MIC selection of antibiotic resistance by antibiotic-like environmental pollutants such as disinfection byproducts in water, which may be important contributors to the spread of global antibiotic resistance. The results from this study open an intriguing and profound question on the roles of large amount and various environmental contaminants play in selecting and spreading the antibiotics resistance in the environment.

  2. ABC-F Proteins Mediate Antibiotic Resistance through Ribosomal Protection.

    PubMed

    Sharkey, Liam K R; Edwards, Thomas A; O'Neill, Alex J

    2016-03-22

    Members of the ABC-F subfamily of ATP-binding cassette proteins mediate resistance to a broad array of clinically important antibiotic classes that target the ribosome of Gram-positive pathogens. The mechanism by which these proteins act has been a subject of long-standing controversy, with two competing hypotheses each having gained considerable support: antibiotic efflux versus ribosomal protection. Here, we report on studies employing a combination of bacteriological and biochemical techniques to unravel the mechanism of resistance of these proteins, and provide several lines of evidence that together offer clear support to the ribosomal protection hypothesis. Of particular note, we show that addition of purified ABC-F proteins to anin vitrotranslation assay prompts dose-dependent rescue of translation, and demonstrate that such proteins are capable of displacing antibiotic from the ribosomein vitro To our knowledge, these experiments constitute the first direct evidence that ABC-F proteins mediate antibiotic resistance through ribosomal protection.IMPORTANCEAntimicrobial resistance ranks among the greatest threats currently facing human health. Elucidation of the mechanisms by which microorganisms resist the effect of antibiotics is central to understanding the biology of this phenomenon and has the potential to inform the development of new drugs capable of blocking or circumventing resistance. Members of the ABC-F family, which includelsa(A),msr(A),optr(A), andvga(A), collectively yield resistance to a broader range of clinically significant antibiotic classes than any other family of resistance determinants, although their mechanism of action has been controversial since their discovery 25 years ago. Here we present the first direct evidence that proteins of the ABC-F family act to protect the bacterial ribosome from antibiotic-mediated inhibition.

  3. Antibiotic resistance in primary and persistent endodontic infections

    PubMed Central

    Jungermann, Gretchen B.; Burns, Krystal; Nandakumar, Renu; Tolba, Mostafa; Venezia, Richard A.; Fouad, Ashraf F.

    2011-01-01

    Introduction The presence of antibiotic resistance genes in endodontic microorganisms may render the infection resistant to common antibiotics. The aims of this project were to identify selected antibiotics resistance genes in primary and persistent endodontic infections and determine the effectiveness of contemporary endodontic procedures in eliminating bacteria with these genes. Methods In patients undergoing primary endodontic treatment or retreatment, the root canals were aseptically accessed and sampled prior to endodontic procedures as well as following contemporary chemomechanical preparation and medication with calcium hydroxide. Identification of the following antibiotics resistance genes was performed using PCR: blaTEM−1, cfxA, blaZ, tetM, tetW, tetQ, vanA, vanD, and vanE. Limited phenotypic identification and antibiotic susceptibility verification was also performed. Results Overall, there were 45 specimens available for analysis: 30 from primary and 15 from persistent endodontic infections. In preoperative specimens, only blaTEM-1 was significantly more prevalent in primary vs. persistent infections (p=0.04). Following contemporary treatment procedures, there was an overall reduction in prevalence of these genes (p<0.001). blaTEM-1 and tetW were significantly reduced (p<0.05), cfxA, blaZ and tetQ were eliminated, but there was no change in tetM. No specimens contained vanA, vanD, or vanE. Antibiotic susceptibility testing showed significant differences among the antibiotics (p<0.001) and general concordance with the gene findings. Conclusions blaTEM-1 was more prevalent in primary than persistent infections. Vancomycin resistance was not present. The genes identified were reduced with treatment except for tetM. Genetic testing may be useful as a screening tool for antibiotic resistance. PMID:21924178

  4. The use of platensimycin and platencin to fight antibiotic resistance

    PubMed Central

    Allahverdiyev, Adil M; Bagirova, Melahat; Abamor, Emrah Sefik; Ates, Sezen Canim; Koc, Rabia Cakir; Miraloglu, Meral; Elcicek, Serhat; Yaman, Serkan; Unal, Gokce

    2013-01-01

    Infectious diseases are known as one of the most life-threatening disabilities worldwide. Approximately 13 million deaths related to infectious diseases are reported each year. The only way to combat infectious diseases is by chemotherapy using antimicrobial agents and antibiotics. However, due to uncontrolled and unnecessary use of antibiotics in particular, surviving bacteria have evolved resistance against several antibiotics. Emergence of multidrug resistance in bacteria over the past several decades has resulted in one of the most important clinical health problems in modern medicine. For instance, approximately 440,000 new cases of multidrug-resistant tuberculosis are reported every year leading to the deaths of 150,000 people worldwide. Management of multidrug resistance requires understanding its molecular basis and the evolution and dissemination of resistance; development of new antibiotic compounds in place of traditional antibiotics; and innovative strategies for extending the life of antibiotic molecules. Researchers have begun to develop new antimicrobials for overcoming this important problem. Recently, platensimycin – isolated from extracts of Streptomyces platensis – and its analog platencin have been defined as promising agents for fighting multidrug resistance. In vitro and in vivo studies have shown that these new antimicrobials have great potential to inhibit methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae by targeting type II fatty acid synthesis in bacteria. Showing strong efficacy without any observed in vivo toxicity increases the significance of these antimicrobial agents for their use in humans. However, at the present time, clinical trials are insufficient and require more research. The strong antibacterial efficacies of platensimycin and platencin may be established in clinical trials and their use in humans for coping with multidrug resistance may be

  5. Prevalence of antibiotic resistance genes in antibiotic-resistant Escherichia coli isolates in surface water of Taihu Lake Basin, China.

    PubMed

    Zhang, Song He; Lv, Xiaoyang; Han, Bing; Gu, Xiucong; Wang, Pei Fang; Wang, Chao; He, Zhenli

    2015-08-01

    The rapid development of antibiotic-resistant bacteria (ARB) has been of concern worldwide. In this study, antibiotic resistance genes (ARGs) were investigated in antibiotic-resistant Escherichia coli isolated from surface water samples (rivers, n = 17; Taihu Lake, n = 16) and from human, chicken, swine, and Egretta garzetta sources in the Taihu Basin. E. coli showing resistance to at least five drugs occurred in 31, 67, 58, 27, and 18% of the isolates from surface water (n = 665), chicken (n = 27), swine (n = 29), human (n = 45), and E. garzetta (n = 15) sources, respectively. The mean multi-antibiotic resistance (MAR) index of surface water samples (0.44) was lower than that of chicken (0.64) and swine (0.57) sources but higher than that of human (0.30) and E. garzetta sources (0.15). Ten tetracycline, four sulfonamide, four quinolone, five β-lactamase, and two streptomycin resistance genes were detected in the corresponding antibiotic-resistant isolates. Most antibiotic-resistant E. coli harbored at least two similar functional ARGs. Int-I was detected in at least 57% of MAR E. coli isolates. The results of multiple correspondence analysis and Spearman correlation analysis suggest that antibiotic-resistant E. coli in water samples were mainly originated from swine, chicken, and/or human sources. Most of the ARGs detected in E. garzetta sources were prevalent in other sources. These data indicated that human activities may have contributed to the spread of ARB in the aquatic environment.

  6. Surveillance and Control of Antibiotic Resistance in the Mediterranean Region

    PubMed Central

    Ricciardi, Walter; Giubbini, Gabriele; Laurenti, Patrizia

    2016-01-01

    Antibiotic resistance is one of the most relevant problems in the healthcare: the growth of resistant microorganisms in healthcare settings is a worrisome threat, raising length to stay (LOS), morbidity and mortality in those patients. The importance of the antibiotic resistance and its spread around the world, gave rise to the activation of several surveillance systems, based especially on the collection of laboratory data to local or national level. The objective of this work is to carry out a review of the scientific literature existing on the topic and scientific activities related to surveillance of antibiotic resistance in the countries bordering the Mediterranean Sea. Recent Data from European Centre for Disease Prevention and Control (November 2015) show, for different combinations bacterium-drug, an increase of resistance from North to South and from West to East of Europe. It is of particular concern the phenomenon of resistance carried out by some gram-negative, specifically Klebsiella pneumoniae and Escherichia coli to third-generation cephalosporin, often combined in opposition to fluoroquinolones and aminoglycosides. Is particularly high the incidence of resistance to carbapenems by strains of Enterobacteriaceae (Klebsiella included). The resistance exerted by MRSA (Methicillin-resistant Staphylococcus aureus) continues to be relevant, albeit showing some decline in recent years. The incidence of resistance carried on by Streptococcus pneumoniae is stable and is mainly relevant to macrolides. Finally, a significant increase in recording relatively exercised by Enterococcus faecium to Vancomycin. Detecting, preventing, and controlling antibiotic resistance requires strategic, coordinated, and sustained efforts. It also depends on the engagement of governments, academia, industry, healthcare providers, the general public, and the agricultural community, as well as international partners. Committing to combating antibiotic-resistant microbes does support

  7. Ready for a world without antibiotics? The Pensières Antibiotic Resistance Call to Action

    PubMed Central

    2012-01-01

    Resistance to antibiotics has increased dramatically over the past few years and has now reached a level that places future patients in real danger. Microorganisms such as Escherichia coli and Klebsiella pneumoniae, which are commensals and pathogens for humans and animals, have become increasingly resistant to third-generation cephalosporins. Moreover, in certain countries, they are also resistant to carbapenems and therefore susceptible only to tigecycline and colistin. Resistance is primarily attributed to the production of beta-lactamase genes located on mobile genetic elements, which facilitate their transfer between different species. In some rare cases, Gram-negative rods are resistant to virtually all known antibiotics. The causes are numerous, but the role of the overuse of antibiotics in both humans and animals is essential, as well as the transmission of these bacteria in both the hospital and the community, notably via the food chain, contaminated hands, and between animals and humans. In addition, there are very few new antibiotics in the pipeline, particularly for Gram-negative bacilli. The situation is slightly better for Gram-positive cocci as some potent and novel antibiotics have been made available in recent years. A strong and coordinated international programme is urgently needed. To meet this challenge, 70 internationally recognized experts met for a two-day meeting in June 2011 in Annecy (France) and endorsed a global call to action ("The Pensières Antibiotic Resistance Call to Action"). Bundles of measures that must be implemented simultaneously and worldwide are presented in this document. In particular, antibiotics, which represent a treasure for humanity, must be protected and considered as a special class of drugs. PMID:22958833

  8. Mobile antibiotic resistance - the spread of genes determining the resistance of bacteria through food products.

    PubMed

    Godziszewska, Jolanta; Guzek, Dominika; Głąbski, Krzysztof; Wierzbicka, Agnieszka

    2016-07-07

    In recent years, more and more antibiotics have become ineffective in the treatment of bacterial nfections. The acquisition of antibiotic resistance by bacteria is associated with circulation of genes in the environment. Determinants of antibiotic resistance may be transferred to pathogenic bacteria. It has been shown that conjugation is one of the key mechanisms responsible for spread of antibiotic resistance genes, which is highly efficient and allows the barrier to restrictions and modifications to be avoided. Some conjugative modules enable the transfer of plasmids even between phylogenetically distant bacterial species. Many scientific reports indicate that food is one of the main reservoirs of these genes. Antibiotic resistance genes have been identified in meat products, milk, fruits and vegetables. The reason for such a wide spread of antibiotic resistance genes is the overuse of antibiotics by breeders of plants and animals, as well as by horizontal gene transfer. It was shown, that resistance determinants located on mobile genetic elements, which are isolated from food products, can easily be transferred to another niche. The antibiotic resistance genes have been in the environment for 30 000 years. Their removal from food products is not possible, but the risks associated with the emergence of multiresistant pathogenic strains are very large. The only option is to control the emergence, selection and spread of these genes. Therefore measures are sought to prevent horizontal transfer of genes. Promising concepts involve the combination of developmental biology, evolution and ecology in the fight against the spread of antibiotic resistance.

  9. Potential impact of environmental bacteriophages in spreading antibiotic resistance genes.

    PubMed

    Muniesa, Maite; Colomer-Lluch, Marta; Jofre, Juan

    2013-06-01

    The idea that bacteriophage transduction plays a role in the horizontal transfer of antibiotic resistance genes is gaining momentum. Such transduction might be vital in horizontal transfer from environmental to human body-associated biomes and here we review many lines of evidence supporting this notion. It is well accepted that bacteriophages are the most abundant entities in most environments, where they have been shown to be quite persistent. This fact, together with the ability of many phages to infect bacteria belonging to different taxa, makes them suitable vehicles for gene transfer. Metagenomic studies confirm that substantial percentages of the bacteriophage particles present in most environments contain bacterial genes, including mobile genetic elements and antibiotic resistance genes. When specific genes of resistance to antibiotics are detected by real-time PCR in the bacteriophage populations of different environments, only tenfold lower numbers of these genes are observed, compared with those found in the corresponding bacterial populations. In addition, the antibiotic resistance genes from these bacteriophages are functional and generate resistance to the bacteria when these genes are transfected. Finally, reports about the transduction of antibiotic resistance genes are on the increase.

  10. Plant derived compounds inactivate antibiotic resistant Campylobacter jejuni strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sixty-three Campylobacter isolates were screened for their resistance to the antibiotics ampicillin, cefaclor, ciprofloxacin, erythromycin, gentamycin, tetracycline, and trimethroprim/sulfamethoxazole. Based on this screen, the resistant strains D28a and H2a and the nonresistant strain A24a were se...

  11. Nationwide survey of Helicobacter pylori antibiotic resistance in Thailand.

    PubMed

    Vilaichone, Ratha-Korn; Gumnarai, Pornpen; Ratanachu-Ek, Thawee; Mahachai, Varocha

    2013-12-01

    The objectives of this study are to survey the antibiotic-resistant pattern of Helicobacter pylori infection in different geographical locations in Thailand and to determine factors associated with antibiotic resistance. Dyspeptic patients undergoing upper gastrointestinal endoscopy from the Northern, Northeastern, Central, and Southern regions of Thailand between January 2004 and December 2012 were enrolled in this study. Two antral gastric biopsies were obtained for culture; susceptibility tests were performed using E-test. A total of 3964 were enrolled, and 1350 patients (34.1%) were infected with H. pylori as identified by rapid urease test. Cultures were positive in 619 isolates. E-test for amoxicillin, clarithromycin, metronidazole, and tetracycline were successful in 400 isolates and for levofloxacin and ciprofloxacin in 208 isolates. Antibiotic resistance was present in 50.3% including amoxicillin 5.2%, tetracycline 1.7%, clarithromycin 3.7%, metronidazole 36%, ciprofloxacin 7.7%, levofloxacin 7.2%, and multi-drugs in 4.2%. Clarithromycin resistance was significantly more common in those older than 40 years (i.e., 100% versus 0%; P = 0.04). The prevalence of metronidazole resistant in Southern Thailand was significantly higher than in the Northeastern region (66.7% versus 33.3% P = 0.04). Metronidazole resistance remains the most common antibiotic resistant type of H. pylori in Thailand. The pattern of H. pylori antibiotic resistance over 9 years demonstrated a fall in clarithromycin resistance such that currently age >40 years is a predictor for clarithromycin resistance in Thailand. Quinolone resistance is a growing problem.

  12. Antibiotic concentration and antibiotic-resistant bacteria in two shallow urban lakes after stormwater event.

    PubMed

    Zhang, Songhe; Pang, Si; Wang, PeiFang; Wang, Chao; Han, Nini; Liu, Bin; Han, Bing; Li, Yi; Anim-Larbi, Kwaku

    2016-05-01

    Stormwater runoff is generally characterized as non-point source pollution. In the present study, antibiotic concentration and antibiotic susceptibilities of cultivable heterotrophic bacteria were investigated in two small shallow urban lakes before and after strong storm event. Several antibiotics, lactose-fermenting bacteria and cultivable heterotrophic bacteria concentrations increased in surface water and/or surface sediment of two small urban lakes (Lake Xuanwu and Wulongtan) after strong storm event. In general, the frequencies of bacteria showing resistance to nine antibiotics increased after storm event. Based on the 16S rRNA genes of 50 randomly selected isolates from each water sample of two lakes, Aeromonas and Bacillus were dominant genera in samples from two lakes, while genera Proteus and Lysinibacillus were the third abundant genera in Lake Xuanwu and Wulongtu, respectively. Presences of nine antibiotic resistance genes (ARGs) in the 100 isolates were detected and most of these isolates harbored at least two ARGs with different functions. The detection frequency of ARGs in Gram-negative isolates was higher than that in Gram-positive isolates. The most prevalent integron in 100 isolates was int(II) (n = 28), followed by int(I) (n = 17) and int(III) (n = 17). Our results indicate that strong storm events potentially contribute to the transfer of ARGs and antibiotic-resistant bacteria from land-sewer system to the urban Lakes.

  13. Childhood infections, antibiotics, and resistance: what are parents saying now?

    PubMed Central

    Finkelstein, Jonathan A.; Dutta-Linn, Maya; Meyer, Robert; Goldman, Roberta

    2014-01-01

    Parental misconceptions and even “demand” for unnecessary antibiotics were previously viewed as contributors to overuse of these agents. We conducted focus groups to explore the knowledge and attitudes surrounding common infections and antibiotic use in the current era of more judicious prescribing. Among diverse groups of parents, we found widespread use of home remedies and considerable concern regarding antibiotic resistance. Parents generally expressed the desire to use antibiotics only when necessary. There was appreciation of inherent error in the diagnosis of common infections, with most trust placed in providers with whom parents had longstanding relationships. While some parents had experience with “watchful waiting” for otitis media, there was little enthusiasm for this approach. While there may still be room for further education, it appears that parents have become more informed and sophisticated regarding appropriate uses of antibiotics. This has likely contributed to the declines seen in their use nationally. PMID:24137024

  14. Diversity and antibiotic resistance in Pseudomonas spp. from drinking water.

    PubMed

    Vaz-Moreira, Ivone; Nunes, Olga C; Manaia, Célia M

    2012-06-01

    Pseudomonas spp. are common inhabitants of aquatic environments, including drinking water. Multi-antibiotic resistance in clinical isolates of P. aeruginosa is widely reported and deeply characterized. However, the information regarding other species and environmental isolates of this genus is scant. This study was designed based on the hypothesis that members of the genus Pseudomonas given their high prevalence, wide distribution in waters and genetic plasticity can be important reservoirs of antibiotic resistance in drinking water. With this aim, the diversity and antibiotic resistance phenotypes of Pseudomonas isolated from different drinking water sources were evaluated. The genotypic diversity analyses were based on six housekeeping genes (16S rRNA, rpoD, rpoB, gyrB, recA and ITS) and on pulsed field gel electrophoresis. Susceptibility to 21 antibiotics of eight classes was tested using the ATB PSE EU (08) and disk diffusion methods. Pseudomonas spp. were isolated from 14 of the 32 sampled sites. A total of 55 non-repetitive isolates were affiliated to twenty species. Although the same species were isolated from different sampling sites, identical genotypes were never observed in distinct types of water (water treatment plant/distribution system, tap water, cup fillers, biofilm, and mineral water). In general, the prevalence of antibiotic resistance was low and often the resistance patterns were related with the species and/or the strain genotype. Resistance to ticarcillin, ticarcillin with clavulanic acid, fosfomycin and cotrimoxazol were the most prevalent (69-84%). No resistance to piperacillin, levofloxacin, ciprofloxacin, tetracycline, gentamicin, tobramycin, amikacin, imipenem or meropenem was observed. This study demonstrates that Pseudomonas spp. are not so widespread in drinking water as commonly assumed. Nevertheless, it suggests that water Pseudomonas can spread acquired antibiotic resistance, preferentially via vertical transmission.

  15. Simultaneous breakdown of multiple antibiotic resistance mechanisms in S. aureus.

    PubMed

    Kaneti, Galoz; Sarig, Hadar; Marjieh, Ibrahim; Fadia, Zaknoon; Mor, Amram

    2013-12-01

    In previous studies, the oligo-acyl-lysyl (OAK) C12(ω7)K-β12 added to cultures of gram-positive bacteria exerted a bacteriostatic activity that was associated with membrane depolarization, even at high concentrations. Here, we report that multidrug-resistant Staphylococcus aureus strains, unlike other gram-positive species, have reverted to the sensitive phenotype when exposed to subminimal inhibitory concentrations (sub-MICs) of the OAK, thereby increasing antibiotics potency by up to 3 orders of magnitude. Such chemosensitization was achieved using either cytoplasm or cell-wall targeting antibiotics. Moreover, eventual emergence of resistance to antibiotics was significantly delayed. Using the mouse peritonitis-sepsis model, we show that on single-dose administration of oxacillin and OAK combinations, death induced by a lethal staphylococcal infection was prevented in a synergistic manner, thereby supporting the likelihood for synergism to persist under in vivo conditions. Toward illuminating the molecular basis for these observations, we present data arguing that sub-MIC OAK interactions with the plasma membrane can inhibit proton-dependent signal transduction responsible for expression and export of resistance factors, as demonstrated for β-lactamase and PBP2a. Collectively, the data reveal a potentially useful approach for overcoming antibiotic resistance and for preventing resistance from emerging as readily as when bacteria are exposed to an antibiotic alone.

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

    PubMed Central

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

    2017-01-01

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

  17. Sponge Microbiota Are a Reservoir of Functional Antibiotic Resistance Genes

    PubMed Central

    Versluis, Dennis; Rodriguez de Evgrafov, Mari; Sommer, Morten O. A.; Sipkema, Detmer; Smidt, Hauke; van Passel, Mark W. J.

    2016-01-01

    Wide application of antibiotics has contributed to the evolution of multi-drug resistant human pathogens, resulting in poorer treatment outcomes for infections. In the marine environment, seawater samples have been investigated as a resistance reservoir; however, no studies have methodically examined sponges as a reservoir of antibiotic resistance. Sponges could be important in this respect because they often contain diverse microbial communities that have the capacity to produce bioactive metabolites. Here, we applied functional metagenomics to study the presence and diversity of functional resistance genes in the sponges Aplysina aerophoba, Petrosia ficiformis, and Corticium candelabrum. We obtained 37 insert sequences facilitating resistance to D-cycloserine (n = 6), gentamicin (n = 1), amikacin (n = 7), trimethoprim (n = 17), chloramphenicol (n = 1), rifampicin (n = 2) and ampicillin (n = 3). Fifteen of 37 inserts harbored resistance genes that shared <90% amino acid identity with known gene products, whereas on 13 inserts no resistance gene could be identified with high confidence, in which case we predicted resistance to be mainly mediated by antibiotic efflux. One marine-specific ampicillin-resistance-conferring β-lactamase was identified in the genus Pseudovibrio with 41% global amino acid identity to the closest β-lactamase with demonstrated functionality, and subsequently classified into a new family termed PSV. Taken together, our results show that sponge microbiota host diverse and novel resistance genes that may be harnessed by phylogenetically distinct bacteria. PMID:27909433

  18. Clinical, economic and societal impact of antibiotic resistance.

    PubMed

    Barriere, Steven L

    2015-02-01

    The concern over antibiotic resistance has been voiced since the discovery of modern antibiotics > 75 years ago. The concerns have only increased with time, with efforts to control resistance caused by widespread overuse of antibiotics in human medicine and far more than appreciated use in the feeding of animals for human consumption to promote growth. The problem is worldwide, but certain regions and selected health care institutions report far more resistance, including strains of Gram-negative bacteria that are susceptible only to the once discarded drugs polymyxin B or colistin, and pan-resistant strains are on the rise. One of the central efforts to control resistance, apart from antimicrobial stewardship, is the development of new antimicrobial agents. This has lagged significantly over the past 10 - 15 years, for a variety of reasons; but promising new agents are being developed, unfortunately none thus far addressing all potentially resistant strains. There is the unlikely, but not unreal, possibility that we could return to a pre-antibiotic era, where morbidity and mortality rates have risen dramatically and routine surgical procedures are not performed for fear of post-operative infections. The onus of control of resistance is a moral imperative that falls on the shoulders of all.

  19. Oral antibiotics are effective for highly resistant hip arthroplasty infections.

    PubMed

    Cordero-Ampuero, José; Esteban, Jaime; García-Cimbrelo, Eduardo

    2009-09-01

    Infected arthroplasties reportedly have a lower eradication rate when caused by highly resistant and/or polymicrobial isolates and in these patients most authors recommend intravenous antibiotics. We asked whether two-stage revision with interim oral antibiotics could eradicate these infections. We prospectively followed 36 patients (mean age, 71.8 years) with late hip arthroplasty infections. Combinations of oral antibiotics were prescribed according to cultures, biofilm, and intracellular effectiveness. The minimum followup was 1 year (mean, 4.4 years; range, 1-12 years). We presumed eradication in the absence of clinical, serologic, and radiographic signs of infection. Infection was eradicated in all 13 patients with highly resistant bacteria who completed a two-stage protocol (10 with methicillin-resistant Staphylococci) and in eight of 11 patients treated with only the first stage (and six of nine with methicillin-resistant Staphylococci). Infection was eradicated in six of six patients with polymicrobial isolates (of sensitive and/or resistant bacteria) who completed a two-stage protocol and in five of seven with polymicrobial isolates treated with only the first surgery. The Harris hip score averaged 88.1 (range, 70-98) in patients who underwent reimplantation and 56.8 (range, 32-76) in patients who underwent resection arthroplasty. Long cycles of combined oral antibiotics plus a two-stage surgical exchange appear a promising alternative for infections by highly resistant bacteria, methicillin-resistant Staphylococci, and polymicrobial infections.

  20. Diverse and abundant antibiotic resistance genes in Chinese swine farms.

    PubMed

    Zhu, Yong-Guan; Johnson, Timothy A; Su, Jian-Qiang; Qiao, Min; Guo, Guang-Xia; Stedtfeld, Robert D; Hashsham, Syed A; Tiedje, James M

    2013-02-26

    Antibiotic resistance genes (ARGs) are emerging contaminants posing a potential worldwide human health risk. Intensive animal husbandry is believed to be a major contributor to the increased environmental burden of ARGs. Despite the volume of antibiotics used in China, little information is available regarding the corresponding ARGs associated with animal farms. We assessed type and concentrations of ARGs at three stages of manure processing to land disposal at three large-scale (10,000 animals per year) commercial swine farms in China. In-feed or therapeutic antibiotics used on these farms include all major classes of antibiotics except vancomycins. High-capacity quantitative PCR arrays detected 149 unique resistance genes among all of the farm samples, the top 63 ARGs being enriched 192-fold (median) up to 28,000-fold (maximum) compared with their respective antibiotic-free manure or soil controls. Antibiotics and heavy metals used as feed supplements were elevated in the manures, suggesting the potential for coselection of resistance traits. The potential for horizontal transfer of ARGs because of transposon-specific ARGs is implicated by the enrichment of transposases--the top six alleles being enriched 189-fold (median) up to 90,000-fold in manure--as well as the high correlation (r(2) = 0.96) between ARG and transposase abundance. In addition, abundance of ARGs correlated directly with antibiotic and metal concentrations, indicating their importance in selection of resistance genes. Diverse, abundant, and potentially mobile ARGs in farm samples suggest that unmonitored use of antibiotics and metals is causing the emergence and release of ARGs to the environment.

  1. Antibiotics in animal feed and their role in resistance development.

    PubMed

    Wegener, Henrik C

    2003-10-01

    Animals and humans constitute overlapping reservoirs of resistance, and consequently use of antimicrobials in animals can impact on public health. For example, the occurrence of vancomycin-resistant enterococci in food-animals is associated with the use of avoparcin, a glycopeptide antibiotic used as a feed additive for the growth promotion of animals. Vancomycin-resistant enterococci and vancomycin resistance determinants can therefore spread from animals to humans. The bans on avoparcin and other antibiotics as growth promoters in the EU have provided scientists with a unique opportunity to investigate the effects of the withdrawal of a major antimicrobial selective pressure on the occurrence and spread of antimicrobial resistance. The data shows that although the levels of resistance in animals and food, and consequently in humans, has been markedly reduced after the termination of use, the effects on animal health and productivity have been very minor.

  2. [Epidemiological overview of antibiotic resistance in France and worldwide].

    PubMed

    Arlet, Guillaume

    2012-09-01

    Antibiotic resistance appeared early after the introduction of these molecules in therapeutic. But, this resistance has long been confined to care facilities. Twenty years ago, resistance emerged in community with the methicillin resistance in Staphylococcus aureus and also with the reduced susceptibility to penicillin in pneumococci, which are good examples. Fortunately, for these two species, in France, the situation appears to be controlled. The most worrying now is the emergence of resistance to major antimicrobial agents in Escherichia coli both in community and in hospitals. The third-generation cephalosporins and the fluoroquinolones are concerned. This situation is currently not well controlled here and worldwide. The only recourse remaining carbapenems, antibiotics reserved for hospital use. Unfortunately, new mechanisms of resistance to these molecules are emerging.

  3. Anthropogenic antibiotic resistance genes mobilization to the polar regions.

    PubMed

    Hernández, Jorge; González-Acuña, Daniel

    2016-01-01

    Anthropogenic influences in the southern polar region have been rare, but lately microorganisms associated with humans have reached Antarctica, possibly from military bases, fishing boats, scientific expeditions, and/or ship-borne tourism. Studies of seawater in areas of human intervention and proximal to fresh penguin feces revealed the presence of Escherichia coli strains least resistant to antibiotics in penguins, whereas E. coli from seawater elsewhere showed resistance to one or more of the following antibiotics: ampicillin, tetracycline, streptomycin, and trim-sulfa. In seawater samples, bacteria were found carrying extended-spectrum β-lactamase (ESBL)-type CTX-M genes in which multilocus sequencing typing (MLST) showed different sequence types (STs), previously reported in humans. In the Arctic, on the contrary, people have been present for a long time, and the presence of antibiotic resistance genes (ARGs) appears to be much more wide-spread than was previously reported. Studies of E coli from Arctic birds (Bering Strait) revealed reduced susceptibility to antibiotics, but one globally spreading clone of E. coli genotype O25b-ST131, carrying genes of ESBL-type CTX-M, was identified. In the few years between sample collections in the same area, differences in resistance pattern were observed, with E. coli from birds showing resistance to a maximum of five different antibiotics. Presence of resistance-type ESBLs (TEM, SHV, and CTX-M) in E. coli and Klebsiella pneumoniae was also confirmed by specified PCR methods. MLST revealed that those bacteria carried STs that connect them to previously described strains in humans. In conclusion, bacteria previously related to humans could be found in relatively pristine environments, and presently human-associated, antibiotic-resistant bacteria have reached a high global level of distribution that they are now found even in the polar regions.

  4. Anthropogenic antibiotic resistance genes mobilization to the polar regions

    PubMed Central

    Hernández, Jorge; González-Acuña, Daniel

    2016-01-01

    Anthropogenic influences in the southern polar region have been rare, but lately microorganisms associated with humans have reached Antarctica, possibly from military bases, fishing boats, scientific expeditions, and/or ship-borne tourism. Studies of seawater in areas of human intervention and proximal to fresh penguin feces revealed the presence of Escherichia coli strains least resistant to antibiotics in penguins, whereas E. coli from seawater elsewhere showed resistance to one or more of the following antibiotics: ampicillin, tetracycline, streptomycin, and trim-sulfa. In seawater samples, bacteria were found carrying extended-spectrum β-lactamase (ESBL)-type CTX-M genes in which multilocus sequencing typing (MLST) showed different sequence types (STs), previously reported in humans. In the Arctic, on the contrary, people have been present for a long time, and the presence of antibiotic resistance genes (ARGs) appears to be much more wide-spread than was previously reported. Studies of E coli from Arctic birds (Bering Strait) revealed reduced susceptibility to antibiotics, but one globally spreading clone of E. coli genotype O25b-ST131, carrying genes of ESBL-type CTX-M, was identified. In the few years between sample collections in the same area, differences in resistance pattern were observed, with E. coli from birds showing resistance to a maximum of five different antibiotics. Presence of resistance-type ESBLs (TEM, SHV, and CTX-M) in E. coli and Klebsiella pneumoniae was also confirmed by specified PCR methods. MLST revealed that those bacteria carried STs that connect them to previously described strains in humans. In conclusion, bacteria previously related to humans could be found in relatively pristine environments, and presently human-associated, antibiotic-resistant bacteria have reached a high global level of distribution that they are now found even in the polar regions. PMID:27938628

  5. Pervasive selection for and against antibiotic resistance in inhomogeneous multistress environments.

    PubMed

    Chait, Remy; Palmer, Adam C; Yelin, Idan; Kishony, Roy

    2016-01-20

    Antibiotic-sensitive and -resistant bacteria coexist in natural environments with low, if detectable, antibiotic concentrations. Except possibly around localized antibiotic sources, where resistance can provide a strong advantage, bacterial fitness is dominated by stresses unaffected by resistance to the antibiotic. How do such mixed and heterogeneous conditions influence the selective advantage or disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels of tetracyclines potentiate selection for or against tetracycline resistance around localized sources of almost any toxin or stress. Furthermore, certain stresses generate alternating rings of selection for and against resistance around a localized source of the antibiotic. In these conditions, localized antibiotic sources, even at high strengths, can actually produce a net selection against resistance to the antibiotic. Our results show that interactions between the effects of an antibiotic and other stresses in inhomogeneous environments can generate pervasive, complex patterns of selection both for and against antibiotic resistance.

  6. Rapid determination of antibiotic resistance in E. coli using dielectrophoresis

    NASA Astrophysics Data System (ADS)

    Hoettges, Kai F.; Dale, Jeremy W.; Hughes, Michael P.

    2007-09-01

    In recent years, infections due to antibiotic-resistant strains of bacteria such as methillicin-resistant Staphylococcus aureus and ciprofloxacin-resistant Escherichia coli are on the rise, and with them the demand for rapid antibiotic testing is also rising. Conventional tests, such as disc diffusion testing, require a primary sample to be tested in the presence of a number of antibiotics to verify which antibiotics suppress growth, which take approximately 24 h to complete and potentially place the patient at severe risk. In this paper we describe the use of dielectrophoresis as a rapid marker of cell death, by detecting changes in the electrophysiology of the cell caused by the administration of an antibiotic. In contrast to other markers, the electrophysiology of the cell changes rapidly during cell death allowing live cells to be distinguished from dead (or dying) cells without the need for culturing. Using polymyxin B as an example antibiotic, our studies indicate that significant changes in cell characteristics can be observed as soon as 1 h passes after isolating a culture from nutrient broth.

  7. A new antibiotic kills pathogens without detectable resistance.

    PubMed

    Ling, Losee L; Schneider, Tanja; Peoples, Aaron J; Spoering, Amy L; Engels, Ina; Conlon, Brian P; Mueller, Anna; Schäberle, Till F; Hughes, Dallas E; Epstein, Slava; Jones, Michael; Lazarides, Linos; Steadman, Victoria A; Cohen, Douglas R; Felix, Cintia R; Fetterman, K Ashley; Millett, William P; Nitti, Anthony G; Zullo, Ashley M; Chen, Chao; Lewis, Kim

    2015-01-22

    Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99% of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid II (precursor of peptidoglycan) and lipid III (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.

  8. Antibiotic administration routes significantly influence the levels of antibiotic resistance in gut microbiota.

    PubMed

    Zhang, Lu; Huang, Ying; Zhou, Yang; Buckley, Timothy; Wang, Hua H

    2013-08-01

    This study examined the impact of oral exposure to antibiotic-resistant bacteria and antibiotic administration methods on antibiotic resistance (AR) gene pools and the profile of resistant bacteria in host gastrointestinal (GI) tracts using C57BL/6J mice with natural gut microbiota. Mice inoculated with a mixture of tet(M)-carrying Enterococcus spp. or blaCMY-2-carrying Escherichia coli were treated with different doses of tetracycline hydrochloride (Tet) or ampicillin sodium (Amp) and delivered via either feed or intravenous (i.v.) injection. Quantitative PCR assessment of mouse fecal samples revealed that (i) AR gene pools were below the detection limit in mice without prior inoculation of AR gene carriers regardless of subsequent exposure to corresponding antibiotics; (ii) oral exposure to high doses of Tet and Amp in mice inoculated with AR gene carriers led to rapid enrichment of corresponding AR gene pools in feces; (iii) significantly less or delayed development of AR in the GI tract of the AR carrier-inoculated mice was observed when the same doses of antibiotics were administered via i.v. injection rather than oral administration; and (iv) antibiotic dosage, and maybe the excretion route, affected AR in the GI tract. The shift of dominant AR bacterial populations in the gut microbiota was consistent with the dynamics of AR gene pools. The emergence of endogenous resistant bacteria in the gut microbiota corresponding to drug exposure was also observed. Together, these data suggest that oral administration of antibiotics has a prominent effect on AR amplification and development in gut microbiota, which may be minimized by alternative drug administration approaches, as illustrated by i.v. injection in this study and proper drug selection.

  9. Genomic and metagenomic technologies to explore the antibiotic resistance mobilome.

    PubMed

    Martínez, José L; Coque, Teresa M; Lanza, Val F; de la Cruz, Fernando; Baquero, Fernando

    2017-01-01

    Antibiotic resistance is a relevant problem for human health that requires global approaches to establish a deep understanding of the processes of acquisition, stabilization, and spread of resistance among human bacterial pathogens. Since natural (nonclinical) ecosystems are reservoirs of resistance genes, a health-integrated study of the epidemiology of antibiotic resistance requires the exploration of such ecosystems with the aim of determining the role they may play in the selection, evolution, and spread of antibiotic resistance genes, involving the so-called resistance mobilome. High-throughput sequencing techniques allow an unprecedented opportunity to describe the genetic composition of a given microbiome without the need to subculture the organisms present inside. However, bioinformatic methods for analyzing this bulk of data, mainly with respect to binning each resistance gene with the organism hosting it, are still in their infancy. Here, we discuss how current genomic methodologies can serve to analyze the resistance mobilome and its linkage with different bacterial genomes and metagenomes. In addition, we describe the drawbacks of current methodologies for analyzing the resistance mobilome, mainly in cases of complex microbiotas, and discuss the possibility of implementing novel tools to improve our current metagenomic toolbox.

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

    PubMed

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

    2016-04-01

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

  11. Urinary tract infections: bacteriology and antibiotic resistance patterns.

    PubMed

    Mashouf, Rasoul Yousefi; Babalhavaeji, Hooshang; Yousef, Javad

    2009-07-01

    The aim of this study was to identify the bacteria causing community acquired urinary tract infections (UTI) and detection of antibiotics resistance of isolates in 912 children below 18 years in the west of Iran. Data were analyzed for 4 age groups: infants, toddlers, preteens and teens. Fourteen antibiotics were tested by gel-diffusion method. Of 912 patients, 34.2% had positive bacterial cultures. The most common isolates were E. coli (57.4 %), K. pneumoniae (9.7 %), S. aureus (5.8%) and A. baumannii (2.2%). Most isolates showed high resistance against ampicillin, cotrimoxazole, nalidixic acid, tobramycin and nitrofurantoin. Klebsiella isolates showed more resistance against tested antibiotics than E. coli isolates.

  12. Label-free SRM-based relative quantification of antibiotic resistance mechanisms in Pseudomonas aeruginosa clinical isolates.

    PubMed

    Charretier, Yannick; Köhler, Thilo; Cecchini, Tiphaine; Bardet, Chloé; Cherkaoui, Abdessalam; Llanes, Catherine; Bogaerts, Pierre; Chatellier, Sonia; Charrier, Jean-Philippe; Schrenzel, Jacques

    2015-01-01

    Both acquired and intrinsic mechanisms play a crucial role in Pseudomonas aeruginosa antibiotic resistance. Many clinically relevant resistance mechanisms result from changes in gene expression, namely multidrug efflux pump overproduction, AmpC β-lactamase induction or derepression, and inactivation or repression of the carbapenem-specific porin OprD. Changes in gene expression are usually assessed using reverse-transcription quantitative real-time PCR (RT-qPCR) assays. Here, we evaluated label-free Selected Reaction Monitoring (SRM)-based mass spectrometry to directly quantify proteins involved in antibiotic resistance. We evaluated the label-free SRM using a defined set of P. aeruginosa isolates with known resistance mechanisms and compared it with RT-qPCR. Referring to efflux systems, we found a more robust relative quantification of antibiotic resistance mechanisms by SRM than RT-qPCR. The SRM-based approach was applied to a set of clinical P. aeruginosa isolates to detect antibiotic resistance proteins. This multiplexed SRM-based approach is a rapid and reliable method for the simultaneous detection and quantification of resistance mechanisms and we demonstrate its relevance for antibiotic resistance prediction.

  13. Label-free SRM-based relative quantification of antibiotic resistance mechanisms in Pseudomonas aeruginosa clinical isolates

    PubMed Central

    Charretier, Yannick; Köhler, Thilo; Cecchini, Tiphaine; Bardet, Chloé; Cherkaoui, Abdessalam; Llanes, Catherine; Bogaerts, Pierre; Chatellier, Sonia; Charrier, Jean-Philippe; Schrenzel, Jacques

    2015-01-01

    Both acquired and intrinsic mechanisms play a crucial role in Pseudomonas aeruginosa antibiotic resistance. Many clinically relevant resistance mechanisms result from changes in gene expression, namely multidrug efflux pump overproduction, AmpC β-lactamase induction or derepression, and inactivation or repression of the carbapenem-specific porin OprD. Changes in gene expression are usually assessed using reverse-transcription quantitative real-time PCR (RT-qPCR) assays. Here, we evaluated label-free Selected Reaction Monitoring (SRM)-based mass spectrometry to directly quantify proteins involved in antibiotic resistance. We evaluated the label-free SRM using a defined set of P. aeruginosa isolates with known resistance mechanisms and compared it with RT-qPCR. Referring to efflux systems, we found a more robust relative quantification of antibiotic resistance mechanisms by SRM than RT-qPCR. The SRM-based approach was applied to a set of clinical P. aeruginosa isolates to detect antibiotic resistance proteins. This multiplexed SRM-based approach is a rapid and reliable method for the simultaneous detection and quantification of resistance mechanisms and we demonstrate its relevance for antibiotic resistance prediction. PMID:25713571

  14. The Complex Relationship between Virulence and Antibiotic Resistance

    PubMed Central

    Schroeder, Meredith; Brooks, Benjamin D.; Brooks, Amanda E.

    2017-01-01

    Antibiotic resistance, prompted by the overuse of antimicrobial agents, may arise from a variety of mechanisms, particularly horizontal gene transfer of virulence and antibiotic resistance genes, which is often facilitated by biofilm formation. The importance of phenotypic changes seen in a biofilm, which lead to genotypic alterations, cannot be overstated. Irrespective of if the biofilm is single microbe or polymicrobial, bacteria, protected within a biofilm from the external environment, communicate through signal transduction pathways (e.g., quorum sensing or two-component systems), leading to global changes in gene expression, enhancing virulence, and expediting the acquisition of antibiotic resistance. Thus, one must examine a genetic change in virulence and resistance not only in the context of the biofilm but also as inextricably linked pathologies. Observationally, it is clear that increased virulence and the advent of antibiotic resistance often arise almost simultaneously; however, their genetic connection has been relatively ignored. Although the complexities of genetic regulation in a multispecies community may obscure a causative relationship, uncovering key genetic interactions between virulence and resistance in biofilm bacteria is essential to identifying new druggable targets, ultimately providing a drug discovery and development pathway to improve treatment options for chronic and recurring infection. PMID:28106797

  15. Genetic Regulation of Virulence and Antibiotic Resistance in Acinetobacter baumannii

    PubMed Central

    Kröger, Carsten; Kary, Stefani C.; Schauer, Kristina; Cameron, Andrew D. S.

    2016-01-01

    Multidrug resistant microorganisms are forecast to become the single biggest challenge to medical care in the 21st century. Over the last decades, members of the genus Acinetobacter have emerged as bacterial opportunistic pathogens, in particular as challenging nosocomial pathogens because of the rapid evolution of antimicrobial resistances. Although we lack fundamental biological insight into virulence mechanisms, an increasing number of researchers are working to identify virulence factors and to study antibiotic resistance. Here, we review current knowledge regarding the regulation of virulence genes and antibiotic resistance in Acinetobacter baumannii. A survey of the two-component systems AdeRS, BaeSR, GacSA and PmrAB explains how each contributes to antibiotic resistance and virulence gene expression, while BfmRS regulates cell envelope structures important for pathogen persistence. A. baumannii uses the transcription factors Fur and Zur to sense iron or zinc depletion and upregulate genes for metal scavenging as a critical survival tool in an animal host. Quorum sensing, nucleoid-associated proteins, and non-classical transcription factors such as AtfA and small regulatory RNAs are discussed in the context of virulence and antibiotic resistance. PMID:28036056

  16. Multidrug efflux pumps as main players in intrinsic and acquired resistance to antimicrobials.

    PubMed

    Hernando-Amado, Sara; Blanco, Paula; Alcalde-Rico, Manuel; Corona, Fernando; Reales-Calderón, Jose A; Sánchez, María B; Martínez, José L

    2016-09-01

    Multidrug efflux pumps constitute a group of transporters that are ubiquitously found in any organism. In addition to other functions with relevance for the cell physiology, efflux pumps contribute to the resistance to compounds used for treating different diseases, including resistance to anticancer drugs, antibiotics or antifungal compounds. In the case of antimicrobials, efflux pumps are major players in both intrinsic and acquired resistance to drugs currently in use for the treatment of infectious diseases. One important aspect not fully explored of efflux pumps consists on the identification of effectors able to induce their expression. Indeed, whereas the analysis of clinical isolates have shown that mutants overexpressing these resistance elements are frequently found, less is known on the conditions that may trigger expression of efflux pumps, hence leading to transient induction of resistance in vivo, a situation that is barely detectable using classical susceptibility tests. In the current article we review the structure and mechanisms of regulation of the expression of bacterial and fungal efflux pumps, with a particular focus in those for which a role in clinically relevant resistance has been reported.

  17. Molecular basis of NDM-1, a new antibiotic resistance determinant.

    PubMed

    Liang, Zhongjie; Li, Lianchun; Wang, Yuanyuan; Chen, Limin; Kong, Xiangqian; Hong, Yao; Lan, Lefu; Zheng, Mingyue; Guang-Yang, Cai; Liu, Hong; Shen, Xu; Luo, Cheng; Li, Keqin Kathy; Chen, Kaixian; Jiang, Hualiang

    2011-01-01

    The New Delhi Metallo-β-lactamase (NDM-1) was first reported in 2009 in a Swedish patient. A recent study reported that Klebsiella pneumonia NDM-1 positive strain or Escherichia coli NDM-1 positive strain was highly resistant to all antibiotics tested except tigecycline and colistin. These can no longer be relied on to treat infections and therefore, NDM-1 now becomes potentially a major global health threat.In this study, we performed modeling studies to obtain its 3D structure and NDM-1/antibiotics complex. It revealed that the hydrolytic mechanisms are highly conserved. In addition, the detailed analysis indicates that the more flexible and hydrophobic loop1, together with the evolution of more positive-charged loop2 leads to NDM-1 positive strain more potent and extensive in antibiotics resistance compared with other MBLs. Furthermore, through biological experiments, we revealed the molecular basis for antibiotics catalysis of NDM-1 on the enzymatic level. We found that NDM-1 enzyme was highly potent to degrade carbapenem antibiotics, while mostly susceptible to tigecycline, which had the ability to slow down the hydrolysis velocity of meropenem by NDM-1. Meanwhile, the mutagenesis experiments, including D124A, C208A, K211A and K211E, which displayed down-regulation on meropenem catalysis, proved the accuracy of our model.At present, there are no effective antibiotics against NDM-1 positive pathogen. Our study will provide clues to investigate the molecular basis of extended antibiotics resistance of NDM-1 and then accelerate the search for new antibiotics against NDM-1 positive strain in clinical studies.

  18. Sensitivity and resistance of Legionella pneumophila to some antibiotics and combinations of antibiotics.

    PubMed

    Moffie, B G; Mouton, R P

    1988-10-01

    For the treatment of Legionella pneumophila infections erythromycin and rifampicin are the antibiotics of choice. In view of reported therapy failures other antibiotics, e.g. the quinolones, are currently under investigation. The sensitivity of L. pneumophila to four antibiotics and to combinations of antibiotics was investigated and the rate of mutations was calculated. For 20 L. pneumophila strains we determined the MIC of rifampicin (0.002-0.004 mg/l), erythromycin (0.063-0.125 mg/l), norfloxacin (0.125 mg/l) and ciprofloxacin (0.016-0.032 mg/l). Mutation rates ranged from 1 x 10(-8) for ciprofloxacin to greater than 1 x 10(-7) for erythromycin, resulting in high-level resistance to rifampicin in most strains and erythromycin resistance in one strain, but not in resistance to the quinolones. The combination of erythromycin and rifampicin was synergistic (FIC index less than 0.5) against four of the L. pneumophila strains and showed indifference (FIC index 0.5-2.0) for the remainder (mean FIC index 0.79). Combinations of ciprofloxacin and erythromycin and of rifampicin and ciprofloxacin showed only indifference (mean FIC index respectively 1.05 and 1.21). Combining rifampicin with ciprofloxacin was not effective in reducing the number of mutants for either of these antibiotics, whereas the other combinations did prevent this.

  19. Contribution of phenotypic heterogeneity to adaptive antibiotic resistance

    PubMed Central

    Sánchez-Romero, María Antonia; Casadesús, Josep

    2014-01-01

    Antibiotic-resistant isolates of Salmonella enterica were selected on plates containing lethal concentrations of rifampicin, kanamycin, and nalidixic acid. The stability of the resistance phenotype was scored after nonselective growth. Rifampicin-resistant (Rifr) isolates were stable, suggesting that they had arisen by mutation. Mutations in the rpoB gene were detected indeed in Rifr mutants. In contrast, a fraction of kanamycin-resistant (Kmr) and nalidixic acid-resistant (Nalr) isolates showed reduced resistance after nonselective growth, suggesting that mechanisms other than mutation had contributed to bacterial survival upon lethal selection. Single-cell analysis revealed heterogeneity in expression of the porin gene ompC, and subpopulation separation provided evidence that reduced ompC expression confers adaptive resistance to kanamycin. In the case of Nalr isolates, mutations in the gyrA gene were present in most nalidixic acid-resistant isolates. However, the efflux pump inhibitor Phe-Arg-β-naphtylamide (PAβN) reduced the level of resistance in Nalr mutants, indicating that active efflux contributes to the overall level of nalidixic acid resistance. Heterogeneous efflux pump activity was detected in single cells and colonies, and a correlation between high efflux and increased resistance to nalidixic acid was found. These observations suggest that fluctuations in the expression and the activity of critical functions of the bacterial cell, alone or combined with mutations, can contribute to adaptive resistance to antibiotics. PMID:24351930

  20. Contribution of phenotypic heterogeneity to adaptive antibiotic resistance.

    PubMed

    Sánchez-Romero, María Antonia; Casadesús, Josep

    2014-01-07

    Antibiotic-resistant isolates of Salmonella enterica were selected on plates containing lethal concentrations of rifampicin, kanamycin, and nalidixic acid. The stability of the resistance phenotype was scored after nonselective growth. Rifampicin-resistant (Rif(r)) isolates were stable, suggesting that they had arisen by mutation. Mutations in the rpoB gene were detected indeed in Rif(r) mutants. In contrast, a fraction of kanamycin-resistant (Km(r)) and nalidixic acid-resistant (Nal(r)) isolates showed reduced resistance after nonselective growth, suggesting that mechanisms other than mutation had contributed to bacterial survival upon lethal selection. Single-cell analysis revealed heterogeneity in expression of the porin gene ompC, and subpopulation separation provided evidence that reduced ompC expression confers adaptive resistance to kanamycin. In the case of Nal(r) isolates, mutations in the gyrA gene were present in most nalidixic acid-resistant isolates. However, the efflux pump inhibitor Phe-Arg-β-naphtylamide (PAβN) reduced the level of resistance in Nal(r) mutants, indicating that active efflux contributes to the overall level of nalidixic acid resistance. Heterogeneous efflux pump activity was detected in single cells and colonies, and a correlation between high efflux and increased resistance to nalidixic acid was found. These observations suggest that fluctuations in the expression and the activity of critical functions of the bacterial cell, alone or combined with mutations, can contribute to adaptive resistance to antibiotics.

  1. Toward a quantitative understanding of antibiotic resistance evolution.

    PubMed

    Lukačišinová, Marta; Bollenbach, Tobias

    2017-03-11

    The rising prevalence of antibiotic resistant bacteria is an increasingly serious public health challenge. To address this problem, recent work ranging from clinical studies to theoretical modeling has provided valuable insights into the mechanisms of resistance, its emergence and spread, and ways to counteract it. A deeper understanding of the underlying dynamics of resistance evolution will require a combination of experimental and theoretical expertise from different disciplines and new technology for studying evolution in the laboratory. Here, we review recent advances in the quantitative understanding of the mechanisms and evolution of antibiotic resistance. We focus on key theoretical concepts and new technology that enables well-controlled experiments. We further highlight key challenges that can be met in the near future to ultimately develop effective strategies for combating resistance.

  2. Efforts to slacken antibiotic resistance: Labeling meat products from animals raised without antibiotics in the United States.

    PubMed

    Centner, Terence J

    2016-09-01

    As bacteria and diseases spread due to climatic change, greater amounts of antibiotics will be used thereby exacerbating the problem of antibiotic resistance. To help slacken the development of resistant bacteria, the medical community is attempting to reduce unnecessary and excessive usage of antibiotics. One of the targets is the use of antibiotics for enhancing animal growth and promoting feed efficiency in the production of food animals. While governments can adopt regulations prohibiting nontherapeutic uses of antibiotics in food animals and strategies to reduce antibiotic usage, another idea is to publicize when antibiotics are used in food animal production by allowing labeled meat products. This paper builds upon existing labeling and marketing efforts in the United States to show how a government can develop a verified antibiotic-free labeling program that would allow consumers to purchase meat products from animals that had never received antibiotics.

  3. Bacteriophage therapy: a potential solution for the antibiotic resistance crisis.

    PubMed

    Golkar, Zhabiz; Bagasra, Omar; Pace, Donald Gene

    2014-02-13

    The emergence of multiple drug-resistant bacteria has prompted interest in alternatives to conventional antimicrobials. One of the possible replacement options for antibiotics is the use of bacteriophages as antimicrobial agents. Phage therapy is an important alternative to antibiotics in the current era of drug-resistant pathogens. Bacteriophages have played an important role in the expansion of molecular biology and have been used as antibacterial agents since 1966. In this review, we describe a brief history of bacteriophages and clinical studies on their use in bacterial disease prophylaxis and therapy. We discuss the advantages and disadvantages of bacteriophages as therapeutic agents in this regard.

  4. Prevalence of antibiotic-resistant E. coli in retail chicken: comparing conventional, organic, kosher, and raised without antibiotics.

    PubMed

    Millman, Jack M; Waits, Kara; Grande, Heidi; Marks, Ann R; Marks, Jane C; Price, Lance B; Hungate, Bruce A

    2013-01-01

    Retail poultry products are known sources of antibiotic-resistant Escherichia coli, a major human health concern. Consumers have a range of choices for poultry, including conventional, organic, kosher, and raised without antibiotics (RWA) - designations that are perceived to indicate differences in quality and safety. However, whether these categories vary in the frequency of contamination with antibiotic-resistant E. coli is unknown. We examined the occurrence of antibiotic-resistant E. coli on raw chicken marketed as conventional, organic, kosher and RWA. From April - June 2012, we purchased 213 samples of raw chicken from 15 locations in the New York City metropolitan area. We screened E. coli isolates from each sample for resistance to 12 common antibiotics. Although the organic and RWA labels restrict the use of antibiotics, the frequency of antibiotic-resistant E. coli tended to be only slightly lower for RWA, and organic chicken was statistically indistinguishable from conventional products that have no restrictions. Kosher chicken had the highest frequency of antibiotic-resistant E. coli, nearly twice that of conventional products, a result that belies the historical roots of kosher as a means to ensure food safety. These results indicate that production methods influence the frequency of antibiotic-resistant E. coli on poultry products available to consumers. Future research to identify the specific practices that cause the high frequency of antibiotic-resistant E. coli in kosher chicken could promote efforts to reduce consumer exposure to this potential pathogen.

  5. Prevalence of antibiotic-resistant E. coli in retail chicken: comparing conventional, organic, kosher, and raised without antibiotics

    PubMed Central

    Price, Lance B; Hungate, Bruce A

    2013-01-01

    Retail poultry products are known sources of antibiotic-resistant Escherichia coli, a major human health concern. Consumers have a range of choices for poultry, including conventional, organic, kosher, and raised without antibiotics (RWA) – designations that are perceived to indicate differences in quality and safety. However, whether these categories vary in the frequency of contamination with antibiotic-resistant E. coli is unknown. We examined the occurrence of antibiotic-resistant E. coli on raw chicken marketed as conventional, organic, kosher and RWA. From April – June 2012, we purchased 213 samples of raw chicken from 15 locations in the New York City metropolitan area. We screened E. coli isolates from each sample for resistance to 12 common antibiotics. Although the organic and RWA labels restrict the use of antibiotics, the frequency of antibiotic-resistant E. coli tended to be only slightly lower for RWA, and organic chicken was statistically indistinguishable from conventional products that have no restrictions. Kosher chicken had the highest frequency of antibiotic-resistant E. coli, nearly twice that of conventional products, a result that belies the historical roots of kosher as a means to ensure food safety. These results indicate that production methods influence the frequency of antibiotic-resistant E. coli on poultry products available to consumers. Future research to identify the specific practices that cause the high frequency of antibiotic-resistant E. coli in kosher chicken could promote efforts to reduce consumer exposure to this potential pathogen. PMID:24555073

  6. Development and characterisation of highly antibiotic resistant Bartonella bacilliformis mutants

    PubMed Central

    Gomes, Cláudia; Martínez-Puchol, Sandra; Ruiz-Roldán, Lidia; Pons, Maria J.; del Valle Mendoza, Juana; Ruiz, Joaquim

    2016-01-01

    The objective was to develop and characterise in vitro Bartonella bacilliformis antibiotic resistant mutants. Three B. bacilliformis strains were plated 35 or 40 times with azithromycin, chloramphenicol, ciprofloxacin or rifampicin discs. Resistance-stability was assessed performing 5 serial passages without antibiotic pressure. MICs were determined with/without Phe-Arg-β-Napthylamide and artesunate. Target alterations were screened in the 23S rRNA, rplD, rplV, gyrA, gyrB, parC, parE and rpoB genes. Chloramphenicol and ciprofloxacin resistance were the most difficult and easiest (>37.3 and 10.6 passages) to be selected, respectively. All mutants but one selected with chloramphenicol achieved high resistance levels. All rifampicin, one azithromycin and one ciprofloxacin mutants did not totally revert when cultured without antibiotic pressure. Azithromycin resistance was related to L4 substitutions Gln-66 → Lys or Gly-70 → Arg; L4 deletion Δ62–65 (Lys-Met-Tyr-Lys) or L22 insertion 83::Val-Ser-Glu-Ala-His-Val-Gly-Lys-Ser; in two chloramphenicol-resistant mutants the 23S rRNA mutation G2372A was detected. GyrA Ala-91 → Val and Asp-95 → Gly and GyrB Glu474 → Lys were detected in ciprofloxacin-resistant mutants. RpoB substitutions Gln-527 → Arg, His-540 → Tyr and Ser-545 → Phe plus Ser-588 → Tyr were detected in rifampicin-resistant mutants. In 5 mutants the effect of efflux pumps on resistance was observed. Antibiotic resistance was mainly related to target mutations and overexpression of efflux pumps, which might underlie microbiological failures during treatments. PMID:27667026

  7. Development and characterisation of highly antibiotic resistant Bartonella bacilliformis mutants.

    PubMed

    Gomes, Cláudia; Martínez-Puchol, Sandra; Ruiz-Roldán, Lidia; Pons, Maria J; Del Valle Mendoza, Juana; Ruiz, Joaquim

    2016-09-26

    The objective was to develop and characterise in vitro Bartonella bacilliformis antibiotic resistant mutants. Three B. bacilliformis strains were plated 35 or 40 times with azithromycin, chloramphenicol, ciprofloxacin or rifampicin discs. Resistance-stability was assessed performing 5 serial passages without antibiotic pressure. MICs were determined with/without Phe-Arg-β-Napthylamide and artesunate. Target alterations were screened in the 23S rRNA, rplD, rplV, gyrA, gyrB, parC, parE and rpoB genes. Chloramphenicol and ciprofloxacin resistance were the most difficult and easiest (>37.3 and 10.6 passages) to be selected, respectively. All mutants but one selected with chloramphenicol achieved high resistance levels. All rifampicin, one azithromycin and one ciprofloxacin mutants did not totally revert when cultured without antibiotic pressure. Azithromycin resistance was related to L4 substitutions Gln-66 → Lys or Gly-70 → Arg; L4 deletion Δ62-65 (Lys-Met-Tyr-Lys) or L22 insertion 83::Val-Ser-Glu-Ala-His-Val-Gly-Lys-Ser; in two chloramphenicol-resistant mutants the 23S rRNA mutation G2372A was detected. GyrA Ala-91 → Val and Asp-95 → Gly and GyrB Glu474 → Lys were detected in ciprofloxacin-resistant mutants. RpoB substitutions Gln-527 → Arg, His-540 → Tyr and Ser-545 → Phe plus Ser-588 → Tyr were detected in rifampicin-resistant mutants. In 5 mutants the effect of efflux pumps on resistance was observed. Antibiotic resistance was mainly related to target mutations and overexpression of efflux pumps, which might underlie microbiological failures during treatments.

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

    PubMed

    Coelho, Tatiane; Machado, Diana; Couto, Isabel; Maschmann, Raquel; Ramos, Daniela; von Groll, Andrea; Rossetti, Maria L; Silva, Pedro A; Viveiros, Miguel

    2015-01-01

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

  9. Inappropriate use of antibiotics in hospitals: the complex relationship between antibiotic use and antimicrobial resistance.

    PubMed

    Cantón, Rafael; Horcajada, Juan Pablo; Oliver, Antonio; Garbajosa, Patricia Ruiz; Vila, Jordi

    2013-09-01

    Hospitals are considered an excellent compartment for the selection of resistant and multi-drug resistant (MDR) bacteria. The overuse and misuse of antimicrobial agents are considered key points fuelling this situation. Antimicrobial stewardship programs have been designed for better use of these compounds to prevent the emergence of resistant microorganisms and to diminish the upward trend in resistance. Nevertheless, the relationship between antibiotic use and antimicrobial resistance is complex, and the desired objectives are difficult to reach. Various factors affecting this relationship have been advocated including, among others, antibiotic exposure and mutant selection windows, antimicrobial pharmacodynamics, the nature of the resistance (natural or acquired, including mutational and that associated with horizontal gene transfer) and the definition of resistance. Moreover, antimicrobial policies to promote better use of these drugs should be implemented not only in the hospital setting coupled with infection control programs, but also in the community, which should also include animal and environmental compartments. Within hospitals, the restriction of antimicrobials, cycling and mixing strategies and the use of combination therapies have been used to avoid resistance. Nevertheless, the results have not always been favorable and resistant bacteria have persisted despite the theoretical benefits of these strategies. Mathematical models as well as microbiological knowledge can explain this failure, which is mainly related to the current scenario involving MDR bacteria and overcoming the fitness associated with resistance. New antimicrobials, rapid diagnostic and antimicrobial susceptibility testing and biomarkers will be useful for future antimicrobial stewardship interventions.

  10. Is household antibiotic use a risk factor for antibiotic-resistant pneumococcal infection?

    PubMed Central

    Kwan-Gett, T. S.; Davis, R. L.; Shay, D. K.; Black, S.; Shinefield, H.; Koepsell, T.

    2002-01-01

    We used microbiology and pharmacy data from health-maintenance organizations to determine whether antibiotic use by a household member increases the risk of penicillin-non-susceptible pneumococcal disease. Though it has been well established that an individual's antibiotic use increases one's risk of antibiotic-resistant infection, it is unclear whether the risk is increased if a member of one's household is exposed to antibiotics. We therefore conducted a case-control study of patients enrolled in health maintenance organizations in Western Washington and Northern California. Cases were defined as individuals with penicillin-non-susceptible pneumococcal infection; controls were individuals with penicillin-susceptible pneumococcal infection. Socioeconomic variables were obtained by linking addresses with 1997 census block group data. One-hundred and thirty-four cases were compared with 798 controls. Individual antibiotic use prior to diagnosis increased the odds of penicillin non-susceptibility, with the strongest effect seen for beta-lactam use within 2 months (OR 1.8, 95% CI 1.2, 2.8). When household antibiotic use by persons other than the patient were considered, at 4 months prior to diagnosis there was a trend towards an association between penicillin non-susceptibility and beta-lactam antibiotic use, and a possible association in a small subgroup of patients with eye and ear isolates. However, no significant overall pattern of association was seen. We conclude that though antibiotic use of any kind within 2 months prior to diagnosis is associated with an increased risk of penicillin-non-susceptible pneumococcal disease, there is no significant overall pattern of association between household antibiotic use and penicillin-non-susceptible pneumococcal infection. PMID:12558332

  11. FARME DB: a functional antibiotic resistance element database

    PubMed Central

    Wallace, James C.; Port, Jesse A.; Smith, Marissa N.; Faustman, Elaine M.

    2017-01-01

    Antibiotic resistance (AR) is a major global public health threat but few resources exist that catalog AR genes outside of a clinical context. Current AR sequence databases are assembled almost exclusively from genomic sequences derived from clinical bacterial isolates and thus do not include many microbial sequences derived from environmental samples that confer resistance in functional metagenomic studies. These environmental metagenomic sequences often show little or no similarity to AR sequences from clinical isolates using standard classification criteria. In addition, existing AR databases provide no information about flanking sequences containing regulatory or mobile genetic elements. To help address this issue, we created an annotated database of DNA and protein sequences derived exclusively from environmental metagenomic sequences showing AR in laboratory experiments. Our Functional Antibiotic Resistant Metagenomic Element (FARME) database is a compilation of publically available DNA sequences and predicted protein sequences conferring AR as well as regulatory elements, mobile genetic elements and predicted proteins flanking antibiotic resistant genes. FARME is the first database to focus on functional metagenomic AR gene elements and provides a resource to better understand AR in the 99% of bacteria which cannot be cultured and the relationship between environmental AR sequences and antibiotic resistant genes derived from cultured isolates. Database URL: http://staff.washington.edu/jwallace/farme PMID:28077567

  12. Perturbation of iron homeostasis promotes the evolution of antibiotic resistance.

    PubMed

    Méhi, Orsolya; Bogos, Balázs; Csörgő, Bálint; Pál, Ferenc; Nyerges, Akos; Papp, Balázs; Pál, Csaba

    2014-10-01

    Evolution of antibiotic resistance in microbes is frequently achieved by acquisition of spontaneous mutations during antimicrobial therapy. Here, we demonstrate that inactivation of a central transcriptional regulator of iron homeostasis (Fur) facilitates laboratory evolution of ciprofloxacin resistance in Escherichia coli. To decipher the underlying molecular mechanisms, we first performed a global transcriptome analysis and demonstrated that the set of genes regulated by Fur changes substantially in response to antibiotic treatment. We hypothesized that the impact of Fur on evolvability under antibiotic pressure is due to the elevated intracellular concentration of free iron and the consequent enhancement of oxidative damage-induced mutagenesis. In agreement with expectations, overexpression of iron storage proteins, inhibition of iron transport, or anaerobic conditions drastically suppressed the evolution of resistance, whereas inhibition of the SOS response-mediated mutagenesis had only a minor effect. Finally, we provide evidence that a cell permeable iron chelator inhibits the evolution of resistance. In sum, our work revealed the central role of iron metabolism in the de novo evolution of antibiotic resistance, a pattern that could influence the development of novel antimicrobial strategies.

  13. Helicobacter pylori and Antibiotic Resistance, A Continuing and Intractable Problem.

    PubMed

    Hu, Yue; Zhang, Meng; Lu, Bin; Dai, Jinfeng

    2016-10-01

    Helicobacter pylori, a human pathogen with a high global prevalence, is the causative pathogen for multiple gastrointestinal diseases, especially chronic gastritis, peptic ulcers, gastric mucosa-associated lymphoid tissue lymphoma, and gastric malignancies. Antibiotic therapies remain the mainstay for H. pylori eradication; however, this strategy is hampered by the emergence and spread of H. pylori antibiotic resistance. Exploring the mechanistic basis of this resistance is becoming one of the major research questions in contemporary biomedical research, as such knowledge could be exploited to devise novel rational avenues for counteracting the existing resistance and devising strategies to avoid the development of a novel anti-H. pylori medication. Encouragingly, important progress in this field has been made recently. Here, we attempt to review the current state and progress with respect to the molecular mechanism of antibiotic resistance for H. pylori. A picture is emerging in which mutations of various genes in H. pylori, resulting in decreased membrane permeability, altered oxidation-reduction potential, and a more efficient efflux pump system. The increased knowledge on these mechanisms produces hope that antibiotic resistance in H. pylori can ultimately be countered.

  14. Effect of river landscape on the sediment concentrations of antibiotics and corresponding antibiotic resistance genes (ARG).

    PubMed

    Pei, Ruoting; Kim, Sung-Chul; Carlson, Kenneth H; Pruden, Amy

    2006-07-01

    The purpose of this study was to quantify antibiotic resistance genes (ARG) in the sediments of the mixed-landscape Cache La Poudre River, which has previously been studied and shown to have high concentrations of antibiotics related to urban and agricultural activities. River sediments were sampled during two events (high-flow and low-flow) from five sites with varying urban and agricultural impact levels. Polymerase-chain-reaction (PCR) detection assays were conducted for four sulfonamide resistance gene families, using newly designed primers, and five tetracycline resistance gene families, using previously published primers. Sul(I), sul(II), tet(W), and tet(O) gene families were further quantified by real-time quantitative polymerase chain reaction (Q-PCR). Resistance to four classes of antibiotics (tetracyclines, sulfonamides, ionophores, and macrolides) was also investigated using a culture-based approach. The quantities of resistance genes normalized to the 16S gene copy number were significantly different between the sites, with higher resistance gene concentrations at the impacted sites than at the pristine site. Total resistant CFUs were over an order of magnitude lower at the pristine site, but differences were less apparent when normalized to the total CFUs. Six tetracyclines and six sulfonamides were also quantified in the sediments and were found to be highest at sites impacted by urban and agricultural activity, with no antibiotics detected at the pristine sit. To the knowledge of the authors, this study is the first to demonstrate a relationship between urban and agricultural activity and microbial resistance in river sediments using quantitative molecular tools.

  15. Monopoly pricing of an antibiotic subject to bacterial resistance.

    PubMed

    Herrmann, Markus

    2010-01-01

    We develop a dynamic bio-economic model of bacterial resistance and disease transmission in which we characterize the pricing policy of a monopolist who is protected by a patent. After expiration, the monopolist behaves competitively in a generic industry having open access to the common pool of antibiotic efficacy and infection. The monopolist manages endogenously the levels of antibiotic efficacy as well as the infected population, which represent quality and market size respectively and achieves, at least temporarily, higher such levels than a hypothetically myopic monopolist who does not take into account the dynamic externalities. The pricing policy and the biological system is characterized by the turnpike property. Before the patent vanishes, the monopolist behaves more and more myopically, leading to a continuous decrease in the price of the antibiotic. Once the generic industry takes over, a discontinuous fall in price occurs. Whether a prolongation of the patent is socially desirable depends on the relative levels of antibiotic efficacy and infection.

  16. Multidrug Efflux Pumps at the Crossroad between Antibiotic Resistance and Bacterial Virulence

    PubMed Central

    Alcalde-Rico, Manuel; Hernando-Amado, Sara; Blanco, Paula; Martínez, José L.

    2016-01-01

    Multidrug efflux pumps can be involved in bacterial resistance to antibiotics at different levels. Some efflux pumps are constitutively expressed at low levels and contribute to intrinsic resistance. In addition, their overexpression may allow higher levels of resistance. This overexpression can be transient, in the presence of an effector (phenotypic resistance), or constitutive when mutants in the regulatory elements of the expression of efflux pumps are selected (acquired resistance). Efflux pumps are present in all cells, from human to bacteria and are highly conserved, which indicates that they are ancient elements in the evolution of different organisms. Consequently, it has been suggested that, besides antibiotic resistance, bacterial multidrug efflux pumps would likely contribute to other relevant processes of the microbial physiology. In the current article, we discuss some specific examples of the role that efflux pumps may have in the bacterial virulence of animals’ and plants’ pathogens, including the processes of intercellular communication. Based in these evidences, we propose that efflux pumps are at the crossroad between resistance and virulence of bacterial pathogens. Consequently, the comprehensive study of multidrug efflux pumps requires addressing these functions, which are of relevance for the bacterial–host interactions during infection. PMID:27708632

  17. Multidrug Efflux Pumps at the Crossroad between Antibiotic Resistance and Bacterial Virulence.

    PubMed

    Alcalde-Rico, Manuel; Hernando-Amado, Sara; Blanco, Paula; Martínez, José L

    2016-01-01

    Multidrug efflux pumps can be involved in bacterial resistance to antibiotics at different levels. Some efflux pumps are constitutively expressed at low levels and contribute to intrinsic resistance. In addition, their overexpression may allow higher levels of resistance. This overexpression can be transient, in the presence of an effector (phenotypic resistance), or constitutive when mutants in the regulatory elements of the expression of efflux pumps are selected (acquired resistance). Efflux pumps are present in all cells, from human to bacteria and are highly conserved, which indicates that they are ancient elements in the evolution of different organisms. Consequently, it has been suggested that, besides antibiotic resistance, bacterial multidrug efflux pumps would likely contribute to other relevant processes of the microbial physiology. In the current article, we discuss some specific examples of the role that efflux pumps may have in the bacterial virulence of animals' and plants' pathogens, including the processes of intercellular communication. Based in these evidences, we propose that efflux pumps are at the crossroad between resistance and virulence of bacterial pathogens. Consequently, the comprehensive study of multidrug efflux pumps requires addressing these functions, which are of relevance for the bacterial-host interactions during infection.

  18. Fungal Resistance to Plant Antibiotics as a Mechanism of Pathogenesis

    PubMed Central

    Morrissey, John P.; Osbourn, Anne E.

    1999-01-01

    Many plants produce low-molecular-weight compounds which inhibit the growth of phytopathogenic fungi in vitro. These compounds may be preformed inhibitors that are present constitutively in healthy plants (also known as phytoanticipins), or they may be synthesized in response to pathogen attack (phytoalexins). Successful pathogens must be able to circumvent or overcome these antifungal defenses, and this review focuses on the significance of fungal resistance to plant antibiotics as a mechanism of pathogenesis. There is increasing evidence that resistance of fungal pathogens to plant antibiotics can be important for pathogenicity, at least for some fungus-plant interactions. This evidence has emerged largely from studies of fungal degradative enzymes and also from experiments in which plants with altered levels of antifungal secondary metabolites were generated. Whereas the emphasis to date has been on degradative mechanisms of resistance of phytopathogenic fungi to antifungal secondary metabolites, in the future we are likely to see a rapid expansion in our knowledge of alternative mechanisms of resistance. These may include membrane efflux systems of the kind associated with multidrug resistance and innate resistance due to insensitivity of the target site. The manipulation of plant biosynthetic pathways to give altered antibiotic profiles will also be valuable in telling us more about the significance of antifungal secondary metabolites for plant defense and clearly has great potential for enhancing disease resistance for commercial purposes. PMID:10477313

  19. Identification of intrinsically metronidazole-resistant clades of Gardnerella vaginalis.

    PubMed

    Schuyler, Jessica A; Mordechai, Eli; Adelson, Martin E; Sobel, Jack D; Gygax, Scott E; Hilbert, David W

    2016-01-01

    Gardnerella vaginalis is associated with bacterial vaginosis (BV), the most common cause of vaginal discharge. Metronidazole is a front-line therapy for BV, and treatment failure and recurrent disease are common problems. Whole-genome sequencing studies have revealed that G. vaginalis has a population structure that consists of 4 clades: clades 1 and 3 are associated with BV, whereas clades 2 and 4 are not. To determine if metronidazole susceptibility is associated with population structure, we analyzed 87 clinical isolates and found that metronidazole resistance (MIC ≥32 μg/mL) was highly associated with clade (P<0.0001), as 14/14 clade 3 isolates (100%) and 22/22 clade 4 isolates (100%) exhibited resistance, compared to only 16/37 clade 1 isolates (35%) and 1/14 clade 2 isolates (7.1%). The identification of intrinsically metronidazole-resistant G. vaginalis clades will facilitate future studies on the relationship between metronidazole resistance and BV treatment failure.

  20. Bacteriology and antibiotic resistance in chronic rhinosinusitis.

    PubMed

    Manes, R Peter; Batra, Pete S

    2012-02-01

    Chronic rhinosinusitis (CRS) is a prevalent health care problem that may be commonly encountered in patients desiring aesthetic or reconstructive rhinoplasty. The purpose of this article is to review the common bacterial pathogens associated with CRS, as well as patterns of bacterial resistance in this patient subset. Close understanding of microbial pathogens involved in CRS and their associated resistance patterns will guide facial plastic surgeons in optimally managing this important potential comorbidity, and in turn positively influence the outcome of rhinoplasty.

  1. Antibiotic-resistant acne: getting under the skin.

    PubMed

    Sinha, Mau; Sadhasivam, Suresh; Bhattacharyya, Anamika; Jain, Shilpi; Ghosh, Shamik; Arndt, Kenneth A; Dover, Jeffrey S; Sengupta, Shiladitya

    2016-06-01

    Propionibacterium acnes is a key pathogenic factor in the development of acne. Antibiotics are the first choice of treatment for mild-to-moderate, mixed, papular/pustular, and moderate nodular acne, and an alternative choice in severe, nodular/conglobate acne. The emergence of resistance to the currently available antibiotics poses a serious set-back to this algorithm, and the reduced arsenal can diminish efficacy of treatment. This emerging situation should catalyze innovations in dermatology; for example, newer drugs and technologies such as next-generation antibiotics with excellent potency and low propensity to develop resistance, rapid diagnostic platforms to select responders and nonresponders, and delivery technologies that target the bacteria. Such innovations can dramatically expand the arsenal for dermatologists in the management of acne.

  2. Beta-lactam Antibiotics: From Antibiosis to Resistance and Bacteriology

    PubMed Central

    Kong, Kok-Fai; Schneper, Lisa; Mathee, Kalai

    2010-01-01

    SUMMARY This review focuses on the era of antibiosis that led to a better understanding of bacterial morphology, in particlar the cell wall component peptidoglycan. This is an effort to take readers on a tour de force from the concept of antibiosis, to the serepidity of antibiotics, evolution of beta-lactam development, and the molecular biology of antibiotic resistance. These areas of research have culminated in a deeper understanding of microbiology, particularly in the area of bacterial cell wall synthesis and recycling. In spite of this knowledge, which has enabled design of new even more effective therapeutics to combat bacterial infection and has provided new research tools, antibiotic resistance remains a worldwide health care problem. PMID:20041868

  3. Why is antibiotic resistance a deadly emerging disease?

    PubMed

    Courvalin, P

    2016-05-01

    Evolution of bacteria towards resistance to antimicrobial agents, including multidrug resistance, is unavoidable because it represents a particular aspect of the general evolution of bacteria that is unstoppable. Therefore, the only means of dealing with this situation is to delay the emergence and subsequent dissemination of resistant bacteria or resistance genes. In this review, we will consider the biochemical mechanisms and the genetics that bacteria use to offset antibiotic selective pressure. The data provided are mainly, if not exclusively, taken from the work carried out in the laboratory, although there are numerous other examples in the literature.

  4. Persistence of antibiotic resistance: evaluation of a probiotic approach using antibiotic-sensitive Megasphaera elsdenii strains to prevent colonization of swine by antibiotic-resistant strains.

    PubMed

    Stanton, Thad B; Humphrey, Samuel B

    2011-10-01

    Megasphaera elsdenii is a lactate-fermenting, obligately anaerobic bacterium commonly present in the gastrointestinal tracts of mammals, including humans. Swine M. elsdenii strains were previously shown to have high levels of tetracycline resistance (MIC=64 to >256 μg/ml) and to carry mosaic (recombinant) tetracycline resistance genes. Baby pigs inherit intestinal microbiota from the mother sow. In these investigations we addressed two questions. When do M. elsdenii strains from the sow colonize baby pigs? Can five antibiotic-sensitive M. elsdenii strains administered intragastrically to newborn pigs affect natural colonization of the piglets by antibiotic-resistant (AR) M. elsdenii strains from the mother? M. elsdenii natural colonization of newborn pigs was undetectable (<10(4) CFU/g [wet weight] of feces) prior to weaning (20 days after birth). After weaning, all pigs became colonized (4 × 10(5) to 2 × 10(8) CFU/g feces). In a separate study, 61% (76/125) of M. elsdenii isolates from a gravid sow never exposed to antibiotics were resistant to chlortetracycline, ampicillin, or tylosin. The inoculation of the sow's offspring with mixtures of M. elsdenii antibiotic-sensitive strains prevented colonization of the offspring by maternal AR strains until at least 11 days postweaning. At 25 and 53 days postweaning, however, AR strains predominated. Antibiotic susceptibility phenotypes and single nucleotide polymorphism (SNP)-based identities of M. elsdenii isolated from sow and offspring were unexpectedly diverse. These results suggest that dosing newborn piglets with M. elsdenii antibiotic-sensitive strains delays but does not prevent colonization by maternal resistant strains. M. elsdenii subspecies diversity offers an explanation for the persistence of resistant strains in the absence of antibiotic selection.

  5. Molecular Basis for Resistance Against Phosphonate Antibiotics and Herbicides

    PubMed Central

    Chekan, Jonathan R.; Cogan, Dillon P.; Nair, Satish K.

    2015-01-01

    Research in recent years have illuminated data on the mechanisms and targets of phosphonic acid antibiotics and herbicides, including fosfomycin, glyphosate, fosmidomycin and FR900098. Here we review the current state of knowledge of the structural and biochemical characterization of resistance mechanisms against these bioactive natural products. Advances in the understanding of these resistance determinants have spurred knowledge-based campaigns aimed towards the design of derivatives that retain biological activity but are less prone to tolerance. PMID:26811741

  6. Antibiotic Resistant Bacteria--What Everyone Needs To Know.

    ERIC Educational Resources Information Center

    Pascoe, Neil; Felkner, Marilyn; Maldonado, Maria

    2003-01-01

    Notes the overuse of antibiotics and the resulting resistant bacterial strains. Describes how to control and prevent staphylococcal infections specifically, and almost all infectious diseases generally. Specific sections address: (1) what are staph infections; (2) preventing staph infections; (3) caring for wounds; and (4) controlling staph…

  7. Collective Resistance in Microbial Communities by Intracellular Antibiotic Deactivation

    PubMed Central

    Sorg, Robin A.; Lin, Leo; van Doorn, G. Sander; Sorg, Moritz; Olson, Joshua; Nizet, Victor; Veening, Jan-Willem

    2016-01-01

    The structure and composition of bacterial communities can compromise antibiotic efficacy. For example, the secretion of β-lactamase by individual bacteria provides passive resistance for all residents within a polymicrobial environment. Here, we uncover that collective resistance can also develop via intracellular antibiotic deactivation. Real-time luminescence measurements and single-cell analysis demonstrate that the opportunistic human pathogen Streptococcus pneumoniae grows in medium supplemented with chloramphenicol (Cm) when resistant bacteria expressing Cm acetyltransferase (CAT) are present. We show that CAT processes Cm intracellularly but not extracellularly. In a mouse pneumonia model, more susceptible pneumococci survive Cm treatment when coinfected with a CAT-expressing strain. Mathematical modeling predicts that stable coexistence is only possible when antibiotic resistance comes at a fitness cost. Strikingly, CAT-expressing pneumococci in mouse lungs were outcompeted by susceptible cells even during Cm treatment. Our results highlight the importance of the microbial context during infectious disease as a potential complicating factor to antibiotic therapy. PMID:28027306

  8. Stalking Antibiotic-Resistant Bacteria in Common Vegetables

    ERIC Educational Resources Information Center

    Brock, David; Boeke, Caroline; Josowitz, Rebecca; Loya, Katherine

    2004-01-01

    The study developed a simple experimental protocol for studying antibiotic resistant bacteria that will allow students to determine the proportion of such bacteria found on common fruit and vegetable crops. This protocol can open up the world of environmental science and show how human behavior can dramatically alter ecosystems.

  9. Evaluation of antimicrobial resistance of bovine bacteria to antibiotics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antimicrobial resistance (AMR) is one of the most formidable threats to human medicine today. Therefore, the research objective is to evaluate the susceptibility of Staphylococcus species isolated from beef cows to 12 antibiotics commonly used in treating human and animal infections. This research w...

  10. Supercomputer Simulations Help Develop New Approach to Fight Antibiotic Resistance

    ScienceCinema

    Zgurskaya, Helen; Smith, Jeremy

    2016-11-23

    ORNL leveraged powerful supercomputing to support research led by University of Oklahoma scientists to identify chemicals that seek out and disrupt bacterial proteins called efflux pumps, known to be a major cause of antibiotic resistance. By running simulations on Titan, the team selected molecules most likely to target and potentially disable the assembly of efflux pumps found in E. coli bacteria cells.

  11. Antibiotic Resistance in Urinary Tract Infections in College Students

    ERIC Educational Resources Information Center

    Olson, Ronald P.; Haith, Karen

    2012-01-01

    Objective: To determine resistance to antibiotics of "Escherichia coli" in uncomplicated urinary tract infections (uUTIs) in female college students. Participants: Symptomatic patients presenting to a student health service from September 2008 to December 2009. Methods: Clean catch midstream urine samples were tested for urinalysis (UA) and…

  12. Supercomputer Simulations Help Develop New Approach to Fight Antibiotic Resistance

    SciTech Connect

    Zgurskaya, Helen; Smith, Jeremy

    2016-11-17

    ORNL leveraged powerful supercomputing to support research led by University of Oklahoma scientists to identify chemicals that seek out and disrupt bacterial proteins called efflux pumps, known to be a major cause of antibiotic resistance. By running simulations on Titan, the team selected molecules most likely to target and potentially disable the assembly of efflux pumps found in E. coli bacteria cells.

  13. Presence of antibiotic resistance genes in a sewage treatment plant in Thibodaux, Louisiana, USA.

    PubMed

    Naquin, Anthony; Shrestha, Arsen; Sherpa, Mingma; Nathaniel, Rajkumar; Boopathy, Raj

    2015-01-01

    Increasing uses and disposals of antibiotics to the environment have increased emergence of various antibiotic resistance. One of the sources for the spread of antibiotic resistance is wastewater treatment plant, where bacteria and antibiotics can come in contact and can acquire antibiotics resistance. There are very few studies on this subject from a small town sewage treatment plant. Therefore, this study was conducted using raw sewage as well as treated sewage from a sewage treatment plant in Thibodaux in rural southeast Louisiana in USA. Samples were collected monthly from the Thibodaux sewage treatment plant and the presence of antibiotic resistance genes was monitored. The study showed the presence of antibiotic resistance genes in both raw and treated sewage in every month of the study period. The genetic transformation assay showed the successful transformation of methicillin resistant gene, mecA to an antibiotic sensitive Staphylococcus aureus, which became antibiotic resistant within 24h.

  14. Monitoring roadside ditches for antibiotic resistant E. coli in forest and agricultural landscapes

    NASA Astrophysics Data System (ADS)

    Storrer, S.; Archibald, J. A.

    2009-12-01

    There is growing concern over the threat of antibiotic resistant bacteria and how they travel through natural environments. This study was developed to: (1) measure the quantities of antibiotic resistant Escherichia coli present in stormwater collected from roadside ditches, (2) examine the spatial and temporal distribution of antibiotic resistance and (3) explore the difference in antibiotic resistance between different land uses. Autosamplers were used to collect composite samples of stormwater flowing in roadside ditches located near manure fertilized fields or forested areas. Samples were filtered using standard membrane filtration methods and grown with and without antibiotics on EC medium containing MUG. Three antibiotics commonly used to treat infection in humans and dairy cows were used to measure antibiotic resistance: penicillin, ampicillin and tetracycline. Though antibiotic resistance was found at forested and farm sites, preliminary data suggest higher counts of antibiotic resistant E. coli near agricultural areas.

  15. [Resistance to antibiotics in Pseudomonas aeruginosa in Colombian hospitals].

    PubMed

    Villa, Lina M; Cortés, Jorge A; Leal, Aura L; Meneses, Andrés; Meléndez, Martha P

    2013-12-01

    Pseudomonas aeruginosa infections cause high morbidity and mortality. We performed a descriptive analysis of the rates of antibiotic resistance in isolates of P. aeruginosa in 33 hospitals enrolled in a surveillance network in Colombia. The study was conducted between January 2005 and December 2009 .9905 isolates of P. aeruginosa were identified, (4.9% of all strains). In intensive care units (ICU) P. aeruginosa showed an overall resistance to aztreonam, cefepime , ceftazidime, imipenem, meropenem , and piperacillin / tazobactam of 31.8% , 23.9% , 24.8%, 22.5%, 20.3% and 22.3%, respectively. Resistance rates increased for piperacillin/tazobactam, cefepime, and imipenem; remained unchanged for meropenem; and decreased for aminoglycosides, quinolones and ceftazidime. Resistance to one, two and three or more families of antibiotics was found in 17%, 12.5%, and 32.1%, respectively. In samples collected from the wards, the resistance rate was lower but usually over 10%. Antibiotic resistance in P. aeruginosa isolates in hospitalized patients and particularly in those admitted to ICUs in Colombia is high.

  16. Transduction of resistance to some macrolide antibiotics in Staphylococcus aureus.

    PubMed

    PATTEE, P A; BALDWIN, J N

    1962-11-01

    Pattee, P. A. (Iowa State University, Ames) and J. N. Baldwin. Transduction of resistance to some macrolide antibiotics in Staphylococcus aureus. J. Bacteriol. 84:1049-1055. 1962.-By use of phage 80 of the International Typing Series, propagated on appropriate strains of Staphylococcus aureus, two related markers controlling resistance to certain macrolide antibiotics (erythromycin, oleandomycin, spiramycin, and carbomycin) were transduced among a variety of strains of S. aureus. Unlike the markers controlling penicillinase production and resistance to chlortetracycline and novobiocin, the determinants of resistance to the macrolide antibiotics were transduced at normal frequencies (at least 300 transductants per 10(9) phage) only to certain of the recipient strains. One of the markers studied appears to control an inducible enzyme system which is specifically induced by sub-inhibitory concentrations of erythromycin and which controls resistance to erythromycin, oleandomycin, spiramycin, and carbomycin. The other marker examined confers resistance to erythromycin, oleandomycin, spiramycin, and carbomycin, and shows no evidence of being dependent upon an inducible mechanism.

  17. Infections and antibiotic resistance in nursing homes.

    PubMed Central

    Nicolle, L E; Strausbaugh, L J; Garibaldi, R A

    1996-01-01

    Infections occur frequently in nursing home residents. The most common infections are pneumonia, urinary tract infection, and skin and soft tissue infection. Aging-associated physiologic and pathologic changes, functional disability, institutionalization, and invasive devices all contribute to the high occurrence of infection. Antimicrobial agent use in nursing homes is intense and usually empiric. All of these factors contribute to the increasing frequency of antimicrobial agent-resistant organisms in nursing homes. Programs that will limit the emergence and impact of antimicrobial resistance and infections in nursing homes need to be developed. PMID:8665472

  18. Which antibiotic for resistant Gram-positives, and why?

    PubMed

    Bradley, John S

    2014-01-01

    Increasing resistance in Gram-positive pathogens, particularly Staphylococcus aureus, and enterococcus, has become a major clinical problem, particularly in the hospital environment, causing significant morbidity and mortality in both healthy hosts and in those with underlying comorbidities. Increased resistance drives the use of empiric therapy with less well-studied and potentially more toxic agents. Resistance mechanisms for currently recommended agents are discussed, with options for therapy of resistant pathogens. For any new agent used, resistance is likely to develop, which underscores the concept that both antibiotics and antimicrobial resistance are ancient, and only by prudent use of antimicrobial agents and effective infection control measures when resistance arises, will effective agents be available to treat Gram-positive pathogens in the future.

  19. CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database

    PubMed Central

    Jia, Baofeng; Raphenya, Amogelang R.; Alcock, Brian; Waglechner, Nicholas; Guo, Peiyao; Tsang, Kara K.; Lago, Briony A.; Dave, Biren M.; Pereira, Sheldon; Sharma, Arjun N.; Doshi, Sachin; Courtot, Mélanie; Lo, Raymond; Williams, Laura E.; Frye, Jonathan G.; Elsayegh, Tariq; Sardar, Daim; Westman, Erin L.; Pawlowski, Andrew C.; Johnson, Timothy A.; Brinkman, Fiona S.L.; Wright, Gerard D.; McArthur, Andrew G.

    2017-01-01

    The Comprehensive Antibiotic Resistance Database (CARD; http://arpcard.mcmaster.ca) is a manually curated resource containing high quality reference data on the molecular basis of antimicrobial resistance (AMR), with an emphasis on the genes, proteins and mutations involved in AMR. CARD is ontologically structured, model centric, and spans the breadth of AMR drug classes and resistance mechanisms, including intrinsic, mutation-driven and acquired resistance. It is built upon the Antibiotic Resistance Ontology (ARO), a custom built, interconnected and hierarchical controlled vocabulary allowing advanced data sharing and organization. Its design allows the development of novel genome analysis tools, such as the Resistance Gene Identifier (RGI) for resistome prediction from raw genome sequence. Recent improvements include extensive curation of additional reference sequences and mutations, development of a unique Model Ontology and accompanying AMR detection models to power sequence analysis, new visualization tools, and expansion of the RGI for detection of emergent AMR threats. CARD curation is updated monthly based on an interplay of manual literature curation, computational text mining, and genome analysis. PMID:27789705

  20. CARD 2017: expansion and model-centric curation of the comprehensive antibiotic resistance database.

    PubMed

    Jia, Baofeng; Raphenya, Amogelang R; Alcock, Brian; Waglechner, Nicholas; Guo, Peiyao; Tsang, Kara K; Lago, Briony A; Dave, Biren M; Pereira, Sheldon; Sharma, Arjun N; Doshi, Sachin; Courtot, Mélanie; Lo, Raymond; Williams, Laura E; Frye, Jonathan G; Elsayegh, Tariq; Sardar, Daim; Westman, Erin L; Pawlowski, Andrew C; Johnson, Timothy A; Brinkman, Fiona S L; Wright, Gerard D; McArthur, Andrew G

    2017-01-04

    The Comprehensive Antibiotic Resistance Database (CARD; http://arpcard.mcmaster.ca) is a manually curated resource containing high quality reference data on the molecular basis of antimicrobial resistance (AMR), with an emphasis on the genes, proteins and mutations involved in AMR. CARD is ontologically structured, model centric, and spans the breadth of AMR drug classes and resistance mechanisms, including intrinsic, mutation-driven and acquired resistance. It is built upon the Antibiotic Resistance Ontology (ARO), a custom built, interconnected and hierarchical controlled vocabulary allowing advanced data sharing and organization. Its design allows the development of novel genome analysis tools, such as the Resistance Gene Identifier (RGI) for resistome prediction from raw genome sequence. Recent improvements include extensive curation of additional reference sequences and mutations, development of a unique Model Ontology and accompanying AMR detection models to power sequence analysis, new visualization tools, and expansion of the RGI for detection of emergent AMR threats. CARD curation is updated monthly based on an interplay of manual literature curation, computational text mining, and genome analysis.

  1. Antibiotics, Antibiotic Resistance Genes, and Bacterial Community Composition in Fresh Water Aquaculture Environment in China.

    PubMed

    Xiong, Wenguang; Sun, Yongxue; Zhang, Tong; Ding, Xueyao; Li, Yafei; Wang, Mianzhi; Zeng, Zhenling

    2015-08-01

    Environmental antibiotic resistance has drawn increasing attention due to its great threat to human health. In this study, we investigated concentrations of antibiotics (tetracyclines, sulfonamides and (fluoro)quinolones) and abundances of antibiotic resistance genes (ARGs), including tetracycline resistance genes, sulfonamide resistance genes, and plasmid-mediated quinolone resistance genes, and analyzed bacterial community composition in aquaculture environment in Guangdong, China. The concentrations of sulfametoxydiazine, sulfamethazine, sulfamethoxazole, oxytetracycline, chlorotetracycline, doxycycline, ciprofloxacin, norfloxacin, and enrofloxacin were as high as 446 μg kg(-1) and 98.6 ng L(-1) in sediment and water samples, respectively. The relative abundances (ARG copies/16S ribosomal RNA (rRNA) gene copies) of ARGs (sul1, sul2, sul3, tetM, tetO, tetW, tetS, tetQ, tetX, tetB/P, qepA, oqxA, oqxB, aac(6')-Ib, and qnrS) were as high as 2.8 × 10(-2). The dominant phyla were Proteobacteria, Bacteroidetes, and Firmicutes in sediment samples and Proteobacteria, Actinobacteria and Bacteroidetes in water samples. The genera associated with pathogens were also observed, such as Acinetobacter, Arcobacter, and Clostridium. This study comprehensively investigated antibiotics, ARGs, and bacterial community composition in aquaculture environment in China. The results indicated that fish ponds are reservoirs of ARGs and the presence of potential resistant and pathogen-associated taxonomic groups in fish ponds might imply the potential risk to human health.

  2. Intrinsic Resistance of Burkholderia cepacia Complex to Benzalkonium Chloride.

    PubMed

    Ahn, Youngbeom; Kim, Jeong Myeong; Kweon, Ohgew; Kim, Seong-Jae; Jones, Richard C; Woodling, Kellie; Gamboa da Costa, Gonçalo; LiPuma, John J; Hussong, David; Marasa, Bernard S; Cerniglia, Carl E

    2016-11-22

    Pharmaceutical products that are contaminated with Burkholderia cepacia complex (BCC) bacteria may pose serious consequences to vulnerable patients. Benzyldimethylalkylammonium chloride (BZK) cationic surfactants are extensively used in medical applications and have been implicated in the coselection of antimicrobial resistance. The ability of BCC to degrade BZK, tetradecyldimethylbenzylammonium chloride (C14BDMA-Cl), dodecyldimethylbenzylammonium chloride (C12BDMA-Cl), decyldimethylbenzylammonium chloride (C10BDMA-Cl), hexyldimethylbenzylammonium chloride, and benzyltrimethylammonium chloride was determined by incubation in 1/10-diluted tryptic soy broth (TSB) to determine if BCC bacteria have the ability to survive and inactivate these disinfectants. With BZK, C14BDMA-Cl, and C12BDMA-Cl, inhibition of the growth of 20 BCC strains was observed in disinfectant solutions that ranged from 64 to 256 µg/ml. The efflux pump inhibitor carbonyl cyanide m-chlorophenylhydrazone increased the sensitivity of bacteria to 64 µg/ml BZK. The 20 BCC strains grew well in 1/10-diluted TSB medium with BZK, C12BDMA-Cl, and C10BDMA-Cl; they absorbed and degraded the compounds in 7 days. Formation of benzyldimethylamine and benzylmethylamine as the initial metabolites suggested that the cleavage of the C alkyl-N bond occurred as the first step of BZK degradation by BCC bacteria. Proteomic data confirmed the observed efflux activity and metabolic inactivation via biodegradation in terms of BZK resistance of BCC bacteria, which suggests that the two main resistance mechanisms are intrinsic and widespread.

  3. The abundance of antibiotic resistance genes in human guts has correlation to the consumption of antibiotics in animal.

    PubMed

    Hu, Yongfei; Yang, Xi; Lu, Na; Zhu, Baoli

    2014-01-01

    Increasing evidence has accumulated to support that the human gut is a reservoir for antibiotic resistance genes. We previously identified more than 1000 genes displaying high similarity with known antibiotic resistance genes in the human gut gene set generated from the Chinese, Danish, and Spanish populations. Here, first, we add our new understanding of antibiotic resistance genes in the US and the Japanese populations; next, we describe the structure of a vancomycin-resistant operon in a Danish sample; and finally, we provide discussions on the correlation of the abundance of resistance genes in human gut with the antibiotic consumption in human medicine and in animal husbandry. These results, combined with those we published previously, provide comprehensive insights into the antibiotic resistance genes in the human gut microbiota at a population level.

  4. How should we be determining background and baseline antibiotic resistance levels in agroecosystem research?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although historically antibiotic resistance has occurred naturally in environmental bacteria, many questions remain regarding the specifics of how humans and animals contribute to the development and spread of antibiotic resistance in agroecosystems. Additional research is necessary to completely u...

  5. Chlorine inactivation of non-resistant and antibiotic resistant strains of Salmonella Typhimurium isolated from chicken carcasses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A study was conducted to test the hypothesis that strains of Salmonella Typhimurium that are resistant to antibiotics are more resistant to chlorine than strains of S. Typhimurium that are not resistant to antibiotics. To test this hypothesis, strains (n = 16) of S. Typhimurium with four antibiotic...

  6. ABC-F Proteins Mediate Antibiotic Resistance through Ribosomal Protection

    PubMed Central

    Sharkey, Liam K. R.; Edwards, Thomas A.

    2016-01-01

    ABSTRACT Members of the ABC-F subfamily of ATP-binding cassette proteins mediate resistance to a broad array of clinically important antibiotic classes that target the ribosome of Gram-positive pathogens. The mechanism by which these proteins act has been a subject of long-standing controversy, with two competing hypotheses each having gained considerable support: antibiotic efflux versus ribosomal protection. Here, we report on studies employing a combination of bacteriological and biochemical techniques to unravel the mechanism of resistance of these proteins, and provide several lines of evidence that together offer clear support to the ribosomal protection hypothesis. Of particular note, we show that addition of purified ABC-F proteins to an in vitro translation assay prompts dose-dependent rescue of translation, and demonstrate that such proteins are capable of displacing antibiotic from the ribosome in vitro. To our knowledge, these experiments constitute the first direct evidence that ABC-F proteins mediate antibiotic resistance through ribosomal protection. PMID:27006457

  7. Antibiotic resistance-the need for global solutions.

    PubMed

    Laxminarayan, Ramanan; Duse, Adriano; Wattal, Chand; Zaidi, Anita K M; Wertheim, Heiman F L; Sumpradit, Nithima; Vlieghe, Erika; Hara, Gabriel Levy; Gould, Ian M; Goossens, Herman; Greko, Christina; So, Anthony D; Bigdeli, Maryam; Tomson, Göran; Woodhouse, Will; Ombaka, Eva; Peralta, Arturo Quizhpe; Qamar, Farah Naz; Mir, Fatima; Kariuki, Sam; Bhutta, Zulfiqar A; Coates, Anthony; Bergstrom, Richard; Wright, Gerard D; Brown, Eric D; Cars, Otto

    2013-12-01

    The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.

  8. Antibiotic resistance in prevalent bacterial and protozoan sexually transmitted infections

    PubMed Central

    Krupp, Karl; Madhivanan, Purnima

    2015-01-01

    The emergence of multi-drug resistant sexually transmitted infections (STIs) is causing a treatment crisis across the globe. While cephalosporin-resistant gonorrhea is one of the most pressing issues, extensively antibiotic resistant Chlamydia trachomatis and Mycoplasma hominis are also becoming commonplace. Experts have suggested that the failure of current treatment regimens are “largely inevitable” and have called for entirely new classes of antimicrobial agents. With the exception of several new classes of drugs primarily targeting nosocomial infections, progress has been slow. While pharmaceutical companies continue to introduce new drugs, they are based on decade-old discoveries. While there is disagreement about what constitutes new classes of antibiotics, many experts suggest that the last truly new family of antimicrobials was discovered in 1987. This review summarizes the existing literature on antibiotic resistance in common bacterial and protozoal STIs. It also briefly discusses several of the most promising alternatives to current therapies, and further examines how advances in drug delivery, formulation, concentration, and timing are improving the efficacy of existing treatments. Finally, the paper discusses the current state of pharmaceutical development for multidrug-resistant STI. PMID:26392647

  9. Antibiotic treatment and resistance in chronic wounds of vascular origin

    PubMed Central

    TZANEVA, VALENTINA; MLADENOVA, IRENA; TODOROVA, GALINA; PETKOV, DIMITAR

    2016-01-01

    Background and aim The problem of antibiotic resistance is worldwide and affects many types of pathogens. This phenomenon has been growing for decades and nowadays we are faced with a wide range of worrisome pathogens that are becoming resistant and many pathogens that may soon be untreatable. The aim of this study was to determine the resistance and antibiotic treatment in chronic wounds of vascular origin. Methods We performed a cross sectional study on a sample of patients with chronic vascular wounds, hospitalized between October 2014 and August 2015, in the Clinic of Vascular Surgery in Trakia Hospital Stara Zagora. The statistical analysis of data was descriptive, considering the p value of ≤0.05, the threshold of statistical significance. Results In the group of 110 patients, the significantly most frequent chronic wound (p<0.001) was peripheral arteriopathy (47.3%, CI95%: 38.19–56.54). Among 159 strains, 30% of patients having multiple etiology, the species most frequently isolated were Staphylococcus aureus, E.coli, Enterococcus faecalis, Pseudomonas aeruginosa and Proteus mirabilis with a significant predominance (p<0.05) of the Gram negative (55.1%). The spectrum of strains resistance included the Beta-lactams (36.4%, p<0.001), Macrolides (20%), Tetracyclines (9.1%), Aminoglycosides (8.2%) and Fluoroquinolones (4.5%). Conclusions Gram negative microorganisms were the main isolates in patients with vascular chronic wound. Significantly predominant was the resistance to the beta-lactam antibiotics. PMID:27547055

  10. New Technologies for Rapid Bacterial Identification and Antibiotic Resistance Profiling.

    PubMed

    Kelley, Shana O

    2017-04-01

    Conventional approaches to bacterial identification and drug susceptibility testing typically rely on culture-based approaches that take 2 to 7 days to return results. The long turnaround times contribute to the spread of infectious disease, negative patient outcomes, and the misuse of antibiotics that can contribute to antibiotic resistance. To provide new solutions enabling faster bacterial analysis, a variety of approaches are under development that leverage single-cell analysis, microfluidic concentration and detection strategies, and ultrasensitive readout mechanisms. This review discusses recent advances in this area and the potential of new technologies to enable more effective management of infectious disease.

  11. Stochastic expression of a multiple antibiotic resistance activator confers transient resistance in single cells.

    PubMed

    El Meouche, Imane; Siu, Yik; Dunlop, Mary J

    2016-01-13

    Transient resistance can allow microorganisms to temporarily survive lethal concentrations of antibiotics. This can be accomplished through stochastic mechanisms, where individual cells within a population display diverse phenotypes to hedge against the appearance of an antibiotic. To date, research on transient stochastic resistance has focused primarily on mechanisms where a subpopulation of cells enters a dormant, drug-tolerant state. However, a fundamental question is whether stochastic gene expression can also generate variable resistance levels among growing cells in a population. We hypothesized that stochastic expression of antibiotic-inducible resistance mechanisms might play such a role. To investigate this, we focused on a prototypical example of such a system: the multiple antibiotic resistance activator MarA. Previous studies have shown that induction of MarA can lead to a multidrug resistant phenotype at the population level. We asked whether MarA expression also has a stochastic component, even when uninduced. Time lapse microscopy showed that isogenic cells express heterogeneous, dynamic levels of MarA, which were correlated with transient antibiotic survival. This finding has important clinical implications, as stochastic expression of resistance genes may be widespread, allowing populations to hedge against the sudden appearance of an antibiotic.

  12. Why Finish Your Antibiotics? A Novel, Hands-On, Classroom Approach for Teaching the Dynamics of Antibiotic Resistance

    ERIC Educational Resources Information Center

    Wassmer, Gary T.; Kipe-Nolt, Judith A.; Chayko, Catherine A.

    2006-01-01

    We present an effective, engaging, and fun method for teaching how the use or misuse of antibiotics can select for resistant strains of bacteria. This method uses candy as a substitute for strains of bacteria varying in resistance to a given antibiotic. Results and discussion are presented in the context of this emerging healthcare crisis.

  13. Use of commercial organic fertilizer increases the abundance of antibiotic resistance genes and antibiotics in soil.

    PubMed

    Zhou, Xue; Qiao, Min; Wang, Feng-Hua; Zhu, Yong-Guan

    2017-01-01

    The application of manure-based commercial organic fertilizers (COFs) is becoming increasingly extensive because of the expanding market for organic food. The present study examined the effects of repeated applications of chicken or swine manure-based COFs on the fate of antibiotics and antibiotic resistance genes (ARGs) in soil by conducting a soil microcosm experiment. Application of COFs significantly increased antibiotics residues, as well as the relative abundance of ARGs and the integrase gene of class 1 integrons (intΙ1) in soil. Two months after each application, antibiotics and ARGs dissipated in amended soils, but they still remained at an elevated level, compared with the control. And, the accumulation of antibiotics was found due to repeated COF applications. However, the relative abundance of ARGs in most COF-amended soils did not differ significantly between the first application and the repeated application. The results imply that 2 months are not sufficient for ARGs to approach background levels, and that animal manure must be treated more effectively prior to using it in agriculture ecosystems.

  14. What about antibiotic resistance in Neisseria lactamica?

    PubMed

    Arreaza, L; Salcedo, C; Alcalá, B; Vázquez, J A

    2002-03-01

    The in vitro activity of penicillin, ampicillin, cefotaxime, ceftriaxone, rifampicin and ciprofloxacin against 286 Neisseria lactamica isolates was determined by agar dilution and the category of susceptibility was analysed in accordance with the criteria used for Neisseria meningitidis. All isolates were considered to have intermediate susceptibility to penicillin. A total of 1.7% of the isolates were resistant to ampicillin but all were susceptible to cefotaxime and ceftriaxone. Rifampicin MICs ranged between 0.12 and 2 mg/L. Six isolates (2.1%) showed decreased susceptibility to ciprofloxacin.

  15. Antibiotic resistance of Moroccan strains of Salmonella enteritidis isolated between 1996 and 1997.

    PubMed

    Rouahi, N; Zouhdi, M; Zidouh, A; Elyachioui, M; Mahjour, J

    2000-01-01

    Antimicrobial resistance is a worldwide problem. The antibiotic resistance of Moroccan strains of Salmonella enteritidis was investigated from 1996 to 1997. A total of 51 strains were collected within this period, 31 derived from human sources and 20 from food. Of the 31 human strains, 10 were resistant to antibiotics; 4 were resistant to two or more antibiotics. Of the 20 food strains, 11 were resistant to antibiotics; 6 were resistant to two or more antibiotics. The results are similar to those obtained from strains isolated from other Mediterranean countries.

  16. Distribution and quantification of antibiotic resistance genes and bacteria across agricultural and non-agricultural metagenomes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There is concern that antibiotic resistance can potentially be transferred from animals to humans through the food chain. The relationship between specific antibiotic resistant bacteria and the genes they carry remains to be described and few details are known about how antibiotic resistance genes i...

  17. Genotypic Detection of Antibiotic Resistance in "Escherichia Coli.": A Classroom Exercise

    ERIC Educational Resources Information Center

    Longtin, Sarah; Guilfoile, Patrick; Asper, Andrea

    2004-01-01

    Bacterial antibiotic resistance remains a problem of clinical importance. Current microbiological methods for determining antibiotic resistance are based on culturing bacteria, and may require up to 48 hours to complete. Molecular methods are increasingly being developed to speed the identification of antibiotic resistance and to determine its…

  18. Defining antibiotic resistance-towards international harmonization

    PubMed Central

    2014-01-01

    Antimicrobial susceptibility testing with phenotypic methods requires breakpoints, i.e. a minimum inhibitory concentration (MIC) categorizing micro-organisms into susceptible, intermediately susceptible, and resistant for the relevant antimicrobial agent. Determinations of breakpoints require tools such as the understanding of dosing, MIC distributions of organisms without resistance mechanisms, pharmacokinetics, pharmacodynamics, and of clinical outcome in defined clinical situations. Several European countries (France, Germany, Norway, Sweden, the Netherlands, and UK), have national breakpoint committees, often with 20–30 years of experience and tradition. These committees now co-operate under the umbrella of the European Committee on Antimicrobial Susceptibility Testing (EUCAST), organized by The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the European Centre for Disease Prevention and Control (ECDC). Together with the European Medicines Agency (EMA), EUCAST determines breakpoints for existing and new antibacterial and antifungal agents. Moreover, EUCAST has developed a disk diffusion antimicrobial susceptibility testing method which is now, together with the new European breakpoints, being implemented in many countries both inside and outside Europe. PMID:24836050

  19. Detection of antibiotic resistant bacteria inhabiting the sand of non-recreational marine beach.

    PubMed

    Mudryk, Zbigniew; Perliński, Piotr; Skórczewski, Piotr

    2010-02-01

    The present study examined the antibiotic resistance of heterotrophic bacteria, which were isolated from the sand of the beach located in the National Park of the southern Baltic Sea coast. The bacteria demonstrated low levels of antibiotic resistance. These microorganisms were the most resistant to cefaclor and clindamycin and the most sensitive to clarithromycin, doxycycline, gentamycin and oxytetracycline. The majority of bacteria inhabiting the sand of the studied beach were resistant to only one antibiotic out of 18 tested antibiotics in this study. The bacteria inhabiting the middle part of the beach and the dune were more antibiotic resistant than bacteria isolated from the seawater and the shoreline-seawater contact zone. Generally, there was no significant difference in antibiotic resistance between bacteria isolated from the surface and the subsurface sand layers. The bacterial antibiotic resistance level depends on the chemical structure of antibiotics.

  20. Insights into an evolutionary strategy leading to antibiotic resistance

    NASA Astrophysics Data System (ADS)

    Hou, Chun-Feng D.; Liu, Jian-Wei; Collyer, Charles; Mitić, Nataša; Pedroso, Marcelo Monteiro; Schenk, Gerhard; Ollis, David L.

    2017-01-01

    Metallo-β-lactamases (MBLs) with activity towards a broad-spectrum of β-lactam antibiotics have become a major threat to public health, not least due to their ability to rapidly adapt their substrate preference. In this study, the capability of the MBL AIM-1 to evade antibiotic pressure by introducing specific mutations was probed by two alternative methods, i.e. site-saturation mutagenesis (SSM) of active site residues and in vitro evolution. Both approaches demonstrated that a single mutation in AIM-1 can greatly enhance a pathogen’s resistance towards broad spectrum antibiotics without significantly compromising the catalytic efficiency of the enzyme. Importantly, the evolution experiments demonstrated that relevant amino acids are not necessarily in close proximity to the catalytic centre of the enzyme. This observation is a powerful demonstration that MBLs have a diverse array of possibilities to adapt to new selection pressures, avenues that cannot easily be predicted from a crystal structure alone.

  1. Insights into an evolutionary strategy leading to antibiotic resistance

    PubMed Central

    Hou, Chun-Feng D.; Liu, Jian-wei; Collyer, Charles; Mitić, Nataša; Pedroso, Marcelo Monteiro; Schenk, Gerhard; Ollis, David L.

    2017-01-01

    Metallo-β-lactamases (MBLs) with activity towards a broad-spectrum of β-lactam antibiotics have become a major threat to public health, not least due to their ability to rapidly adapt their substrate preference. In this study, the capability of the MBL AIM-1 to evade antibiotic pressure by introducing specific mutations was probed by two alternative methods, i.e. site-saturation mutagenesis (SSM) of active site residues and in vitro evolution. Both approaches demonstrated that a single mutation in AIM-1 can greatly enhance a pathogen’s resistance towards broad spectrum antibiotics without significantly compromising the catalytic efficiency of the enzyme. Importantly, the evolution experiments demonstrated that relevant amino acids are not necessarily in close proximity to the catalytic centre of the enzyme. This observation is a powerful demonstration that MBLs have a diverse array of possibilities to adapt to new selection pressures, avenues that cannot easily be predicted from a crystal structure alone. PMID:28074907

  2. Natural solution to antibiotic resistance: bacteriophages 'The Living Drugs'.

    PubMed

    Jassim, Sabah A A; Limoges, Richard G

    2014-08-01

    Antibiotics have been a panacea in animal husbandry as well as in human therapy for decades. The huge amount of antibiotics used to induce the growth and protect the health of farm animals has lead to the evolution of bacteria that are resistant to the drug's effects. Today, many researchers are working with bacteriophages (phages) as an alternative to antibiotics in the control of pathogens for human therapy as well as prevention, biocontrol, and therapy in animal agriculture. Phage therapy and biocontrol have yet to fulfill their promise or potential, largely due to several key obstacles to their performance. Several suggestions are shared in order to point a direction for overcoming common obstacles in applied phage technology. The key to successful use of phages in modern scientific, farm, food processing and clinical applications is to understand the common obstacles as well as best practices and to develop answers that work in harmony with nature.

  3. The Structure of Fitness Landscapes in Antibiotic-Resistant Bacteria

    NASA Astrophysics Data System (ADS)

    Deris, Barrett; Kim, Minsu; Zhang, Zhongge; Okano, Hiroyuki; Hermsen, Rutger; Gore, Jeff; Hwa, Terence

    2014-03-01

    To predict the emergence of antibiotic resistance, quantitative relations must be established between the fitness of drug-resistant organisms and the molecular mechanisms conferring resistance. We have investigated E. coli strains expressing resistance to translation-inhibiting antibiotics. We show that resistance expression and drug inhibition are linked in a positive feedback loop arising from an innate, global effect of drug-inhibited growth on gene expression. This feedback leads generically to plateau-shaped fitness landscapes and concomitantly, for strains expressing at least moderate degrees of drug resistance, gives rise to an abrupt drop in growth rates of cultures at threshold drug concentrations. A simple quantitative model of bacterial growth based on this innate feedback accurately predicts experimental observations without ad hoc parameter fitting. We describe how drug-inhibited growth rate and the threshold drug concentration (the minimum inhibitory concentration, or MIC) depend on the few biochemical parameters that characterize the molecular details of growth inhibition and drug resistance (e.g., the drug-target dissociation constant). And finally, we discuss how these parameters can shape fitness landscapes to determine evolutionary dynamics and evolvability.

  4. Where antibiotic resistance mutations meet quorum-sensing

    PubMed Central

    Krašovec, Rok; Belavkin, Roman V.; Aston, John A.; Channon, Alastair; Aston, Elizabeth; Rash, Bharat M.; Kadirvel, Manikandan; Forbes, Sarah; Knight, Christopher G.

    2014-01-01

    We do not need to rehearse the grim story of the global rise of antibiotic resistant microbes. But what if it were possible to control the rate with which antibiotic resistance evolves by de novo mutation? It seems that some bacteria may already do exactly that: they modify the rate at which they mutate to antibiotic resistance dependent on their biological environment. In our recent study [Krašovec, et al. Nat. Commun. (2014), 5, 3742] we find that this modification depends on the density of the bacterial population and cell-cell interactions (rather than, for instance, the level of stress). Specifically, the wild-type strains of Escherichia coli we used will, in minimal glucose media, modify their rate of mutation to rifampicin resistance according to the density of wild-type cells. Intriguingly, the higher the density, the lower the mutation rate (Figure 1). Why this novel density-dependent ‘mutation rate plasticity’ (DD-MRP) occurs is a question at several levels. Answers are currently fragmentary, but involve the quorum-sensing gene luxS and its role in the activated methyl cycle.

  5. Optimizing drug exposure to minimize selection of antibiotic resistance.

    PubMed

    Olofsson, Sara K; Cars, Otto

    2007-09-01

    The worldwide increase in antibiotic resistance is a concern for public health. The fact that the choice of dose and treatment duration can affect the selection of antibiotic-resistant mutants is becoming more evident, and an increased number of studies have used pharmacodynamic models to describe the drug exposure and pharmacodynamic breakpoints needed to minimize and predict the development of resistance. However, there remains a lack of sufficient data, and future work is needed to fully characterize these target drug concentrations. More knowledge is also needed of drug pharmacodynamics versus bacteria with different resistance mutations and susceptibility levels. The dosing regimens should exhibit high efficacy not only against susceptible wild-type bacteria but, preferably, also against mutated bacteria that may exist in low numbers in "susceptible" populations. Thus, to prolong the life span of existing and new antibiotics, it is important that dosing regimens be carefully selected on the basis of pharmacokinetic and pharmacodynamic properties that prevent emergence of preexisting and newly formed mutants.

  6. Intrinsic resistance to JAK2 inhibition in myelofibrosis

    PubMed Central

    Kalota, Anna; Jeschke, Grace R.; Carroll, Martin; Hexner, Elizabeth O.

    2013-01-01

    Purpose Recent results have demonstrated that myeloproliferative neoplasms (MPN) are strongly associated with constitutive activation of the JAK2 tyrosine kinase. However, JAK2 inhibitors currently approved or under development for treating myeloproliferative neoplasms do not selectively deplete the malignant clone, and the inhibition of activity of the drug target (JAK2) has not been rigorously evaluated in clinical studies. Therefore in this study we developed an in vitro assay to gain insight into how effectively JAK2 activity is inhibited in patient samples. Experimental Design We treated primary cells from normal donors and patients with MPN with JAK2 inhibitors and measured phosphorylation of downstream targets STAT5 and STAT3 by flow cytometry. Obtained results were next correlated with JAK2 V617F allele burden and plasma cytokines level. Results We observed a dose-dependent decrease in pSTAT5 and pSTAT3 in ex vivo treated granulocytes. However, phosphorylation of STAT3 and STAT5 in cells from patients with myelofibrosis was significantly less inhibited when compared to cells from patients with polycythemia vera, essential thrombocytosis, and normal donors. Sensitivity to inhibition did not correlate with JAK2 V617F clonal burden. Mixing studies using plasma from patients with myelofibrosis did not transfer resistance to sensitive cells. Likewise, no single cytokine measured appeared to account for the observed pattern of resistance. Taken together these observations suggest that there are cell intrinsic mechanisms that define a priori resistance to JAK2 inhibition in myelofibrosis, and the lesion is localized upstream of STAT3 and STAT5. PMID:23386690

  7. Intrinsic Resistance of Burkholderia cepacia Complex to Benzalkonium Chloride

    PubMed Central

    Ahn, Youngbeom; Kim, Jeong Myeong; Kweon, Ohgew; Kim, Seong-Jae; Jones, Richard C.; Woodling, Kellie; Gamboa da Costa, Gonçalo; LiPuma, John J.; Hussong, David; Marasa, Bernard S.

    2016-01-01

    ABSTRACT Pharmaceutical products that are contaminated with Burkholderia cepacia complex (BCC) bacteria may pose serious consequences to vulnerable patients. Benzyldimethylalkylammonium chloride (BZK) cationic surfactants are extensively used in medical applications and have been implicated in the coselection of antimicrobial resistance. The ability of BCC to degrade BZK, tetradecyldimethylbenzylammonium chloride (C14BDMA-Cl), dodecyldimethylbenzylammonium chloride (C12BDMA-Cl), decyldimethylbenzylammonium chloride (C10BDMA-Cl), hexyldimethylbenzylammonium chloride, and benzyltrimethylammonium chloride was determined by incubation in 1/10-diluted tryptic soy broth (TSB) to determine if BCC bacteria have the ability to survive and inactivate these disinfectants. With BZK, C14BDMA-Cl, and C12BDMA-Cl, inhibition of the growth of 20 BCC strains was observed in disinfectant solutions that ranged from 64 to 256 µg/ml. The efflux pump inhibitor carbonyl cyanide m-chlorophenylhydrazone increased the sensitivity of bacteria to 64 µg/ml BZK. The 20 BCC strains grew well in 1/10-diluted TSB medium with BZK, C12BDMA-Cl, and C10BDMA-Cl; they absorbed and degraded the compounds in 7 days. Formation of benzyldimethylamine and benzylmethylamine as the initial metabolites suggested that the cleavage of the C alkyl-N bond occurred as the first step of BZK degradation by BCC bacteria. Proteomic data confirmed the observed efflux activity and metabolic inactivation via biodegradation in terms of BZK resistance of BCC bacteria, which suggests that the two main resistance mechanisms are intrinsic and widespread. PMID:27879334

  8. The problems of antibiotic resistance in cystic fibrosis and solutions.

    PubMed

    López-Causapé, Carla; Rojo-Molinero, Estrella; Macià, María D; Oliver, Antonio

    2015-02-01

    Chronic respiratory infection is the main cause of morbidity and mortality in cystic fibrosis (CF) patients. One of the hallmarks of these infections, led by the opportunistic pathogen Pseudomonas aeruginosa, is their long-term (lifelong) persistence despite intensive antimicrobial therapy. Antimicrobial resistance in CF is indeed a multifactorial problem, which includes physiological changes, represented by the transition from the planktonic to the biofilm mode of growth and the acquisition of multiple (antibiotic resistance) adaptive mutations catalyzed by frequent mutator phenotypes. Emerging multidrug-resistant CF pathogens, transmissible epidemic strains and transferable genetic elements (such as those encoding class B carbapenemases) also significantly contribute to this concerning scenario. Strategies directed to combat biofilm growth, prevent the emergence of mutational resistance, promote the development of novel antimicrobial agents against multidrug-resistant strains and implement strict infection control measures are thus needed.

  9. Impact of dairy manure pre-application treatment on manure composition, soil dynamics of antibiotic resistance genes, and abundance of antibiotic-resistance genes on vegetables at harvest.

    PubMed

    Tien, Yuan-Ching; Li, Bing; Zhang, Tong; Scott, Andrew; Murray, Roger; Sabourin, Lyne; Marti, Romain; Topp, Edward

    2017-03-01

    Manuring ground used for crop production is an important agricultural practice. Should antibiotic-resistant enteric bacteria carried in the manure be transferred to crops that are consumed raw, their consumption by humans or animals will represent a route of exposure to antibiotic resistance genes. Treatment of manures prior to land application is a potential management option to reduce the abundance of antibiotic resistance genes entrained with manure application. In this study, dairy manure that was untreated, anaerobically digested, mechanically dewatered or composted was applied to field plots that were then cropped to lettuce, carrots and radishes. The impact of treatment on manure composition, persistence of antibiotic resistance gene targets in soil following application, and distribution of antibiotic resistance genes and bacteria on vegetables at harvest was determined. Composted manure had the lowest abundance of antibiotic resistance gene targets compared to the other manures. There was no significant difference in the persistence characteristics of antibiotic resistance genes following land application of the various manures. Compared to unmanured soil, antibiotic resistance genes were detected more frequently in soil receiving raw or digested manure, whereas they were not in soil receiving composted manure. The present study suggests that vegetables grown in ground receiving raw or digested manure are at risk of contamination with manure-borne antibiotic resistant bacteria, whereas vegetables grown in ground receiving composted manure are less so.

  10. Rifampin phosphotransferase is an unusual antibiotic resistance kinase

    PubMed Central

    Stogios, Peter J.; Cox, Georgina; Spanogiannopoulos, Peter; Pillon, Monica C.; Waglechner, Nicholas; Skarina, Tatiana; Koteva, Kalinka; Guarné, Alba; Savchenko, Alexei; Wright, Gerard D.

    2016-01-01

    Rifampin (RIF) phosphotransferase (RPH) confers antibiotic resistance by conversion of RIF and ATP, to inactive phospho-RIF, AMP and Pi. Here we present the crystal structure of RPH from Listeria monocytogenes (RPH-Lm), which reveals that the enzyme is comprised of three domains: two substrate-binding domains (ATP-grasp and RIF-binding domains); and a smaller phosphate-carrying His swivel domain. Using solution small-angle X-ray scattering and mutagenesis, we reveal a mechanism where the swivel domain transits between the spatially distinct substrate-binding sites during catalysis. RPHs are previously uncharacterized dikinases that are widespread in environmental and pathogenic bacteria. These enzymes are members of a large unexplored group of bacterial enzymes with substrate affinities that have yet to be fully explored. Such an enzymatically complex mechanism of antibiotic resistance augments the spectrum of strategies used by bacteria to evade antimicrobial compounds. PMID:27103605

  11. Rifampin phosphotransferase is an unusual antibiotic resistance kinase.

    PubMed

    Stogios, Peter J; Cox, Georgina; Spanogiannopoulos, Peter; Pillon, Monica C; Waglechner, Nicholas; Skarina, Tatiana; Koteva, Kalinka; Guarné, Alba; Savchenko, Alexei; Wright, Gerard D

    2016-04-22

    Rifampin (RIF) phosphotransferase (RPH) confers antibiotic resistance by conversion of RIF and ATP, to inactive phospho-RIF, AMP and Pi. Here we present the crystal structure of RPH from Listeria monocytogenes (RPH-Lm), which reveals that the enzyme is comprised of three domains: two substrate-binding domains (ATP-grasp and RIF-binding domains); and a smaller phosphate-carrying His swivel domain. Using solution small-angle X-ray scattering and mutagenesis, we reveal a mechanism where the swivel domain transits between the spatially distinct substrate-binding sites during catalysis. RPHs are previously uncharacterized dikinases that are widespread in environmental and pathogenic bacteria. These enzymes are members of a large unexplored group of bacterial enzymes with substrate affinities that have yet to be fully explored. Such an enzymatically complex mechanism of antibiotic resistance augments the spectrum of strategies used by bacteria to evade antimicrobial compounds.

  12. A Hybrid Drug Limits Resistance by Evading the Action of the Multiple Antibiotic Resistance Pathway

    PubMed Central

    Wang, Kathy K.; Stone, Laura K.; Lieberman, Tami D.; Shavit, Michal; Baasov, Timor; Kishony, Roy

    2016-01-01

    Hybrid drugs are a promising strategy to address the growing problem of drug resistance, but the mechanism by which they modulate the evolution of resistance is poorly understood. Integrating high-throughput resistance measurements and genomic sequencing, we compared Escherichia coli populations evolved in a hybrid antibiotic that links ciprofloxacin and neomycin B with populations evolved in combinations of the component drugs. We find that populations evolved in the hybrid gain less resistance than those evolved in an equimolar mixture of the hybrid’s components, in part because the hybrid evades resistance mediated by the multiple antibiotic resistance (mar) operon. Furthermore, we find that the ciprofloxacin moiety of the hybrid inhibits bacterial growth whereas the neomycin B moiety diminishes the effectiveness of mar activation. More generally, comparing the phenotypic and genotypic paths to resistance across different drug treatments can pinpoint unique properties of new compounds that limit the emergence of resistance. PMID:26538141

  13. A Hybrid Drug Limits Resistance by Evading the Action of the Multiple Antibiotic Resistance Pathway.

    PubMed

    Wang, Kathy K; Stone, Laura K; Lieberman, Tami D; Shavit, Michal; Baasov, Timor; Kishony, Roy

    2016-02-01

    Hybrid drugs are a promising strategy to address the growing problem of drug resistance, but the mechanism by which they modulate the evolution of resistance is poorly understood. Integrating high-throughput resistance measurements and genomic sequencing, we compared Escherichia coli populations evolved in a hybrid antibiotic that links ciprofloxacin and neomycin B with populations evolved in combinations of the component drugs. We find that populations evolved in the hybrid gain less resistance than those evolved in an equimolar mixture of the hybrid's components, in part because the hybrid evades resistance mediated by the multiple antibiotic resistance (mar) operon. Furthermore, we find that the ciprofloxacin moiety of the hybrid inhibits bacterial growth whereas the neomycin B moiety diminishes the effectiveness of mar activation. More generally, comparing the phenotypic and genotypic paths to resistance across different drug treatments can pinpoint unique properties of new compounds that limit the emergence of resistance.

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

    PubMed

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

    2016-12-01

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

  15. Diversity and antibiotic resistance of Aeromonas spp. in drinking and waste water treatment plants.

    PubMed

    Figueira, Vânia; Vaz-Moreira, Ivone; Silva, Márcia; Manaia, Célia M

    2011-11-01

    The taxonomic diversity and antibiotic resistance phenotypes of aeromonads were examined in samples from drinking and waste water treatment plants (surface, ground and disinfected water in a drinking water treatment plant, and raw and treated waste water) and tap water. Bacteria identification and intra-species variation were determined based on the analysis of the 16S rRNA, gyrB and cpn60 gene sequences. Resistance phenotypes were determined using the disc diffusion method. Aeromonas veronii prevailed in raw surface water, Aeromonas hydrophyla in ozonated water, and Aeromonas media and Aeromonas puntacta in waste water. No aeromonads were detected in ground water, after the chlorination tank or in tap water. Resistance to ceftazidime or meropenem was detected in isolates from the drinking water treatment plant and waste water isolates were intrinsically resistant to nalidixic acid. Most of the times, quinolone resistance was associated with the gyrA mutation in serine 83. The gene qnrS, but not the genes qnrA, B, C, D or qepA, was detected in both surface and waste water isolates. The gene aac(6')-ib-cr was detected in different waste water strains isolated in the presence of ciprofloxacin. Both quinolone resistance genes were detected only in the species A. media. This is the first study tracking antimicrobial resistance in aeromonads in drinking, tap and waste water and the importance of these bacteria as vectors of resistance in aquatic environments is discussed.

  16. Economic burden of antibiotic resistance: how much do we really know?

    PubMed

    Gandra, S; Barter, D M; Laxminarayan, R

    2014-10-01

    The declining effectiveness of antibiotics imposes potentially large health and economic burdens on societies. Quantifying the economic outcomes of antibiotic resistance effectively can help policy-makers and healthcare professionals to set priorities, but determining the actual effect of antibiotic resistance on clinical outcomes is a necessary first step. In this article, we review and discuss the contributions and limitations of studies that estimate the disease burden attributable to antibiotic resistance and studies that estimate the economic burden of resistance. We also consider other factors that are important in a comprehensive approach to evaluating the economic burden of antibiotic resistance.

  17. Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium.

    PubMed

    Mdluli, K; Swanson, J; Fischer, E; Lee, R E; Barry, C E

    1998-03-01

    Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very potent against the tuberculous mycobacteria. It is about 100-fold less effective against Mycobacterium avium. This difference has often been attributed to a decreased permeability of the cell wall. We measured the rate of conversion of radiolabelled INH to 4-pyridylmethanol by whole cells and cell-free extracts and estimated the permeability barrier imposed by the cell wall to INH influx in Mycobacterium tuberculosis and M. avium. There was no significant difference in the relative permeability to INH between these two species. However, the total conversion rate in M. tuberculosis was found to be four times greater. Examination of in vitro-generated mutants revealed that the major resistance mechanism for both species is loss of the catalase-peroxidase KatG. Analysis of lipid and protein biosynthetic profiles demonstrated that the molecular target of activated INH was identical for both species. M. avium, however, formed colonies at INH concentrations inhibitory for mycolic acid biosynthesis. These mycolate-deficient M. avium exhibited altered colony morphologies, modified cell wall ultrastructure and were 10-fold more sensitive to treatment with hydrophobic antibiotics, such as rifampin. These findings may significantly impact the design of new therapeutic regimens for the treatment of infections with atypical mycobacteria.

  18. Distribution and Quantification of Antibiotic Resistant Genes and Bacteria across Agricultural and Non-Agricultural Metagenomes

    PubMed Central

    Durso, Lisa M.; Miller, Daniel N.; Wienhold, Brian J.

    2012-01-01

    There is concern that antibiotic resistance can potentially be transferred from animals to humans through the food chain. The relationship between specific antibiotic resistant bacteria and the genes they carry remains to be described. Few details are known about the ecology of antibiotic resistant genes and bacteria in food production systems, or how antibiotic resistance genes in food animals compare to antibiotic resistance genes in other ecosystems. Here we report the distribution of antibiotic resistant genes in publicly available agricultural and non-agricultural metagenomic samples and identify which bacteria are likely to be carrying those genes. Antibiotic resistance, as coded for in the genes used in this study, is a process that was associated with all natural, agricultural, and human-impacted ecosystems examined, with between 0.7 to 4.4% of all classified genes in each habitat coding for resistance to antibiotic and toxic compounds (RATC). Agricultural, human, and coastal-marine metagenomes have characteristic distributions of antibiotic resistance genes, and different bacteria that carry the genes. There is a larger percentage of the total genome associated with antibiotic resistance in gastrointestinal-associated and agricultural metagenomes compared to marine and Antarctic samples. Since antibiotic resistance genes are a natural part of both human-impacted and pristine habitats, presence of these resistance genes in any specific habitat is therefore not sufficient to indicate or determine impact of anthropogenic antibiotic use. We recommend that baseline studies and control samples be taken in order to determine natural background levels of antibiotic resistant bacteria and/or antibiotic resistance genes when investigating the impacts of veterinary use of antibiotics on human health. We raise questions regarding whether the underlying biology of each type of bacteria contributes to the likelihood of transfer via the food chain. PMID:23133629

  19. Exploring the contribution of bacteriophages to antibiotic resistance.

    PubMed

    Lekunberri, Itziar; Subirats, Jèssica; Borrego, Carles M; Balcázar, José Luis

    2017-01-01

    Bacteriophages (phages) are the most abundant and diverse biological entities in our planet. They infect susceptible bacterial hosts into which they either multiply or persist. In the latter case, phages can confer new functions to their hosts as a result of gene transfer, thus contributing to their adaptation (short-term) and evolution (long-term). In this regard, the role of phages on the dissemination of antibiotic resistance genes (ARGs) among bacterial hosts in natural environments has not yet been clearly resolved. Here, we carry out a comprehensive analysis of thirty-three viromes from different habitats to investigate whether phages harbor ARGs. Our results demonstrate that while human-associated viromes do not or rarely carry ARGs, viromes from non-human sources (e.g. pig feces, raw sewage, and freshwater and marine environments) contain a large reservoir of ARGs, thus pointing out that phages could play a part on the spread of antibiotic resistance. Given this, the role of phages should not be underestimated and it should be considered when designing strategies to tackle the global crisis of antibiotic resistance.

  20. Effect of subtherapeutic administration of antibiotics on the prevalence of antibiotic-resistant Escherichia coli bacteria in feedlot cattle.

    PubMed

    Alexander, T W; Yanke, L J; Topp, E; Olson, M E; Read, R R; Morck, D W; McAllister, T A

    2008-07-01

    Antibiotic-resistant Escherichia coli in 300 feedlot steers receiving subtherapeutic levels of antibiotics was investigated through the collection of 3,300 fecal samples over a 314-day period. Antibiotics were selected based on the commonality of use in the industry and included chlortetracycline plus sulfamethazine (TET-SUL), chlortetracycline (TET), virginiamycin, monensin, tylosin, or no antibiotic supplementation (control). Steers were initially fed a barley silage-based diet, followed by transition to a barley grain-based diet. Despite not being administered antibiotics prior to arrival at the feedlot, the prevalences of steers shedding TET- and ampicillin (AMP)-resistant E. coli were >40 and <30%, respectively. Inclusion of TET-SUL in the diet increased the prevalence of steers shedding TET- and AMP-resistant E. coli and the percentage of TET- and AMP-resistant E. coli in the total generic E. coli population. Irrespective of treatment, the prevalence of steers shedding TET-resistant E. coli was higher in animals fed grain-based compared to silage-based diets. All steers shed TET-resistant E. coli at least once during the experiment. A total of 7,184 isolates were analyzed for MIC of antibiotics. Across antibiotic treatments, 1,009 (13.9%), 7 (0.1%), and 3,413 (47.1%) E. coli isolates were resistant to AMP, gentamicin, or TET, respectively. In addition, 131 (1.8%) and 143 (2.0%) isolates exhibited potential resistance to extended-spectrum beta-lactamases, as indicated by either ceftazidime or cefpodoxime resistance. No isolates were resistant to ciprofloxacin. The findings of the present study indicated that subtherapeutic administration of tetracycline in combination with sulfamethazine increased the prevalence of tetracycline- and AMP-resistant E. coli in cattle. However, resistance to antibiotics may be related to additional environmental factors such as diet.

  1. Calcined Eggshell Waste for Mitigating Soil Antibiotic-Resistant Bacteria/Antibiotic Resistance Gene Dissemination and Accumulation in Bell Pepper.

    PubMed

    Ye, Mao; Sun, Mingming; Feng, Yanfang; Li, Xu; Schwab, Arthur P; Wan, Jinzhong; Liu, Manqiang; Tian, Da; Liu, Kuan; Wu, Jun; Jiang, Xin

    2016-07-13

    The combined accumulation of antibiotics, heavy metals, antibiotic-resistant bacteria (ARB)/antibiotic resistance genes (ARGs) in vegetables has become a new threat to human health. This is the first study to investigate the feasibility of calcined eggshells modified by aluminum sulfate as novel agricultural wastes to impede mixed contaminants from transferring to bell pepper (Capsicum annuum L.). In this work, calcined eggshell amendment mitigated mixed pollutant accumulation in bell pepper significantly, enhanced the dissipation of soil tetracycline, sulfadiazine, roxithromycin, and chloramphenicol, decreased the water-soluble fractions of antibiotics, and declined the diversity of ARB/ARGs inside the vegetable. Moreover, quantitative polymerase chain reaction analysis detected that ARG levels in the bell pepper fruits significantly decreased to 10(-10) copies/16S copies, indicating limited risk of ARGs transferring along the food chain. Furthermore, the restoration of soil microbial biological function suggests that calcined eggshell is an environmentally friendly amendment to control the dissemination of soil ARB/ARGs in the soil-vegetable system.

  2. Antibiotic treatments of a methicillin-resistant Staphylococcus pseudintermedius infection in a dog: a case presentation.

    PubMed

    Decristophoris, P; Mauri, F; Albanese, F; Carnelli, A; Vanzetti, T; Zinsstag, J

    2011-09-01

    We report the antibiotic treatments administered to a female dog with mastitis and successive pyoderma. Microbiological investigations allowed the identification of Staphylococcus pseudintermedius after 54 days of various antibiotic treatments. The isolate carried the mecA gene and was resistant to 9 of 15 tested antibiotics. Consistent antibiotic treatment of the infection was possible only after accurate microbiological diagnosis.

  3. The scourge of antibiotic resistance: the important role of the environment.

    PubMed

    Finley, Rita L; Collignon, Peter; Larsson, D G Joakim; McEwen, Scott A; Li, Xian-Zhi; Gaze, William H; Reid-Smith, Richard; Timinouni, Mohammed; Graham, David W; Topp, Edward

    2013-09-01

    Antibiotic resistance and associated genes are ubiquitous and ancient, with most genes that encode resistance in human pathogens having originated in bacteria from the natural environment (eg, β-lactamases and fluoroquinolones resistance genes, such as qnr). The rapid evolution and spread of "new" antibiotic resistance genes has been enhanced by modern human activity and its influence on the environmental resistome. This highlights the importance of including the role of the environmental vectors, such as bacterial genetic diversity within soil and water, in resistance risk management. We need to take more steps to decrease the spread of resistance genes in environmental bacteria into human pathogens, to decrease the spread of resistant bacteria to people and animals via foodstuffs, wastes and water, and to minimize the levels of antibiotics and antibiotic-resistant bacteria introduced into the environment. Reducing this risk must include improved management of waste containing antibiotic residues and antibiotic-resistant microorganisms.

  4. The gut is the epicentre of antibiotic resistance

    PubMed Central

    2012-01-01

    The gut contains very large numbers of bacteria. Changes in the composition of the gut flora, due in particular to antibiotics, can happen silently, leading to the selection of highly resistant bacteria and Candida species. These resistant organisms may remain for months in the gut of the carrier without causing any symptoms or translocate through the gut epithelium, induce healthcare-associated infections, undergo cross-transmission to other individuals, and cause limited outbreaks. Techniques are available to prevent, detect, and treat the carriage of resistant organisms in the gut. However, evidence on these techniques is scant, the only exception being selective digestive decontamination (SDD), which has been extensively studied in neutropenic and ICU patients. After the destruction of resistant colonizing bacteria, which has been successfully obtained in several studies, the gut could be re-colonized with normal faecal flora or probiotics. Studies are warranted to evaluate this concept. PMID:23181506

  5. Epidemiology and antibiotic resistance in a large Italian teaching hospital.

    PubMed

    Esposito, Silvano; Pascale, Renato; Esposito, Isabella; Noviello, Silvana; Russo, Enrico; Simone, Giuseppe De; Vitolo, Matilde; Rega, Maria Rosaria; Massari, Angelo

    2015-06-01

    We focused our attention on susceptibility profile of Acinetobacter spp., Pseudomonas spp., and Klebsiella spp. isolated from biological specimens at the University Hospital of Salerno between June 2011 and October 2012. Acinetobacter, with a prevalence of Acinetobacter baumannii (97%) presented a high range of resistance to the antimicrobials considered, excluding colistin (COL). Klebsiella spp. isolates, with a prevalence of Klebsiella pneumoniae (90%), presented a variable pattern of resistance [from 9·8% for COL to 50% for levofloxacin (LEV)]. Extended-spectrum beta-lactamases production was detected in 15% of isolates. Most Pseudomonas isolates were P. aeruginosa with a high rate of resistance (95% to amoxicillin/clavulanate and trimethoprim/sulfamethoxazole, and <50% to the other antibiotics). Colistin remained the most effective drug tested. This study provided useful information of the local bacterial epidemiology hopefully permitting to establish a more effective empirical therapy, preventing the inappropriate use of antibacterial agents and possibly limiting the diffusion of antibacterial resistance.

  6. Antibiotics as selectors and accelerators of diversity in the mechanisms of resistance: from the resistome to genetic plasticity in the β-lactamases world

    PubMed Central

    Galán, Juan-Carlos; González-Candelas, Fernando; Rolain, Jean-Marc; Cantón, Rafael

    2013-01-01

    Antibiotics and antibiotic resistance determinants, natural molecules closely related to bacterial physiology and consistent with an ancient origin, are not only present in antibiotic-producing bacteria. Throughput sequencing technologies have revealed an unexpected reservoir of antibiotic resistance in the environment. These data suggest that co-evolution between antibiotic and antibiotic resistance genes has occurred since the beginning of time. This evolutionary race has probably been slow because of highly regulated processes and low antibiotic concentrations. Therefore to understand this global problem, a new variable must be introduced, that the antibiotic resistance is a natural event, inherent to life. However, the industrial production of natural and synthetic antibiotics has dramatically accelerated this race, selecting some of the many resistance genes present in nature and contributing to their diversification. One of the best models available to understand the biological impact of selection and diversification are β-lactamases. They constitute the most widespread mechanism of resistance, at least among pathogenic bacteria, with more than 1000 enzymes identified in the literature. In the last years, there has been growing concern about the description, spread, and diversification of β-lactamases with carbapenemase activity and AmpC-type in plasmids. Phylogenies of these enzymes help the understanding of the evolutionary forces driving their selection. Moreover, understanding the adaptive potential of β-lactamases contribute to exploration the evolutionary antagonists trajectories through the design of more efficient synthetic molecules. In this review, we attempt to analyze the antibiotic resistance problem from intrinsic and environmental resistomes to the adaptive potential of resistance genes and the driving forces involved in their diversification, in order to provide a global perspective of the resistance problem. PMID:23404545

  7. Antibiotics as selectors and accelerators of diversity in the mechanisms of resistance: from the resistome to genetic plasticity in the β-lactamases world.

    PubMed

    Galán, Juan-Carlos; González-Candelas, Fernando; Rolain, Jean-Marc; Cantón, Rafael

    2013-01-01

    Antibiotics and antibiotic resistance determinants, natural molecules closely related to bacterial physiology and consistent with an ancient origin, are not only present in antibiotic-producing bacteria. Throughput sequencing technologies have revealed an unexpected reservoir of antibiotic resistance in the environment. These data suggest that co-evolution between antibiotic and antibiotic resistance genes has occurred since the beginning of time. This evolutionary race has probably been slow because of highly regulated processes and low antibiotic concentrations. Therefore to understand this global problem, a new variable must be introduced, that the antibiotic resistance is a natural event, inherent to life. However, the industrial production of natural and synthetic antibiotics has dramatically accelerated this race, selecting some of the many resistance genes present in nature and contributing to their diversification. One of the best models available to understand the biological impact of selection and diversification are β-lactamases. They constitute the most widespread mechanism of resistance, at least among pathogenic bacteria, with more than 1000 enzymes identified in the literature. In the last years, there has been growing concern about the description, spread, and diversification of β-lactamases with carbapenemase activity and AmpC-type in plasmids. Phylogenies of these enzymes help the understanding of the evolutionary forces driving their selection. Moreover, understanding the adaptive potential of β-lactamases contribute to exploration the evolutionary antagonists trajectories through the design of more efficient synthetic molecules. In this review, we attempt to analyze the antibiotic resistance problem from intrinsic and environmental resistomes to the adaptive potential of resistance genes and the driving forces involved in their diversification, in order to provide a global perspective of the resistance problem.

  8. Improved annotation of antibiotic resistance determinants reveals microbial resistomes cluster by ecology.

    PubMed

    Gibson, Molly K; Forsberg, Kevin J; Dantas, Gautam

    2015-01-01

    Antibiotic resistance is a dire clinical problem with important ecological dimensions. While antibiotic resistance in human pathogens continues to rise at alarming rates, the impact of environmental resistance on human health is still unclear. To investigate the relationship between human-associated and environmental resistomes, we analyzed functional metagenomic selections for resistance against 18 clinically relevant antibiotics from soil and human gut microbiota as well as a set of multidrug-resistant cultured soil isolates. These analyses were enabled by Resfams, a new curated database of protein families and associated highly precise and accurate profile hidden Markov models, confirmed for antibiotic resistance function and organized by ontology. We demonstrate that the antibiotic resistance functions that give rise to the resistance profiles observed in environmental and human-associated microbial communities significantly differ between ecologies. Antibiotic resistance functions that most discriminate between ecologies provide resistance to β-lactams and tetracyclines, two of the most widely used classes of antibiotics in the clinic and agriculture. We also analyzed the antibiotic resistance gene composition of over 6000 sequenced microbial genomes, revealing significant enrichment of resistance functions by both ecology and phylogeny. Together, our results indicate that environmental and human-associated microbial communities harbor distinct resistance genes, suggesting that antibiotic resistance functions are largely constrained by ecology.

  9. Assessment of selected antibiotic resistances in ungrazed native Nebraska prairie soils

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Measurements of antibiotic resistance from manure-impacted soils result in conflated data. It is difficult to sort out the features that are a result of human antibiotic use, from the features that are a result of the inherent spatial heterogeneity, complexity and dynamics of antibiotic resistant b...

  10. Ornamental fish as a source of plasmid-mediated quinolone resistance genes and antibiotic resistance plasmids.

    PubMed

    Dobiasova, Hana; Kutilova, Iva; Piackova, Veronika; Vesely, Tomas; Cizek, Alois; Dolejska, Monika

    2014-07-16

    Growing ornamental fish industry is associated with public health concerns including extensive antibiotic use accompanied by increasing antibiotic resistance. The aim of this study was to analyze Aeromonas isolates from imported tropical ornamental fish and coldwater koi carps bred in the Czech Republic to assess the potential risk of ornamental fish as a source of plasmid-mediated quinolone resistance genes (PMQR) and antibiotic resistance plasmids. A collection of Aeromonas spp. with reduced susceptibility to ciprofloxacin (MIC ≥ 0.05 mg/L) was selected for the detection of PMQR genes. Isolates harbouring PMQR genes were further analyzed for the additional antibiotic resistance, integron content, clonality, biofilm production and transferability of PMQR genes by conjugation and transformation. Comparative analysis of plasmids carrying PMQR genes was performed. Fifteen (19%, n=80) isolates from koi carps and 18 (24%, n=76) isolates from imported ornamental fish were positive for qnrS2, aac(6')-Ib-cr or qnrB17 genes. PMQR-positive isolates from imported ornamental fish showed higher MIC levels to quinolones, multiresistance and diverse content of antibiotic resistance genes and integrons compared to the isolates from the carps. Related IncU plasmids harbouring qnrS2 and aac(6')-Ib-cr genes were found in Aeromonas spp. from imported ornamental fish and koi carps from various geographical areas. Ornamental fish may represent a potential source of multiresistant bacteria and mobile genetic elements for the environment and for humans.

  11. Antibiotic resistance of lactic acid bacteria isolated from Chinese yogurts.

    PubMed

    Zhou, N; Zhang, J X; Fan, M T; Wang, J; Guo, G; Wei, X Y

    2012-09-01

    The aim of this study was to evaluate the susceptibility of 43 strains of lactic acid bacteria, isolated from Chinese yogurts made in different geographical areas, to 11 antibiotics (ampicillin, penicillin G, roxithromycin, chloramphenicol, tetracycline, chlortetracycline, lincomycin, kanamycin, streptomycin, neomycin, and gentamycin). The 43 isolates (18 Lactobacillus bulgaricus and 25 Streptococcus thermophilus) were identified at species level and were typed by random amplified polymorphic DNA analysis. Thirty-five genotypically different strains were detected and their antimicrobial resistance to 11 antibiotics was determined using the agar dilution method. Widespread resistance to ampicillin, chloramphenicol, chlortetracycline, tetracyclines, lincomycin, streptomycin, neomycin, and gentamycin was found among the 35 strains tested. All of the Strep. thermophilus strains tested were susceptible to penicillin G and roxithromycin, whereas 23.5 and 64.7% of Lb. bulgaricus strains, respectively, were resistant. All of the Strep. thermophilus and Lb. bulgaricus strains were found to be resistant to kanamycin. The presence of the corresponding resistance genes in the resistant isolates was investigated through PCR, with the following genes detected: tet(M) in 1 Lb. bulgaricus and 2 Strep. thermophilus isolates, ant(6) in 2 Lb. bulgaricus and 2 Strep. thermophilus isolates, and aph(3')-IIIa in 5 Lb. bulgaricus and 2 Strep. thermophilus isolates. The main threat associated with these bacteria is that they may transfer resistance genes to pathogenic bacteria, which has been a major cause of concern to human and animal health. To our knowledge, the aph(3')-IIIa and ant(6) genes were found in Lb. bulgaricus and Strep. thermophilus for the first time. Further investigations are required to analyze whether the genes identified in Lb. bulgaricus and Strep. thermophilus isolates might be horizontally transferred to other species.

  12. Apigenin as an anti-quinolone-resistance antibiotic.

    PubMed

    Morimoto, Yuh; Baba, Tadashi; Sasaki, Takashi; Hiramatsu, Keiichi

    2015-12-01

    We previously reported the first 'reverse antibiotic' (RA), nybomycin (NYB), which showed a unique antimicrobial activity against Staphylococcus aureus strains. NYB specifically suppressed the growth of quinolone-resistant S. aureus strains but was not effective against quinolone-susceptible strains. Although NYB was first reported in 1955, little was known about its unique antimicrobial activity because it was before the synthesis of the first quinolone ('old quinolone'), nalidixic acid, in 1962. Following our re-discovery of NYB, we looked for other RAs among natural substances that act on quinolone-resistant bacteria. Commercially available flavones were screened against S. aureus, including quinolone-resistant strains, and their minimum inhibitory concentrations (MICs) were compared using the microbroth dilution method. Some of the flavones screened showed stronger antimicrobial activity against quinolone-resistant strains than against quinolone-susceptible ones. Amongst them, apigenin (API) was the most potent in its RA activity. DNA cleavage assay showed that API inhibited DNA gyrase harbouring the quinolone resistance mutation gyrA(Ser84Leu) but did not inhibit 'wild-type' DNA gyrase that is sensitive to levofloxacin. An API-susceptible S. aureus strain Mu50 was also selected using agar plates containing 20mg/L API. Whole-genome sequencing of selected mutant strains was performed and frequent back-mutations (reverse mutations) were found among API-resistant strains derived from the API-susceptible S. aureus strains. Here we report that API represents another molecular class of natural antibiotic having RA activity against quinolone-resistant bacteria.

  13. Impact of anthropogenic activities on the dissemination of antibiotic resistance across ecological boundaries.

    PubMed

    Tripathi, Vijay; Cytryn, Eddie

    2017-02-28

    Antibiotics are considered to be one of the major medical breakthroughs in history. Nonetheless, over the past four decades, antibiotic resistance has reached alarming levels worldwide and this trend is expected to continue to increase, leading some experts to forecast the coming of a 'post-antibiotic' era. Although antibiotic resistance in pathogens is traditionally linked to clinical environments, there is a rising concern that the global propagation of antibiotic resistance is also associated with environmental reservoirs that are linked to anthropogenic activities such as animal husbandry, agronomic practices and wastewater treatment. It is hypothesized that the emergence and dissemination of antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) within and between environmental microbial communities can ultimately contribute to the acquisition of antibiotic resistance in human pathogens. Nonetheless, the scope of this phenomenon is not clear due to the complexity of microbial communities in the environment and methodological constraints that limit comprehensive in situ evaluation of microbial genomes. This review summarizes the current state of knowledge regarding antibiotic resistance in non-clinical environments, specifically focusing on the dissemination of antibiotic resistance across ecological boundaries and the contribution of this phenomenon to global antibiotic resistance.

  14. The drinking water treatment process as a potential source of affecting the bacterial antibiotic resistance.

    PubMed

    Bai, Xiaohui; Ma, Xiaolin; Xu, Fengming; Li, Jing; Zhang, Hang; Xiao, Xiang

    2015-11-15

    Two waterworks, with source water derived from the Huangpu or Yangtze River in Shanghai, were investigated, and the effluents were plate-screened for antibiotic-resistant bacteria (ARB) using five antibiotics: ampicillin (AMP), kanamycin (KAN), rifampicin (RFP), chloramphenicol (CM) and streptomycin (STR). The influence of water treatment procedures on the bacterial antibiotic resistance rate and the changes that bacteria underwent when exposed to the five antibiotics at concentration levels ranging from 1 to 100 μg/mL were studied. Multi-drug resistance was also analyzed using drug sensitivity tests. The results indicated that bacteria derived from water treatment plant effluent that used the Huangpu River rather than the Yangtze River as source water exhibited higher antibiotic resistance rates against AMP, STR, RFP and CM but lower antibiotic resistance rates against KAN. When the antibiotic concentration levels ranged from 1 to 10 μg/mL, the antibiotic resistance rates of the bacteria in the water increased as water treatment progressed. Biological activated carbon (BAC) filtration played a key role in increasing the antibiotic resistance rate of bacteria. Chloramine disinfection can enhance antibiotic resistance. Among the isolated ARB, 75% were resistant to multiple antibiotics. Ozone oxidation, BAC filtration and chloramine disinfection can greatly affect the relative abundance of bacteria in the community.

  15. Rapid Detection of Bacterial Antibiotic Resistance: Preliminary Evaluation of PCR Assays Targeting Tetracycline Resistance Genes

    DTIC Science & Technology

    2007-08-01

    Molecular analysis of rifampin resistance in Bacillus anthracis and Bacillus cereus . Antimicrobial Agents and Chemotherapy 46: 511-513 15 DSTO-TR...fever. Infections like inhalation anthrax and pneumonic plague, caused by Bacillus anthracis and Yersinia pestis, have to be treated with an effective...Table 1. Antibiotics commonly used against diseases caused by potential BW agents Organism Disease Antibiotics Bacillus anthracis Anthrax Ciprofloxacin

  16. Nano-technology for targeted drug delivery to combat antibiotic resistance.

    PubMed

    Sharma, Abhinay; Kumar Arya, Deepak; Dua, Meenakshi; Chhatwal, Gursharan Singh; Johri, Atul Kumar

    2012-11-01

    Several microbes have evolved clinically significant resistance against almost every available antibiotic. Yet the development of new classes of antibiotics has lagged far behind our growing need. Frequent and suboptimal use of antibiotics particularly in developing countries aggravated the problem by increasing the rate of resistance. Therefore, developing new and multidimensional strategies to combat microbial infections is warranted. These include i) modification of existing antibiotics, ii) searching new and novel antibiotics, iii) development and improvement of antibiotics carrier system to reduce amount and frequency of antibiotic doses, iv) development of targeted antibiotic delivery systems. Here, the authors discuss trends and development of nano-materials and alternative antimicrobials to solve the problem of antibiotic resistance.

  17. A Survey and Analysis of the American Public's Perceptions and Knowledge About Antibiotic Resistance

    PubMed Central

    Carter, Rebecca R.; Sun, Jiayang; Jump, Robin L. P.

    2016-01-01

    Background. Little is known about the American public's perceptions or knowledge about antibiotic-resistant bacteria or antibiotic misuse. We hypothesized that although many people recognize antibiotic resistance as a problem, they may not understand the relationship between antibiotic consumption and selection of resistant bacteria. Methods. We developed and tested a survey asking respondents about their perceptions and knowledge regarding appropriate antibiotic use. Respondents were recruited with the Amazon Mechanical Turk crowdsourcing platform. The survey, carefully designed to assess a crowd-sourced population, asked respondents to explain “antibiotic resistance” in their own words. Subsequent questions were multiple choice. Results. Of 215 respondents, the vast majority agreed that inappropriate antibiotic use contributes to antibiotic resistance (92%), whereas a notable proportion (70%) responded neutrally or disagreed with the statement that antibiotic resistance is a problem. Over 40% of respondents indicated that antibiotics were the best choice to treat a fever or a runny nose and sore throat. Major themes from the free-text responses included that antibiotic resistance develops by bacteria, or by the infection, or the body (ie, an immune response). Minor themes included antibiotic overuse and antibiotic resistance caused by bacterial adaptation or an immune response. Conclusions. Our findings indicate that the public is aware that antibiotic misuse contributes to antibiotic resistance, but many do not consider it to be an important problem. The free-text responses suggest specific educational targets, including the difference between an immune response and bacterial adaptation, to increase awareness and understanding of antibiotic resistance. PMID:27382598

  18. Biofilm processes in treating mariculture wastewater may be a reservoir of antibiotic resistance genes.

    PubMed

    Li, Shuai; Zhang, Shenghua; Ye, Chengsong; Lin, Wenfang; Zhang, Menglu; Chen, Lihua; Li, Jinmei; Yu, Xin

    2017-03-09

    Antibiotics are heavily used in Chinese mariculture, but only a small portion of the added antibiotics are absorbed by living creatures. Biofilm processes are universally used in mariculture wastewater treatment. In this study, removal of antibiotics (norfloxacin, rifampicin, and oxytetracycline) from wastewater by moving bed biofilm reactors (MBBRs) and the influence of antibiotics on reactor biofilm were investigated. The results demonstrated that there was no significant effect of sub-μg/L-sub-mg/L concentrations of antibiotics on TOC removal. Moreover, the relative abundance of antibiotic resistance genes (ARGs) and antibiotic resistance bacteria (ARB) in MBBR biofilm increased because of selective pressure of antibiotics. In addition, antibiotics decreased the diversity of the biofilm bacterial community and altered bacterial community structure. These findings provide an empirical basis for the development of appropriate practices for mariculture, and suggest that disinfection and advanced oxidation should be applied to eliminate antibiotics, ARGs, and ARB from mariculture wastewater.

  19. Bacteriophages as potential treatment option for antibiotic resistant bacteria.

    PubMed

    Bragg, Robert; van der Westhuizen, Wouter; Lee, Ji-Yun; Coetsee, Elke; Boucher, Charlotte

    2014-01-01

    The world is facing an ever-increasing problem with antibiotic resistant bacteria and we are rapidly heading for a post-antibiotic era. There is an urgent need to investigate alterative treatment options while there are still a few antibiotics left. Bacteriophages are viruses that specifically target bacteria. Before the development of antibiotics, some efforts were made to use bacteriophages as a treatment option, but most of this research stopped soon after the discovery of antibiotics. There are two different replication options which bacteriophages employ. These are the lytic and lysogenic life cycles. Both these life cycles have potential as treatment options. There are various advantages and disadvantages to the use of bacteriophages as treatment options. The main advantage is the specificity of bacteriophages and treatments can be designed to specifically target pathogenic bacteria while not negatively affecting the normal microbiota. There are various advantages to this. However, the high level of specificity also creates potential problems, the main being the requirement of highly specific diagnostic procedures. Another potential problem with phage therapy includes the development of immunity and limitations with the registration of phage therapy options. The latter is driving research toward the expression of phage genes which break the bacterial cell wall, which could then be used as a treatment option. Various aspects of phage therapy have been investigated in studies undertaken by our research group. We have investigated specificity of phages to various avian pathogenic E. coli isolates. Furthermore, the exciting NanoSAM technology has been employed to investigate bacteriophage replication and aspects of this will be discussed.

  20. Advanced treatment of urban wastewater by UV radiation: Effect on antibiotics and antibiotic-resistant E. coli strains.

    PubMed

    Rizzo, Luigi; Fiorentino, Antonino; Anselmo, Antonella

    2013-06-01

    Urban wastewater treatment plant (UWWTP) effluents are among the possible sources of antibiotics and antibiotic-resistant bacteria (ARB) spread into the environment. In this work, the effect of UV radiation on antibiotic-resistant Escherichia coli (E. coli) strains was compared with that of chlorination process. Under the investigated conditions, UV disinfection process resulted in a total inactivation after 60min of irradiation (1.25×10(4)μWscm(-2)) compared to 120min chlorine contact time (initial chlorine dose of 2mgL(-1)). Moreover, no change in E. coli strains' resistance to amoxicillin (AMX) (minimum inhibiting concentration (MIC)>256mgL(-1)) and sulfamethoxazole (SMZ) (MIC>1024mgL(-1)) could be observed after UV treatment, while the treatment affected resistance of the lower resistance strain to ciprofloxacin (CPX) (MIC decreased by 33% and 50% after 60 and 120min, respectively). Contrarily, chlorination process did not affect antibiotic resistance of the investigated E. coli strains. Finally, the effect of UV radiation on the mixture of three antibiotics was also investigated and photodegradation data fit quite well pseudo first order kinetic models with t1/2 values of 14, 20 and 25min for CPX, AMX and SMZ, respectively. According to these results, conventional disinfection processes may not be effective in the inactivation of ARB, and the simultaneous release of ARB and antibiotics at sub-lethal concentrations into UWWTP effluent may promote the development of resistance among bacteria in receiving water.

  1. CDC Vital Signs: Making Health Care Safer -- Protect Patients from Antibiotic Resistance

    MedlinePlus

    ... Press Kit Read the MMWR Science Clips Making Health Care Safer Protect patients from antibiotic resistance Language: English ... hours later. Know when to stop antibiotic treatment. Health care facility CEOs/ administrators can Prevent infections and their ...

  2. Density-dependent adaptive resistance allows swimming bacteria to colonize an antibiotic gradient.

    PubMed

    Hol, Felix J H; Hubert, Bert; Dekker, Cees; Keymer, Juan E

    2016-01-01

    During antibiotic treatment, antibiotic concentration gradients develop. Little is know regarding the effects of antibiotic gradients on populations of nonresistant bacteria. Using a microfluidic device, we show that high-density motile Escherichia coli populations composed of nonresistant bacteria can, unexpectedly, colonize environments where a lethal concentration of the antibiotic kanamycin is present. Colonizing bacteria establish an adaptively resistant population, which remains viable for over 24 h while exposed to the antibiotic. Quantitative analysis of multiple colonization events shows that collectively swimming bacteria need to exceed a critical population density in order to successfully colonize the antibiotic landscape. After colonization, bacteria are not dormant but show both growth and swimming motility under antibiotic stress. Our results highlight the importance of motility and population density in facilitating adaptive resistance, and indicate that adaptive resistance may be a first step to the emergence of genetically encoded resistance in landscapes of antibiotic gradients.

  3. Resistance to antibiotics targeted to the bacterial cell wall.

    PubMed

    Nikolaidis, I; Favini-Stabile, S; Dessen, A

    2014-03-01

    Peptidoglycan is the main component of the bacterial cell wall. It is a complex, three-dimensional mesh that surrounds the entire cell and is composed of strands of alternating glycan units crosslinked by short peptides. Its biosynthetic machinery has been, for the past five decades, a preferred target for the discovery of antibacterials. Synthesis of the peptidoglycan occurs sequentially within three cellular compartments (cytoplasm, membrane, and periplasm), and inhibitors of proteins that catalyze each stage have been identified, although not all are applicable for clinical use. A number of these antimicrobials, however, have been rendered inactive by resistance mechanisms. The employment of structural biology techniques has been instrumental in the understanding of such processes, as well as the development of strategies to overcome them. This review provides an overview of resistance mechanisms developed toward antibiotics that target bacterial cell wall precursors and its biosynthetic machinery. Strategies toward the development of novel inhibitors that could overcome resistance are also discussed.

  4. Efficient removal of antibiotics in surface-flow constructed wetlands, with no observed impact on antibiotic resistance genes.

    PubMed

    Berglund, Björn; Khan, Ghazanfar Ali; Weisner, Stefan E B; Ehde, Per Magnus; Fick, Jerker; Lindgren, Per-Eric

    2014-04-01

    Recently, there have been growing concerns about pharmaceuticals including antibiotics as environmental contaminants. Antibiotics of concentrations commonly encountered in wastewater have been suggested to affect bacterial population dynamics and to promote dissemination of antibiotic resistance. Conventional wastewater treatment processes do not always adequately remove pharmaceuticals causing environmental dissemination of low levels of these compounds. Using constructed wetlands as an additional treatment step after sewage treatment plants have been proposed as a cheap alternative to increase reduction of wastewater contaminants, however this means that the natural microbial community of the wetlands becomes exposed to elevated levels of antibiotics. In this study, experimental surface-flow wetlands in Sweden were continuously exposed to antibiotics of concentrations commonly encountered in wastewater. The aim was to assess the antibiotic removal efficiency of constructed wetlands and to evaluate the impact of low levels of antibiotics on bacterial diversity, resistance development and expression in the wetland bacterial community. Antibiotic concentrations were measured using liquid chromatography-mass spectrometry and the effect on the bacterial diversity was assessed with 16S rRNA-based denaturing gradient gel electrophoresis. Real-time PCR was used to detect and quantify antibiotic resistance genes and integrons in the wetlands, during and after the exposure period. The results indicated that the antibiotic removal efficiency of constructed wetlands was comparable to conventional wastewater treatment schemes. Furthermore, short-term treatment of the constructed wetlands with environmentally relevant concentrations (i.e. 100-2000 ng×l(-1)) of antibiotics did not significantly affect resistance gene concentrations, suggesting that surface-flow constructed wetlands are well-suited for wastewater treatment purposes.

  5. In vitro selective antibiotic concentrations of beta-lactams for penicillin-resistant Streptococcus pneumoniae populations.

    PubMed Central

    Negri, M C; Morosini, M I; Loza, E; Baquero, F

    1994-01-01

    Therapeutic regimens containing beta-lactam antibiotics are selecting penicillin-resistant Streptococcus pneumoniae populations all over the world. The selective pressure after 4 h of exposure to different concentrations of amoxicillin, cefixime, cefuroxime, and cefotaxime for low-level or high-level penicillin-resistant S. pneumoniae was evaluated in an in vitro model with mixed populations with penicillin susceptibilities of 0.015, 0.5, 1, and 2 micrograms/ml. The antibiotic concentration selecting for low-level resistance strongly reduced the susceptible population. Increasing antibiotic concentrations tended to decrease the total proportion of penicillin-resistant bacteria because of reduced numbers of the low-level-resistant population. The antibiotic concentration selecting for high-level resistance produced fewer resistant populations, but most of the organisms selected represented high-level resistance. In general, amoxicillin was a good selector for the low-level-resistant population and a poor selector for high-level resistance; cefuroxime and cefotaxime were poor selectors for low-level resistance and better selectors than amoxicillin for high-level penicillin resistance. Cefixime was the best selector of low-level penicillin resistance. When only resistant populations were mixed, the strains with high-level resistance were selected even at low antibiotic concentrations. Determination of the effects of selective antibiotic concentrations on mixed cultures of bacteria expressing different antibiotic resistance levels may help researchers to understand the ecology and epidemiology of penicillin-resistant S. pneumoniae populations. PMID:8141563

  6. Clostridium difficile infection: update on emerging antibiotic treatment options and antibiotic resistance

    PubMed Central

    Shah, Dhara; Dang, Minh-Duc; Hasbun, Rodrigo; Koo, Hoonmo L; Jiang, Zhi-Dong; DuPont, Herbert L; Garey, Kevin W

    2010-01-01

    Clostridium difficile infection (CDI) is the most common cause of identifiable diarrhea in hospitalized patients. The incidence and severity of CDIs are increasing. The increased incidence and severity of the disease has sparked interest in the optimal treatment of CDI as well as the use of new therapies and drug discovery. Current treatment strategies are inadequate with decreased response rates to metronidazole, and high recurrence rates with the use of metronidazole and oral vancomycin. Although incidence rates continue to be low, in vitro resistance to antibiotics used for the treatment of CDI has been noted. Recently, important data has emerged on new anti-C. difficile antibiotics such as rifaximin, rifalazil, fidaxomicin, nitazoxanide, tigecycline and ramoplanin. The purpose of this review is to provide an update on the in vitro susceptibility and new antibiotic treatment options for CDI. This review will focus primarily on scientific studies published in the last 36 months in order to provide an up-to-date review on the topic. PMID:20455684

  7. Behavior of antibiotics and antibiotic resistance genes in eco-agricultural system: A case study.

    PubMed

    Cheng, Weixiao; Li, Jianan; Wu, Ying; Xu, Like; Su, Chao; Qian, Yanyun; Zhu, Yong-Guan; Chen, Hong

    2016-03-05

    This study aims to determine abundance and persistence of antibiotics and antibiotic resistance genes (ARGs) in eco-agricultural system (EAS), which starts from swine feces to anaerobic digestion products, then application of anaerobic digestion solid residue (ADSR) and anaerobic digestion liquid residue (ADLR) to the soil to grow ryegrass, one of swine feed. Oxytetracycline had the highest concentration in manure reaching up to 138.7 mg/kg. Most of antibiotics could be effectively eliminated by anaerobic digestion and removal rates ranged from 11% to 86%. ARGs abundance fluctuated within EAS. TetQ had the highest relative abundance and the relative abundance of tetG had the least variation within the system, which indicates that tetG is persistent in the agricultural environment and requires more attention. Compared to the relative abundance in manure, tetC and tetM increased in biogas residue while three ribosomal protection proteins genes (tetO, tetQ, tetW) decreased (p<0.05), with other genes showing no significant change after anaerobic fermentation (p>0.05). Most ARGs in downstream components (soils and fishpond) of EAS showed significantly higher relative abundance than the control agricultural system (p<0.05), except for tetG and sulI.

  8. Antibiotic-resistant genes and antibiotic-resistant bacteria in the effluent of urban residential areas, hospitals, and a municipal wastewater treatment plant system.

    PubMed

    Li, Jianan; Cheng, Weixiao; Xu, Like; Strong, P J; Chen, Hong

    2015-03-01

    In this study, we determined the abundance of 8 antibiotics (3 tetracyclines, 4 sulfonamides, and 1 trimethoprim), 12 antibiotic-resistant genes (10 tet, 2 sul), 4 antibiotic-resistant bacteria (tetracycline, sulfamethoxazole, and combined resistance), and class 1 integron integrase gene (intI1) in the effluent of residential areas, hospitals, and municipal wastewater treatment plant (WWTP) systems. The concentrations of total/individual targets (antibiotics, genes, and bacteria) varied remarkably among different samples, but the hospital samples generally had a lower abundance than the residential area samples. The WWTP demonstrated removal efficiencies of 50.8% tetracyclines, 66.8% sulfonamides, 0.5 logs to 2.5 logs tet genes, and less than 1 log of sul and intI1 genes, as well as 0.5 log to 1 log removal for target bacteria. Except for the total tetracycline concentration and the proportion of tetracycline-resistant bacteria (R (2) = 0.330, P < 0.05), there was no significant correlation between antibiotics and the corresponding resistant bacteria (P > 0.05). In contrast, various relationships were identified between antibiotics and antibiotic resistance genes (P < 0.05). Tet (A) and tet (B) displayed noticeable relationships with both tetracycline and combined antibiotic-resistant bacteria (P < 0.01).

  9. Antibiotic resistance in Aeromonas upstream and downstream of a water resource recovery facility.

    PubMed

    Cisar, Cindy R; Henderson, Samantha K; Askew, Maegan L; Risenhoover, Hollie G; McAndrews, Chrystle R; Kennedy, S Dawn; Paine, C Sue

    2014-09-01

    Aeromonas strains isolated from sediments upstream and downstream of a water resource recovery facility (WRRF) over a two-year time period were tested for susceptibility to 13 antibiotics. Incidence of resistance to antibiotics, antibiotic resistance phenotypes, and diversity (based on resistance phenotypes) were compared in the two populations. At the beginning of the study, the upstream and downstream Aeromonas populations were different for incidence of antibiotic resistance (p < 0.01), resistance phenotypes (p < 0.005), and diversity. However, these differences declined over time and were not significant at the end of the study. These results (1) indicate that antibiotic resistance in Aeromonas in stream sediments fluctuates considerably over time and (2) suggest that WRRF effluent does not, when examined over the long- term, affect antibiotic resistance in Aeromonas in downstream sediment.

  10. Status Report from the Scientific Panel on Antibiotic Use in Dermatology of the American Acne and Rosacea Society: Part 1: Antibiotic Prescribing Patterns, Sources of Antibiotic Exposure, Antibiotic Consumption and Emergence of Antibiotic Resistance, Impact of Alterations in Antibiotic Prescribing, and Clinical Sequelae of Antibiotic Use.

    PubMed

    Del Rosso, James Q; Webster, Guy F; Rosen, Ted; Thiboutot, Diane; Leyden, James J; Gallo, Richard; Walker, Clay; Zhanel, George; Eichenfield, Lawrence

    2016-04-01

    Oral and topical antibiotics are commonly prescribed in dermatologie practice, often for noninfectious disorders, such as acne vulgaris and rosacea. Concerns related to antibiotic exposure from both medical and nonmedical sources require that clinicians consider in each case why and how antibiotics are being used and to make appropriate adjustments to limit antibiotic exposure whenever possible. This first article of a three-part series discusses prescribing patterns in dermatology, provides an overview of sources of antibiotic exposure, reviews the relative correlations between the magnitude of antibiotic consumption and emergence of antibiotic resistance patterns, evaluates the impact of alterations in antibiotic prescribing, and discusses the potential relevance and clinical sequelae of antibiotic use, with emphasis on how antibiotics are used in dermatology.

  11. Continental-scale pollution of estuaries with antibiotic resistance genes.

    PubMed

    Zhu, Yong-Guan; Zhao, Yi; Li, Bing; Huang, Chu-Long; Zhang, Si-Yu; Yu, Shen; Chen, Yong-Shan; Zhang, Tong; Gillings, Michael R; Su, Jian-Qiang

    2017-01-30

    Antibiotic resistance genes (ARGs) have moved from the environmental resistome into human commensals and pathogens, driven by human selection with antimicrobial agents. These genes have increased in abundance in humans and domestic animals, to become common components of waste streams. Estuarine habitats lie between terrestrial/freshwater and marine ecosystems, acting as natural filtering points for pollutants. Here, we have profiled ARGs in sediments from 18 estuaries over 4,000 km of coastal China using high-throughput quantitative polymerase chain reaction, and investigated their relationship with bacterial communities, antibiotic residues and socio-economic factors. ARGs in estuarine sediments were diverse and abundant, with over 200 different resistance genes being detected, 18 of which were found in all 90 sediment samples. The strong correlations of identified resistance genes with known mobile elements, network analyses and partial redundancy analysis all led to the conclusion that human activity is responsible for the abundance and dissemination of these ARGs. Such widespread pollution with xenogenetic elements has environmental, agricultural and medical consequences.

  12. Bypass of genetic constraints during mutator evolution to antibiotic resistance.

    PubMed

    Couce, Alejandro; Rodríguez-Rojas, Alexandro; Blázquez, Jesús

    2015-04-07

    Genetic constraints can block many mutational pathways to optimal genotypes in real fitness landscapes, yet the extent to which this can limit evolution remains to be determined. Interestingly, mutator bacteria elevate only specific types of mutations, and therefore could be very sensitive to genetic constraints. Testing this possibility is not only clinically relevant, but can also inform about the general impact of genetic constraints in adaptation. Here, we evolved 576 populations of two mutator and one wild-type Escherichia coli to doubling concentrations of the antibiotic cefotaxime. All strains carried TEM-1, a β-lactamase enzyme well known by its low availability of mutational pathways. Crucially, one of the mutators does not elevate any of the relevant first-step mutations known to improve cefatoximase activity. Despite this, both mutators displayed a similar ability to evolve more than 1000-fold resistance. Initial adaptation proceeded in parallel through general multi-drug resistance mechanisms. High-level resistance, in contrast, was achieved through divergent paths; with the a priori inferior mutator exploiting alternative mutational pathways in PBP3, the target of the antibiotic. These results have implications for mutator management in clinical infections and, more generally, illustrate that limits to natural selection in real organisms are alleviated by the existence of multiple loci contributing to fitness.

  13. [Presence of resistance factors to antibiotics in multiresistant enterobacteria].

    PubMed

    Parada, J L; De Nardo, J; Rebollo, M; Marcenac, F; Fernández, A

    1977-01-01

    The present study was carried out with 111 multiresistant pathogenic strains of enterobacterias isolated from different sources with increased resistance to three or more antibiotics. Among the identified species are included E. coli, Shigella sp., Salmonella oranienburg, Klebsiella pneumoniae and Citrobacter freundii. In general, the minimal inhibitory concentration of antibiotics was above 100 microgram/ml and in some cases it was superior to 1000 microgram/ml. Resistance transfer factors were detected in 72% of the strains; 33% movilized the complete pattern of resistance and 67% did it partially because some of the determinants were not transfered. The Citrobacter strains show a high frequency of transference (10(-1)), while for the others species it was in the order of 10(-2)--10(-3). The use of a multi-inoculator allows to perform in a simple way the preliminar evaluation about the presence or absence of R transfer factors in multiresistant strains. This technique has shown good correlation with the data obtained by the usual dilution and plating method.

  14. Biophysical separation of Staphylococcus epidermidis strains based on antibiotic resistance

    PubMed Central

    Jones, Paul V.; Huey, Shannon; Davis, Paige; McLemore, Ryan; McLaren, Alex

    2015-01-01

    Electrophoretic and dielectrophoretic approaches to separations can provide unique capabilities. In the past, capillary and microchip-based approaches to electrophoresis have demonstrated extremely high-resolution separations. More recently, dielectrophoretic systems have shown excellent results for the separation of bioparticles. Here we demonstrate resolution of a difficult pair of targets: gentamicin resistant and susceptible strains of Staphylococcus epidermidis. This separation has significant potential implications for healthcare. This establishes a foundation for biophysical separations as a direct diagnostic tool, potentially improving nearly every figure of merit for diagnostics and antibiotic stewardship. The separations are performed on a modified gradient insulator-based dielectrophoresis (g-iDEP) system and demonstrate that the presence of antibiotic resistance enzymes (or secondary effects) produces a sufficient degree of electrophysical difference to allow separation. The differentiating factor is the ratio of electrophoretic to dielectrophoretic mobilities. This factor is 4.6 ± 0.6 × 109 V m–2 for the resistant strain, versus 9.2 ± 0.4 × 109 V m–2 for the susceptible strain. Using g-iDEP separation, this difference produces clear and easily discerned differentiation of the two strains. PMID:26086047

  15. Molecular detection of antibiotic resistance genes from positive blood cultures.

    PubMed

    Hindiyeh, Musa Y; Smollan, Gill; Gefen-Halevi, Shiraz; Mendelson, Ella; Keller, Nathan

    2015-01-01

    Rapid detection of the bacterial causative agent causing sepsis must be coupled with rapid identification of the antibiotic resistant mechanism that the pathogen might possess. Real-time PCR (qPCR)-based assays have been extensively utilized in the clinical microbiology field as diagnostic tools for the rapid detection of specific nucleic acid (NA) targets. In this chapter, we will discuss the technical aspects of using an internally controlled qPCR assay for the rapid detection of Klebsiella pneumoniae carbapenemase gene (bla KPC) in positive Bactec blood culture bottles. The multiplex qPCR (bla KPC/RNase P) utilizes specific primers and probes for the detection of the bacterial carbapenem resistance mechanism, bla KPC gene, and the internal control RNase P. The internal control of the qPCR assay is vital for detecting any inhibitors that are well known to be present in the blood culture bottles. Rapid detection of the antibiotic resistant mechanism present in the bacterial pathogen causing sepsis can help in better managing patients' infection.

  16. Putrescine reduces antibiotic-induced oxidative stress as a mechanism of modulation of antibiotic resistance in Burkholderia cenocepacia.

    PubMed

    El-Halfawy, Omar M; Valvano, Miguel A

    2014-07-01

    Communication of antibiotic resistance among bacteria via small molecules is implicated in transient reduction of bacterial susceptibility to antibiotics, which could lead to therapeutic failures aggravating the problem of antibiotic resistance. Released putrescine from the extremely antibiotic-resistant bacterium Burkholderia cenocepacia protects less-resistant cells from different species against the antimicrobial peptide polymyxin B (PmB). Exposure of B. cenocepacia to sublethal concentrations of PmB and other bactericidal antibiotics induces reactive oxygen species (ROS) production and expression of the oxidative stress response regulator OxyR. We evaluated whether putrescine alleviates antibiotic-induced oxidative stress. The accumulation of intracellular ROS, such as superoxide ion and hydrogen peroxide, was assessed fluorometrically with dichlorofluorescein diacetate, while the expression of OxyR and putrescine synthesis enzymes was determined in luciferase assays using chromosomal promoter-lux reporter system fusions. We evaluated wild-type and isogenic deletion mutant strains with defects in putrescine biosynthesis after exposure to sublethal concentrations of PmB and other bactericidal antibiotics. Exogenous putrescine protected against oxidative stress induced by PmB and other antibiotics, whereas reduced putrescine synthesis resulted in increased ROS generation and a parallel increased sensitivity to PmB. Of the 3 B. cenocepacia putrescine-synthesizing enzymes, PmB induced only BCAL2641, an ornithine decarboxylase. This study reveals BCAL2641 as a critical component of the putrescine-mediated communication of antibiotic resistance and as a plausible target for designing inhibitors that would block the communication of such resistance among different bacteria, ultimately reducing the window of therapeutic failure in treating bacterial infections.

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

    PubMed

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

    2015-08-01

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

  18. Low Temperature and Modified Atmosphere: Hurdles for Antibiotic Resistance Transfer?

    PubMed

    Van Meervenne, Eva; Van Coillie, Els; Van Weyenberg, Stephanie; Boon, Nico; Herman, Lieve; Devlieghere, Frank

    2015-12-01

    Food is an important dissemination route for antibiotic-resistant bacteria. Factors used during food production and preservation may contribute to the transfer of antibiotic resistance genes, but research on this subject is scarce. In this study, the effect of temperature (7 to 37°C) and modified atmosphere packaging (air, 50% CO2-50% N2, and 100% N2) on antibiotic resistance transfer from Lactobacillus sakei subsp. sakei to Listeria monocytogenes was evaluated. Filter mating was performed on nonselective agar plates with high-density inocula. A more realistic setup was created by performing modified atmosphere experiments on cooked ham using high-density and low-density inocula. Plasmid transfer was observed between 10 and 37°C, with plasmid transfer also observed at 7°C during a prolonged incubation period. When high-density inocula were used, transconjugants were detected, both on agar plates and cooked ham, under the three atmospheres (air, 50% CO2-50% N2, and 100% N2) at 7°C. This yielded a median transfer ratio (number of transconjugants/number of recipients) with an order of magnitude of 10(-4) to 10(-6). With low-density inocula, transfer was only detected under the 100% N2 atmosphere after 10-day incubation at 7°C, yielding a transfer ratio of 10(-5). Under this condition, the highest bacterial density was obtained. The results indicate that low temperature and modified atmosphere packaging, two important hurdles in the food industry, do not necessarily prevent plasmid transfer from Lactobacillus sakei subsp. sakei to Listeria monocytogenes.

  19. Novel target sites in bacteria for overcoming antibiotic resistance.

    PubMed

    Black, Michael T; Hodgson, John

    2005-07-29

    Resistance to marketed antibiotics continues to increase. During the last 10 years some 200 bacterial genome sequences have become available, giving rise to expectations that genomics would provide a plethora of novel targets and hence a flood of new therapeutic agents. Contrary to some predictions the genomic effort has yet to yield a substantial number of novel class agents in clinical development. What are the reasons for the differences between expectations and reality? This article reviews what has been achieved in the exploitation of bacterial genomes for the discovery of novel antibacterials.

  20. Quantifying Attachment and Antibiotic Resistance of from Conventional and Organic Swine Manure.

    PubMed

    Zwonitzer, Martha R; Soupir, Michelle L; Jarboe, Laura R; Smith, Douglas R

    2016-03-01

    Broad-spectrum antibiotics are often administered to swine, contributing to the occurrence of antibiotic-resistant bacteria in their manure. During land application, the bacteria in swine manure preferentially attach to particles in the soil, affecting their transport in overland flow. However, a quantitative understanding of these attachment mechanisms is lacking, and their relationship to antibiotic resistance is unknown. The objective of this study is to examine the relationships between antibiotic resistance and attachment to very fine silica sand in collected from swine manure. A total of 556 isolates were collected from six farms, two organic and four conventional (antibiotics fed prophylactically). Antibiotic resistance was quantified using 13 antibiotics at three minimum inhibitory concentrations: resistant, intermediate, and susceptible. Of the 556 isolates used in the antibiotic resistance assays, 491 were subjected to an attachment assay. Results show that isolates from conventional systems were significantly more resistant to amoxicillin, ampicillin, chlortetracycline, erythromycin, kanamycin, neomycin, streptomycin, tetracycline, and tylosin ( < 0.001). Results also indicate that isolated from conventional systems attached to very fine silica sand at significantly higher levels than those from organic systems ( < 0.001). Statistical analysis showed that a significant relationship did not exist between antibiotic resistance levels and attachment in from conventional systems but did for organic systems ( < 0.001). Better quantification of these relationships is critical to understanding the behavior of in the environment and preventing exposure of human populations to antibiotic-resistant bacteria.

  1. Aquaculture changes the profile of antibiotic resistance and mobile genetic element associated genes in Baltic Sea sediments.

    PubMed

    Muziasari, Windi I; Pärnänen, Katariina; Johnson, Timothy A; Lyra, Christina; Karkman, Antti; Stedtfeld, Robert D; Tamminen, Manu; Tiedje, James M; Virta, Marko

    2016-04-01

    Antibiotics are commonly used in aquaculture and they can change the environmental resistome by increasing antibiotic resistance genes (ARGs). Sediment samples were collected from two fish farms located in the Northern Baltic Sea, Finland, and from a site outside the farms (control). The sediment resistome was assessed by using a highly parallel qPCR array containing 295 primer sets to detect ARGs, mobile genetic elements and the 16S rRNA gene. The fish farm resistomes were enriched in transposon and integron associated genes and in ARGs encoding resistance to antibiotics which had been used to treat fish at the farms. Aminoglycoside resistance genes were also enriched in the farm sediments despite the farms not having used aminoglycosides. In contrast, the total relative abundance values of ARGs were higher in the control sediment resistome and they were mainly genes encoding efflux pumps followed by beta-lactam resistance genes, which are found intrinsically in many bacteria. This suggests that there is a natural Baltic sediment resistome. The resistome associated with fish farms can be from native ARGs enriched by antibiotic use at the farms and/or from ARGs and mobile elements that have been introduced by fish farming.

  2. Antibiotics

    MedlinePlus

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

  3. [Antibiotic efficacies of combined uses of arbekacin and various antibiotics against methicillin-resistant Staphylococcus aureus].

    PubMed

    Deguchi, K; Yokota, N; Koguchi, M; Suzuki, Y; Suzuki, K; Fukayama, S; Ishihara, R; Oda, S

    1994-06-01

    Efficacies of combined uses of arbekacin(ABK) with other antibiotics against between 57 and 76 clinically isolated methicillin-resistant Staphylococcus aureus(MRSA) were examined. Other antibiotics tested were fosfomycin(FOM), 5 cephems(CEPs), 2 penicillins(PCs) and imipenem. Percentages of strains that grew at various combination of serially diluted drugs in a microdilution method were scored, and for each pair of drugs > or = MIC50 or > or = MIC90 was determined. FIC-indices were calculated at > or = MIC50. Bacterial growth was inhibited by low concentrations of ABK dose-dependently, while most of the strains tested were resistant to 9 other drugs. FIC-indices with ABK were lowest when used together with ampicillin (ABPC) (0.516) followed by combinations with cefotiam (CTM) and cefuzonam (CZON) (each, 0.53), and FOM (0.625). When combined with 0.5 microgram/ml of ABK, 0.5 microgram/ml of ABPC inhibited more than 50% of MRSA strains. CTM or CZON in combination with the same amount of ABK to 2 micrograms/ml inhibited more than 50% of MRSA. Thus ABPC was found to be the most efficient in combined use with ABK to inhibit clinical MRSA strains.

  4. Antibiotic Adjuvants: Diverse Strategies for Controlling Drug-Resistant Pathogens

    PubMed Central

    Gill, Erin E; Franco, Octavio L; Hancock, Robert E W

    2015-01-01

    The growing number of bacterial pathogens that are resistant to numerous antibiotics is a cause for concern around the globe. There have been no new broad-spectrum antibiotics developed in the last 40 years, and the drugs we have currently are quickly becoming ineffective. In this article, we explore a range of therapeutic strategies that could be employed in conjunction with antibiotics and may help to prolong the life span of these life-saving drugs. Discussed topics include antiresistance drugs, which are administered to potentiate the effects of current antimicrobials in bacteria where they are no longer (or never were) effective; antivirulence drugs, which are directed against bacterial virulence factors; host-directed therapies, which modulate the host's immune system to facilitate infection clearance; and alternative treatments, which include such therapies as oral rehydration for diarrhea, phage therapy, and probiotics. All of these avenues show promise for the treatment of bacterial infections and should be further investigated to explore their full potential in the face of a postantibiotic era. PMID:25393203

  5. Antibiotics Quiz

    MedlinePlus

    ... National Activities Get Smart: Know When Antibiotics Work Strategies and Plans Related CDC Education Programs Global Activities Measuring Outpatient Antibiotic Prescribing Tracking Antibiotic-Resistant ...

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

    PubMed Central

    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. PMID:22858695

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

    PubMed

    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.

  8. Nanoparticles functionalized with ampicillin destroy multiple-antibiotic-resistant isolates of Pseudomonas aeruginosa and Enterobacter aerogenes and methicillin-resistant Staphylococcus aureus.

    PubMed

    Brown, Ashley N; Smith, Kathryn; Samuels, Tova A; Lu, Jiangrui; Obare, Sherine O; Scott, Maria E

    2012-04-01

    We show here that silver nanoparticles (AgNP) were intrinsically antibacterial, whereas gold nanoparticles (AuNP) were antimicrobial only when ampicillin was bound to their surfaces. Both AuNP and AgNP functionalized with ampicillin were effective broad-spectrum bactericides against Gram-negative and Gram-positive bacteria. Most importantly, when AuNP and AgNP were functionalized with ampicillin they became potent bactericidal agents with unique properties that subverted antibiotic resistance mechanisms of multiple-drug-resistant bacteria.

  9. Applying the emergency risk management process to tackle the crisis of antibiotic resistance

    PubMed Central

    Dominey-Howes, Dale; Bajorek, Beata; Michael, Carolyn A.; Betteridge, Brittany; Iredell, Jonathan; Labbate, Maurizio

    2015-01-01

    We advocate that antibiotic resistance be reframed as a disaster risk management problem. Antibiotic-resistant infections represent a risk to life as significant as other commonly occurring natural disasters (e.g., earthquakes). Despite efforts by global health authorities, antibiotic resistance continues to escalate. Therefore, new approaches and expertise are needed to manage the issue. In this perspective we: (1) make a call for the emergency management community to recognize the antibiotic resistance risk and join in addressing this problem; (2) suggest using the risk management process to help tackle antibiotic resistance; (3) show why this approach has value and why it is different to existing approaches; and (4) identify public perception of antibiotic resistance as an important issue that warrants exploration. PMID:26388864

  10. A modeling framework for the evolution and spread of antibiotic resistance: literature review and model categorization.

    PubMed

    Spicknall, Ian H; Foxman, Betsy; Marrs, Carl F; Eisenberg, Joseph N S

    2013-08-15

    Antibiotic-resistant infections complicate treatment and increase morbidity and mortality. Mathematical modeling has played an integral role in improving our understanding of antibiotic resistance. In these models, parameter sensitivity is often assessed, while model structure sensitivity is not. To examine the implications of this, we first reviewed the literature on antibiotic-resistance modeling published between 1993 and 2011. We then classified each article's model structure into one or more of 6 categories based on the assumptions made in those articles regarding within-host and population-level competition between antibiotic-sensitive and antibiotic-resistant strains. Each model category has different dynamic implications with respect to how antibiotic use affects resistance prevalence, and therefore each may produce different conclusions about optimal treatment protocols that minimize resistance. Thus, even if all parameter values are correctly estimated, inferences may be incorrect because of the incorrect selection of model structure. Our framework provides insight into model selection.

  11. Genome-wide analysis captures the determinants of the antibiotic cross-resistance interaction network

    PubMed Central

    Lázár, Viktória; Nagy, István; Spohn, Réka; Csörgő, Bálint; Györkei, Ádám; Nyerges, Ákos; Horváth, Balázs; Vörös, Andrea; Busa-Fekete, Róbert; Hrtyan, Mónika; Bogos, Balázs; Méhi, Orsolya; Fekete, Gergely; Szappanos, Balázs; Kégl, Balázs; Papp, Balázs; Pál, Csaba

    2014-01-01

    Understanding how evolution of antimicrobial resistance increases resistance to other drugs is a challenge of profound importance. By combining experimental evolution and genome sequencing of 63 laboratory-evolved lines, we charted a map of cross-resistance interactions between antibiotics in Escherichia coli, and explored the driving evolutionary principles. Here, we show that (1) convergent molecular evolution is prevalent across antibiotic treatments, (2) resistance conferring mutations simultaneously enhance sensitivity to many other drugs and (3) 27% of the accumulated mutations generate proteins with compromised activities, suggesting that antibiotic adaptation can partly be achieved without gain of novel function. By using knowledge on antibiotic properties, we examined the determinants of cross-resistance and identified chemogenomic profile similarity between antibiotics as the strongest predictor. In contrast, cross-resistance between two antibiotics is independent of whether they show synergistic effects in combination. These results have important implications on the development of novel antimicrobial strategies. PMID:25000950

  12. Community perceptions of infectious diseases, antibiotic use and antibiotic resistance in context of environmental changes: a study in Odisha, India

    PubMed Central

    Sahoo, Krushna Chandra; Tamhankar, Ashok J.; Johansson, Eva; Stålsby Lundborg, Cecilia

    2012-01-01

    Abstract Background  The public health impact of environmental changes and the faceless threat of antibiotic resistance are currently among the top global health challenges. Community understanding of health, diseases and medicines in relation to the changing environment is necessary to mitigate the impact of these changes on health and for prudent use of antibiotics. Objective  The objective is to explore community perceptions of infectious diseases, antibiotic use and antibiotic resistance in the context of environmental changes. Methods  A qualitative study was conducted among community members with various backgrounds in education, gender, age and occupation of two districts of Odisha, India. Eight focus groups discussions and ten individual interviews were conducted. Data were analysed using content analysis. Results  Two themes emerged: ‘Interpretation of infectious diseases and health hazards in the context of environmental changes’, and ‘Understanding of antibiotic use and its consequences for resistance development and the environment’. The participants perceived that nowadays there is irregularity in the occurrence of seasons, particularly an increase in average temperature, which is influencing health. Participants’ perceptions of infectious diseases, antibiotic use and resistance varied according to their social environment. Furthermore, they perceived that improved sanitation, choice of alternative medicine and awareness and education on prudent use of antibiotics are probably some ways to prevent antibiotic resistance. Conclusions  The participants perceived that climate variability is increasing and that this has health consequences for the community. They also hypothesized an interrelationship between the environment, infectious diseases and medicine use, particularly antibiotics. This is helpful for further empirical studies. PMID:22583645

  13. Occurrence of antibiotic resistance and characterization of resistant genes and integrons in Enterobacteriaceae isolated from integrated fish farms south China

    USGS Publications Warehouse

    Su, Hao-Chang; Ying, Guang-Guo; Tao, Ran; Zhang, Rui-Quan; Fogarty, Lisa R.; Kolpin, Dana W.

    2011-01-01

    Antibiotics are still widely applied in animal husbandry to prevent diseases and used as feed additives to promote animal growth. This could result in antibiotic resistance to bacteria and antibiotic residues in animals. In this paper, Enterobacteriaceae isolated from four integrated fish farms in Zhongshan, South China were tested for antibiotic resistance, tetracycline resistance genes, sulfonamide resistance genes, and class 1 integrons. The Kirby-Bauer disk diffusion method and polymerase chain reaction (PCR) assays were carried out to test antibiotic susceptibility and resistance genes, respectively. Relatively high antibiotic resistance frequencies were found, especially for ampicillin (80%), tetracycline (52%), and trimethoprim (50%). Out of 203 Enterobacteriaceae isolates, 98.5% were resistant to one or more antibiotics tested. Multiple antibiotic resistance (MAR) was found highest in animal manures with a MAR index of 0.56. Tetracycline resistance genes (tet(A), tet(C)) and sulfonamide resistance genes (sul2) were detected in more than 50% of the isolates. The intI1 gene was found in 170 isolates (83.7%). Both classic and non-classic class 1 integrons were found. Four genes, aadA5, aadA22, dfr2, and dfrA17, were detected. To our knowledge, this is the first report for molecular characterization of antibiotic resistance genes in Enterobacteriaceae isolated from integrated fish farms in China and the first time that gene cassette array dfrA17-aadA5 has been detected in such fish farms. Results of this study indicated that fish farms may be a reservoir of highly diverse and abundant antibiotic resistant genes and gene cassettes. Integrons may play a key role in multiple antibiotic resistances posing potential health risks to the general public and aquaculture.

  14. Antibiotic-resistant fecal bacteria, antibiotics, and mercury in surface waters of Oakland County, Michigan, 2005-2006

    USGS Publications Warehouse

    Fogarty, Lisa R.; Duris, Joseph W.; Crowley, Suzanne L.; Hardigan, Nicole

    2007-01-01

    Water samples collected from 20 stream sites in Oakland and Macomb Counties, Mich., were analyzed to learn more about the occurrence of cephalosporin-resistant Escherichia coli (E. coli) and vancomycin-resistant enterococci (VRE) and the co-occurrence of antibiotics and mercury in area streams. Fecal indicator bacteria concentrations exceeded the Michigan recreational water-quality standard of 300 E. coli colony forming units (CFU) per 100 milliliters of water in 19 of 35 stream-water samples collected in Oakland County. A gene commonly associated with enterococci from humans was detected in samples from Paint Creek at Rochester and Evans Ditch at Southfield, indicating that human fecal waste is a possible source of fecal contamination at these sites. E. coli resistant to the cephalosporin antibiotics (cefoxitin and/ or ceftriaxone) were found at all sites on at least one occasion. The highest percentages of E. coli isolates resistant to cefoxitin and ceftriaxone were 71 percent (Clinton River at Auburn Hills) and 19 percent (Sashabaw Creek near Drayton Plains), respectively. Cephalosporin-resistant E. coli was detected more frequently in samples from intensively urbanized or industrialized areas than in samples from less urbanized areas. VRE were not detected in any sample collected in this study. Multiple antibiotics (azithromycin, erythromycin, ofloxacin, sulfamethoxazole, and trimethoprim) were detected in water samples from the Clinton River at Auburn Hills, and tylosin (an antibiotic used in veterinary medicine and livestock production that belongs to the macrolide group, along with erythromycin) was detected in one water sample from Paint Creek at Rochester. Concentrations of total mercury were as high as 19.8 nanograms per liter (Evans Ditch at Southfield). There was no relation among percentage of antibiotic-resistant bacteria and measured concentrations of antibiotics or mercury in the water. Genetic elements capable of exchanging multiple antibiotic-resistance

  15. Penicillin's Discovery and Antibiotic Resistance: Lessons for the Future?

    PubMed

    Lobanovska, Mariya; Pilla, Giulia

    2017-03-01

    Undoubtedly, the discovery of penicillin is one of the greatest milestones in modern medicine. 2016 marks the 75th anniversary of the first systemic administration of penicillin in humans, and is therefore an occasion to reflect upon the extraordinary impact that penicillin has had on the lives of millions of people since. This perspective presents a historical account of the discovery of the wonder drug, describes the biological nature of penicillin, and considers lessons that can be learned from the golden era of antibiotic research, which took place between the 1940s and 1960s. Looking back at the history of penicillin might help us to relive this journey to find new treatments and antimicrobial agents. This is particularly relevant today as the emergence of multiple drug resistant bacteria poses a global threat, and joint efforts are needed to combat the rise and spread of resistance.

  16. “Infectious Supercarelessness” in Discussing Antibiotic-Resistant Bacteria

    PubMed Central

    Greenspan, Neil S.

    2017-01-01

    Many bacterial pathogens are exhibiting resistance to increasing numbers of antibiotics making it much more challenging to treat the infections caused by these microbes. In many reports in the media and perhaps even in discussions among physicians and biomedical scientists, these bacteria are frequently referred to as “bugs” with the prefix “super” appended. This terminology has a high potential to elicit unjustified inferences and fails to highlight the broader evolutionary context. Understanding the full range of biological and evolutionary factors that influence the spread and outcomes of infections is critical to formulating effective individual therapies and public health interventions. Therefore, more accurate terminology should be used to refer these multidrug-resistant bacteria. PMID:28174759

  17. A new strategy to fight antimicrobial resistance: the revival of old antibiotics

    PubMed Central

    Cassir, Nadim; Rolain, Jean-Marc; Brouqui, Philippe

    2014-01-01

    The increasing prevalence of hospital and community-acquired infections caused by multidrug-resistant (MDR) bacterial pathogens is limiting the options for effective antibiotic therapy. Moreover, this alarming spread of antimicrobial resistance has not been paralleled by the development of novel antimicrobials. Resistance to the scarce new antibiotics is also emerging. In this context, the rational use of older antibiotics could represent an alternative to the treatment of MDR bacterial pathogens. It would help to optimize the armamentarium of antibiotics in the way to preserve new antibiotics and avoid the prescription of molecules known to favor the spread of resistance (i.e., quinolones). Furthermore, in a global economical perspective, this could represent a useful public health orientation knowing that several of these cheapest “forgotten” antibiotics are not available in many countries. We will review here the successful treatment of MDR bacterial infections with the use of old antibiotics and discuss their place in current practice. PMID:25368610

  18. Transferable Antibiotic Resistances in Marketed Edible Grasshoppers (Locusta migratoria migratorioides).

    PubMed

    Osimani, Andrea; Garofalo, Cristiana; Aquilanti, Lucia; Milanović, Vesna; Cardinali, Federica; Taccari, Manuela; Pasquini, Marina; Tavoletti, Stefano; Clementi, Francesca

    2017-03-24

    Grasshoppers are the most commonly eaten insects by humans worldwide, as they are rich in proteins and micronutrients. This study aimed to assess the occurrence of transferable antibiotic resistance genes in commercialized edible grasshoppers. To this end, the prevalence of 12 selected genes [aac(6')-Ie aph(2″)-Ia, blaZ, erm(A), erm(B), erm(C), mecA, tet(M), tet(O), tet(S), tet(K), vanA, vanB] coding for resistance to antibiotics conventionally used in clinical practice was determined. The majority of samples were positive for tet(M) (70.0%), tet(K) (83.3%) and blaZ (83.3%). A low percentage of samples were positive for erm(B) (16.7%), erm(C) (26.7%), and aac(6')-Ie aph(2″)-Ia (13.3%), whereas no samples were positive for erm(A), vanA, vanB, tet(O), and mecA. Cluster analysis identified 4 main clusters, allowing a separation of samples on the basis of their country of origin.

  19. Prospects for circumventing aminoglycoside kinase mediated antibiotic resistance

    PubMed Central

    Shi, Kun; Caldwell, Shane J.; Fong, Desiree H.; Berghuis, Albert M.

    2013-01-01

    Aminoglycosides are a class of antibiotics with a broad spectrum of antimicrobial activity. Unfortunately, resistance in clinical isolates is pervasive, rendering many aminoglycosides ineffective. The most widely disseminated means of resistance to this class of antibiotics is inactivation of the drug by aminoglycoside-modifying enzymes (AMEs). There are two principal strategies to overcoming the effects of AMEs. The first approach involves the design of novel aminoglycosides that can evade modification. Although this strategy has yielded a number of superior aminoglycoside variants, their efficacy cannot be sustained in the long term. The second approach entails the development of molecules that interfere with the mechanism of AMEs such that the activity of aminoglycosides is preserved. Although such a molecule has yet to enter clinical development, the search for AME inhibitors has been greatly facilitated by the wealth of structural information amassed in recent years. In particular, aminoglycoside phosphotransferases or kinases (APHs) have been studied extensively and crystal structures of a number of APHs with diverse regiospecificity and substrate specificity have been elucidated. In this review, we present a comprehensive overview of the available APH structures and recent progress in APH inhibitor development, with a focus on the structure-guided strategies. PMID:23805415

  20. Rapid identification of antibiotic resistance using droplet microfluidics

    PubMed Central

    Keays, Marie C.; O'Brien, Mark; Hussain, Anam; Kiely, Patrick A.; Dalton, Tara

    2016-01-01

    ABSTRACT Culturing bacteria and monitoring bacterial cell growth is a critical issue when dealing with patients who present with bacterial infections. One of the main challenges that arises is the time taken to identify the particular strain of bacteria and consequently, decide the correct treatment. In the majority of cases, broad spectrum antibiotics are used to target infections when a narrow spectrum drug would be more appropriate. The efficient monitoring of bacterial growth and potential antibiotic resistance is necessary to identify the best treatment options for patients. Minturising the reactions into microfluidic droplets offers a novel method to rapidy analyze bacteria. Microfluidics facilitates low volume reactions that provide a unique system where each droplet reaction acts as an individual bioreactor. Here, we designed and built a novel platform that allowed us to create and monitor E.coli microfluidic droplet cultures. Optical capacity was built in and measurements of bacterial cultures were captured facilitating the continuous monitoring of individual reactions. The capacity of the instrument was demonstrated by the application of treatments to both bacteria and drug resistant strains of bacteria. We were able to detect responses within one hour in the droplet cultures, demonstrating the capacity of this workflow to the culture and rapid characterization of bacterial strains. PMID:26942773

  1. Rapid identification of antibiotic resistance using droplet microfluidics.

    PubMed

    Keays, Marie C; O'Brien, Mark; Hussain, Anam; Kiely, Patrick A; Dalton, Tara

    2016-04-02

    Culturing bacteria and monitoring bacterial cell growth is a critical issue when dealing with patients who present with bacterial infections. One of the main challenges that arises is the time taken to identify the particular strain of bacteria and consequently, decide the correct treatment. In the majority of cases, broad spectrum antibiotics are used to target infections when a narrow spectrum drug would be more appropriate. The efficient monitoring of bacterial growth and potential antibiotic resistance is necessary to identify the best treatment options for patients. Minturising the reactions into microfluidic droplets offers a novel method to rapidy analyze bacteria. Microfluidics facilitates low volume reactions that provide a unique system where each droplet reaction acts as an individual bioreactor. Here, we designed and built a novel platform that allowed us to create and monitor E.coli microfluidic droplet cultures. Optical capacity was built in and measurements of bacterial cultures were captured facilitating the continuous monitoring of individual reactions. The capacity of the instrument was demonstrated by the application of treatments to both bacteria and drug resistant strains of bacteria. We were able to detect responses within one hour in the droplet cultures, demonstrating the capacity of this workflow to the culture and rapid characterization of bacterial strains.

  2. Impact of Manure Fertilization on the Abundance of Antibiotic-Resistant Bacteria and Frequency of Detection of Antibiotic Resistance Genes in Soil and on Vegetables at Harvest

    PubMed Central

    Marti, Romain; Scott, Andrew; Tien, Yuan-Ching; Murray, Roger; Sabourin, Lyne; Zhang, Yun

    2013-01-01

    Consumption of vegetables represents a route of direct human exposure to bacteria found in soil. The present study evaluated the complement of bacteria resistant to various antibiotics on vegetables often eaten raw (tomato, cucumber, pepper, carrot, radish, lettuce) and how this might vary with growth in soil fertilized inorganically or with dairy or swine manure. Vegetables were sown into field plots immediately following fertilization and harvested when of marketable quality. Vegetable and soil samples were evaluated for viable antibiotic-resistant bacteria by plate count on Chromocult medium supplemented with antibiotics at clinical breakpoint concentrations. DNA was extracted from soil and vegetables and evaluated by PCR for the presence of 46 gene targets associated with plasmid incompatibility groups, integrons, or antibiotic resistance genes. Soil receiving manure was enriched in antibiotic-resistant bacteria and various antibiotic resistance determinants. There was no coherent corresponding increase in the abundance of antibiotic-resistant bacteria enumerated from any vegetable grown in manure-fertilized soil. Numerous antibiotic resistance determinants were detected in DNA extracted from vegetables grown in unmanured soil. A smaller number of determinants were additionally detected on vegetables grown only in manured and not in unmanured soil. Overall, consumption of raw vegetables represents a route of human exposure to antibiotic-resistant bacteria and resistance determinants naturally present in soil. However, the detection of some determinants on vegetables grown only in freshly manured soil reinforces the advisability of pretreating manure through composting or other stabilization processes or mandating offset times between manuring and harvesting vegetables for human consumption. PMID:23851089

  3. Impact of manure fertilization on the abundance of antibiotic-resistant bacteria and frequency of detection of antibiotic resistance genes in soil and on vegetables at harvest.

    PubMed

    Marti, Romain; Scott, Andrew; Tien, Yuan-Ching; Murray, Roger; Sabourin, Lyne; Zhang, Yun; Topp, Edward

    2013-09-01

    Consumption of vegetables represents a route of direct human exposure to bacteria found in soil. The present study evaluated the complement of bacteria resistant to various antibiotics on vegetables often eaten raw (tomato, cucumber, pepper, carrot, radish, lettuce) and how this might vary with growth in soil fertilized inorganically or with dairy or swine manure. Vegetables were sown into field plots immediately following fertilization and harvested when of marketable quality. Vegetable and soil samples were evaluated for viable antibiotic-resistant bacteria by plate count on Chromocult medium supplemented with antibiotics at clinical breakpoint concentrations. DNA was extracted from soil and vegetables and evaluated by PCR for the presence of 46 gene targets associated with plasmid incompatibility groups, integrons, or antibiotic resistance genes. Soil receiving manure was enriched in antibiotic-resistant bacteria and various antibiotic resistance determinants. There was no coherent corresponding increase in the abundance of antibiotic-resistant bacteria enumerated from any vegetable grown in manure-fertilized soil. Numerous antibiotic resistance determinants were detected in DNA extracted from vegetables grown in unmanured soil. A smaller number of determinants were additionally detected on vegetables grown only in manured and not in unmanured soil. Overall, consumption of raw vegetables represents a route of human exposure to antibiotic-resistant bacteria and resistance determinants naturally present in soil. However, the detection of some determinants on vegetables grown only in freshly manured soil reinforces the advisability of pretreating manure through composting or other stabilization processes or mandating offset times between manuring and harvesting vegetables for human consumption.

  4. Clusters of antibiotic resistance genes enriched together stay together in swine agriculture

    DOE PAGES

    Johnson, Timothy A.; Stedtfeld, Robert D.; Wang, Qiong; ...

    2016-04-12

    Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundancemore » of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk.Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of resistance

  5. Clusters of antibiotic resistance genes enriched together stay together in swine agriculture

    SciTech Connect

    Johnson, Timothy A.; Stedtfeld, Robert D.; Wang, Qiong; Cole, James R.; Hashsham, Syed A.; Looft, Torey; Zhu, Yong -Guan; Tiedje, James M.

    2016-04-12

    Antibiotic resistance is a worldwide health risk, but the influence of animal agriculture on the genetic context and enrichment of individual antibiotic resistance alleles remains unclear. Using quantitative PCR followed by amplicon sequencing, we quantified and sequenced 44 genes related to antibiotic resistance, mobile genetic elements, and bacterial phylogeny in microbiomes from U.S. laboratory swine and from swine farms from three Chinese regions. We identified highly abundant resistance clusters: groups of resistance and mobile genetic element alleles that cooccur. For example, the abundance of genes conferring resistance to six classes of antibiotics together with class 1 integrase and the abundance of IS6100-type transposons in three Chinese regions are directly correlated. These resistance cluster genes likely colocalize in microbial genomes in the farms. Resistance cluster alleles were dramatically enriched (up to 1 to 10% as abundant as 16S rRNA) and indicate that multidrug-resistant bacteria are likely the norm rather than an exception in these communities. This enrichment largely occurred independently of phylogenetic composition; thus, resistance clusters are likely present in many bacterial taxa. Furthermore, resistance clusters contain resistance genes that confer resistance to antibiotics independently of their particular use on the farms. Selection for these clusters is likely due to the use of only a subset of the broad range of chemicals to which the clusters confer resistance. The scale of animal agriculture and its wastes, the enrichment and horizontal gene transfer potential of the clusters, and the vicinity of large human populations suggest that managing this resistance reservoir is important for minimizing human risk.Agricultural antibiotic use results in clusters of cooccurring resistance genes that together confer resistance to multiple antibiotics. The use of a single antibiotic could select for an entire suite of

  6. Risk factors for antibiotic-resistant E. coli in children in a rural area.

    PubMed

    Seidman, J C; Anitha K, P; Kanungo, R; Bourgeois, A L; Coles, C L

    2009-06-01

    We surveyed antimicrobial susceptibility in faecal Escherichia coli in primary schoolchildren in rural Tamil Nadu, India. Resistance profiles of E. coli samples from local water sources were also obtained. We investigated sociodemographic characteristics as risk factors for resistance and local paediatric prescription patterns. In 119 stool samples, carriage of resistance to 1 antibiotic was 63% and multiple drug resistance was 32%. Resistance outcomes were associated with school of attendance, having a sibling attend the same school, younger age, and less crowded households. Eight of nine water samples were resistant to > or =1 antibiotic. Recent history of medication use was not associated with resistance carriage. Resistance patterns may have been influenced by local paediatric prescription patterns and veterinary antibiotic use. Frequent, low-cost surveillance of commensal resistance can guide development of locally appropriate treatment guidelines. School-based hygiene programmes should be considered as means of limiting the spread of antibiotic resistance.

  7. Temporal Variabilities in Genetic Patterns and Antibiotic Resistance Profiles of Enterococci Isolated from Human Feces

    PubMed Central

    Nishiyama, Masateru; Shimauchi, Hidetaka; Suzuki, Yoshihiro

    2016-01-01

    Temporal variabilities in the genetic patterns and antibiotic resistance profiles of enterococci were monitored over a 7-month period. Enterococcus faecalis isolates (103 strains) collected from feces showed only one genetic pattern and antibiotic resistance profile within 0 d and 30 d. In contrast, after 60 d and 90 d, the genetic patterns and antibiotic resistance profiles of all E. faecalis isolates (8 strains) clearly differed within 30 d. These results indicate that the genetic patterns and antibiotic resistance profiles of E. faecalis in human feces changed to completely dissimilar patterns between 1 and 2 months. PMID:27265342

  8. Relationship between antibiotic- and disinfectant-resistance profiles in bacteria harvested from tap water.

    PubMed

    Khan, Sadia; Beattie, Tara K; Knapp, Charles W

    2016-06-01

    Chlorination is commonly used to control levels of bacteria in drinking water; however, viable bacteria may remain due to chlorine resistance. What is concerning is that surviving bacteria, due to co-selection factors, may also have increased resistance to common antibiotics. This would pose a public health risk as it could link resistant bacteria in the natural environment to human population. Here, we investigated the relationship between chlorine- and antibiotic-resistances by harvesting 148 surviving bacteria from chlorinated drinking-water systems and compared their susceptibilities against chlorine disinfectants and antibiotics. Twenty-two genera were isolated, including members of Paenibacillus, Burkholderia, Escherichia, Sphingomonas and Dermacoccus species. Weak (but significant) correlations were found between chlorine-tolerance and minimum inhibitory concentrations against the antibiotics tetracycline, sulfamethoxazole and amoxicillin, but not against ciprofloxacin; this suggest that chlorine-tolerant bacteria are more likely to also be antibiotic resistant. Further, antibiotic-resistant bacteria survived longer than antibiotic-sensitive organisms when exposed to free chlorine in a contact-time assay; however, there were little differences in susceptibility when exposed to monochloramine. Irrespective of antibiotic-resistance, spore-forming bacteria had higher tolerance against disinfection compounds. The presence of chlorine-resistant bacteria surviving in drinking-water systems may carry additional risk of antibiotic resistance.

  9. Induction of a stable sigma factor SigR by translation-inhibiting antibiotics confers resistance to antibiotics

    PubMed Central

    Yoo, Ji-Sun; Oh, Gyeong-Seok; Ryoo, Sungweon; Roe, Jung-Hye

    2016-01-01

    Antibiotic-producing streptomycetes are rich sources of resistance mechanisms against endogenous and exogenous antibiotics. An ECF sigma factor σR (SigR) is known to govern the thiol-oxidative stress response in Streptomyces coelicolor. Amplification of this response is achieved by producing an unstable isoform of σR called σR′. In this work, we present evidence that antibiotics induce the SigR regulon via a redox-independent pathway, leading to antibiotic resistance. The translation-inhibiting antibiotics enhanced the synthesis of stable σR, eliciting a prolonged response. WblC/WhiB7, a WhiB-like DNA-binding protein, is responsible for inducing sigRp1 transcripts encoding the stable σR. The amount of WblC protein and its binding to the sigRp1 promoter in vivo increased upon antibiotic treatment. A similar phenomenon appears to exist in Mycobacterium tuberculosis as well. These findings reveal a novel antibiotic-induced resistance mechanism conserved among actinomycetes, and also give an explicit example of overlap in cellular damage and defense mechanisms between thiol-oxidative and anti- translational stresses. PMID:27346454

  10. Association between clinical antibiotic resistance and susceptibility of Pseudomonas in the cystic fibrosis lung

    PubMed Central

    Jansen, Gunther; Mahrt, Niels; Tueffers, Leif; Barbosa, Camilo; Harjes, Malte; Adolph, Gernot; Friedrichs, Anette; Krenz-Weinreich, Annegret; Rosenstiel, Philip; Schulenburg, Hinrich

    2016-01-01

    Background and objectives: Cystic fibrosis patients suffer from chronic lung infections that require long-term antibiotic therapy. Pseudomonas readily evolve resistance, rendering antibiotics ineffective. In vitro experiments suggest that resistant bacteria may be treated by exploiting their collateral sensitivity to other antibiotics. Here, we investigate correlations of sensitivity and resistance profiles of Pseudomonas aeruginosa that naturally adapted to antibiotics in the cystic fibrosis lung. Methodology: Resistance profiles for 13 antibiotics were obtained using broth dilution, E-test and VITEK mass spectroscopy. Genetic variants were determined from whole-genome sequences and interrelationships among isolates were analyzed using 13 MLST loci. Result: Our study focused on 45 isolates from 13 patients under documented treatment with antibiotics. Forty percent of these were clinically resistant and 15% multi-drug resistant. Colistin resistance was found once, despite continuous colistin treatment and even though colistin resistance can readily evolve experimentally in the laboratory. Patients typically harbored multiple genetically and phenotypically distinct clones. However, genetically similar clones often had dissimilar resistance profiles. Isolates showed mutations in genes encoding cell wall synthesis, alginate production, efflux pumps and antibiotic modifying enzymes. Cross-resistance was commonly observed within antibiotic classes and between aminoglycosides and β-lactam antibiotics. No evidence was found for consistent phenotypic resistance to one antibiotic and sensitivity to another within one genotype. Conclusions and implications: Evidence supporting potential collateral sensitivity in clinical P. aeruginosa isolates remains equivocal. However, cross-resistance within antibiotic classes is common. Colistin therapy is promising since resistance to it was rare despite its intensive use in the studied patients. PMID:27193199

  11. FECAL SOURCE TRACKING BY ANTIBIOTIC RESISTANCE ANALYSIS ON A WATERSHED EXHIBITING LOW RESISTANCE

    EPA Science Inventory

    The ongoing development of microbial source tracking has made it possible to identify contamination sources with varying accuracy, depending on the method used. The purpose of this study was done to test the efficiency of the antibiotic resistance analysis (ARA) method under low ...

  12. Acquired antibiotic resistance among wild animals: the case of Iberian Lynx (Lynx pardinus).

    PubMed

    Sousa, Margarida; Gonçalves, Alexandre; Silva, Nuno; Serra, Rodrigo; Alcaide, Eva; Zorrilla, Irene; Torres, Carmen; Caniça, Manuela; Igrejas, Gilberto; Poeta, Patrícia

    2014-01-01

    The selective pressure generated by the clinical misuse of antibiotics has been the major driving force leading to the emergence of antibiotic resistance among bacteria. Antibiotics or even resistant bacteria are released into the environment and contaminate the surrounding areas. Human and animal populations in contact with these sources are able to become reservoirs of these resistant organisms. Then, due to the convergence between habitats, the contact of wild animals with other animals, humans, or human sources is now more common and this leads to an increase in the exchange of resistance determinants between their microbiota. Indeed, it seems that wildlife populations living in closer proximity to humans have higher levels of antibiotic resistance. Now, the Iberian Lynx (Lynx pardinus) is a part of this issue, being suggested as natural reservoir of acquired resistant bacteria. The emerging public health concern regarding microbial resistance to antibiotics is becoming true: the bacteria are evolving and are now affecting unintentional hosts.

  13. Ribosomal mutations promote the evolution of antibiotic resistance in a multidrug environment.

    PubMed

    Gomez, James E; Kaufmann-Malaga, Benjamin B; Wivagg, Carl N; Kim, Peter B; Silvis, Melanie R; Renedo, Nikolai; Ioerger, Thomas R; Ahmad, Rushdy; Livny, Jonathan; Fishbein, Skye; Sacchettini, James C; Carr, Steven A; Hung, Deborah T

    2017-02-21

    Antibiotic resistance arising via chromosomal mutations is typically specific to a particular antibiotic or class of antibiotics. We have identified mutations in genes encoding ribosomal components in Mycobacterium smegmatis that confer resistance to several structurally and mechanistically unrelated classes of antibiotics and enhance survival following heat shock and membrane stress. These mutations affect ribosome assembly and cause large-scale transcriptomic and proteomic changes, including the downregulation of the catalase KatG, an activating enzyme required for isoniazid sensitivity, and upregulation of WhiB7, a transcription factor involved in innate antibiotic resistance. Importantly, while these ribosomal mutations have a fitness cost in antibiotic-free medium, in a multidrug environment they promote the evolution of high-level, target-based resistance. Further, suppressor mutations can then be easily acquired to restore wild-type growth. Thus, ribosomal mutations can serve as stepping-stones in an evolutionary path leading to the emergence of high-level, multidrug resistance.

  14. Antibiotic resistance patterns of major zoonotic pathogens from all-natural, antibiotic-free, pasture-raised broiler flocks in the southeastern United States

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of antibiotics in agroecosystems has been implicated in the rise in antibiotic resistance that can affect environmental, animal, and human health. In order to effectively determine the environmental impact of antibiotic use in agroecosystems, appropriate background levels of antibiotic resi...

  15. Antibiotic Restriction Might Facilitate the Emergence of Multi-drug Resistance.

    PubMed

    Obolski, Uri; Stein, Gideon Y; Hadany, Lilach

    2015-06-01

    High antibiotic resistance frequencies have become a major public health issue. The decrease in new antibiotics' production, combined with increasing frequencies of multi-drug resistant (MDR) bacteria, cause substantial limitations in treatment options for some bacterial infections. To diminish overall resistance, and especially the occurrence of bacteria that are resistant to all antibiotics, certain drugs are deliberately scarcely used--mainly when other options are exhausted. We use a mathematical model to explore the efficiency of such antibiotic restrictions. We assume two commonly used drugs and one restricted drug. The model is examined for the mixing strategy of antibiotic prescription, in which one of the drugs is randomly assigned to each incoming patient. Data obtained from Rabin medical center, Israel, is used to estimate realistic single and double antibiotic resistance frequencies in incoming patients. We find that broad usage of the hitherto restricted drug can reduce the number of incorrectly treated patients, and reduce the spread of bacteria resistant to both common antibiotics. Such double resistant infections are often eventually treated with the restricted drug, and therefore are prone to become resistant to all three antibiotics. Thus, counterintuitively, a broader usage of a formerly restricted drug can sometimes lead to a decrease in the emergence of bacteria resistant to all drugs. We recommend re-examining restriction of specific drugs, when multiple resistance to the relevant alternative drugs already exists.

  16. Insects Represent a Link between Food Animal Farms and the Urban Environment for Antibiotic Resistance Traits

    PubMed Central

    Ghosh, Anuradha

    2014-01-01

    Antibiotic-resistant bacterial infections result in higher patient mortality rates, prolonged hospitalizations, and increased health care costs. Extensive use of antibiotics as growth promoters in the animal industry represents great pressure for evolution and selection of antibiotic-resistant bacteria on farms. Despite growing evidence showing that antibiotic use and bacterial resistance in food animals correlate with resistance in human pathogens, the proof for direct transmission of antibiotic resistance is difficult to provide. In this review, we make a case that insects commonly associated with food animals likely represent a direct and important link between animal farms and urban communities for antibiotic resistance traits. Houseflies and cockroaches have been shown to carry multidrug-resistant clonal lineages of bacteria identical to those found in animal manure. Furthermore, several studies have demonstrated proliferation of bacteria and horizontal transfer of resistance genes in the insect digestive tract as well as transmission of resistant bacteria by insects to new substrates. We propose that insect management should be an integral part of pre- and postharvest food safety strategies to minimize spread of zoonotic pathogens and antibiotic resistance traits from animal farms. Furthermore, the insect link between the agricultural and urban environment presents an additional argument for adopting prudent use of antibiotics in the food animal industry. PMID:24705326

  17. Effects of antibiotic resistance alleles on bacterial evolutionary responses to viral parasites.

    PubMed

    Arias-Sánchez, Flor I; Hall, Alex R

    2016-05-01

    Antibiotic resistance has wide-ranging effects on bacterial phenotypes and evolution. However, the influence of antibiotic resistance on bacterial responses to parasitic viruses remains unclear, despite the ubiquity of such viruses in nature and current interest in therapeutic applications. We experimentally investigated this by exposing various Escherichia coli genotypes, including eight antibiotic-resistant genotypes and a mutator, to different viruses (lytic bacteriophages). Across 960 populations, we measured changes in population density and sensitivity to viruses, and tested whether variation among bacterial genotypes was explained by their relative growth in the absence of parasites, or mutation rate towards phage resistance measured by fluctuation tests for each phage. We found that antibiotic resistance had relatively weak effects on adaptation to phages, although some antibiotic-resistance alleles impeded the evolution of resistance to phages via growth costs. By contrast, a mutator allele, often found in antibiotic-resistant lineages in pathogenic populations, had a relatively large positive effect on phage-resistance evolution and population density under parasitism. This suggests costs of antibiotic resistance may modify the outcome of phage therapy against pathogenic populations previously exposed to antibiotics, but the effects of any co-occurring mutator alleles are likely to be stronger.

  18. Insects represent a link between food animal farms and the urban environment for antibiotic resistance traits.

    PubMed

    Zurek, Ludek; Ghosh, Anuradha

    2014-06-01

    Antibiotic-resistant bacterial infections result in higher patient mortality rates, prolonged hospitalizations, and increased health care costs. Extensive use of antibiotics as growth promoters in the animal industry represents great pressure for evolution and selection of antibiotic-resistant bacteria on farms. Despite growing evidence showing that antibiotic use and bacterial resistance in food animals correlate with resistance in human pathogens, the proof for direct transmission of antibiotic resistance is difficult to provide. In this review, we make a case that insects commonly associated with food animals likely represent a direct and important link between animal farms and urban communities for antibiotic resistance traits. Houseflies and cockroaches have been shown to carry multidrug-resistant clonal lineages of bacteria identical to those found in animal manure. Furthermore, several studies have demonstrated proliferation of bacteria and horizontal transfer of resistance genes in the insect digestive tract as well as transmission of resistant bacteria by insects to new substrates. We propose that insect management should be an integral part of pre- and postharvest food safety strategies to minimize spread of zoonotic pathogens and antibiotic resistance traits from animal farms. Furthermore, the insect link between the agricultural and urban environment presents an additional argument for adopting prudent use of antibiotics in the food animal industry.

  19. Trends in antibiotic resistance of respiratory pathogens: an analysis and commentary on a collaborative surveillance study.

    PubMed

    Baquero, F

    1996-07-01

    The evolution of antibiotic resistance was studied among common respiratory tract pathogens in five countries of the European Union and in the USA during 1992-1993. The data obtained from a collaborative surveillance study were submitted to population analysis, to detect possible shifts in antibiotic susceptibility and, therefore, associated mechanisms of resistance. Among the emerging haemophilus influenzae phenotypes were isolates that did not correspond to the beta-lactamase negative, amino-penicillin resistant (BLNAR) phenotype, but were beta-lactamase producers showing low level ceftriaxone resistance (early extended spectrum beta-lactamases?) amoxycillin susceptible strains with low level ceftriaxone resistance (PBP modification?) and isolates with high-level fluoroquinolone resistance. Moraxella catarrhalis resistance to ceftriaxone erythromycin or fluoroquinolones was noted. The quantitative evolution of antibiotic resistance may reach saturation in some countries with a very high proportion of resistant strains, for example, Spain and France. Qualitatively, resistant strains may be selected that have broader or more effective mechanisms of resistance, particularly under the recently introduced pressure of more active antibiotics of the same family. In countries with modest levels of antibiotic resistance (UK, Germany, Italy), attention should be paid to the misuse of antibiotics with a propensity to select low-level resistant strains. In this respect, the relative prescribing of aminopenicillins and oral cephalosporins in the UK (a high ratio and low prevalence of Streptococcus pneumoniae) and resistance to penicillin in the USA (a low ratio and high prevalence of resistance) is of potential importance.

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

    PubMed

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

    2017-02-09

    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.

  1. Antibiotic usage in animals: impact on bacterial resistance and public health.

    PubMed

    van den Bogaard, A E; Stobberingh, E E

    1999-10-01

    Antibiotic use whether for therapy or prevention of bacterial diseases, or as performance enhancers will result in antibiotic resistant micro-organisms, not only among pathogens but also among bacteria of the endogenous microflora of animals. The extent to which antibiotic use in animals will contribute to the antibiotic resistance in humans is still under much debate. In addition to the veterinary use of antibiotics, the use of these agents as antimicrobial growth promoters (AGP) greatly influences the prevalence of resistance in animal bacteria and a poses risk factor for the emergence of antibiotic resistance in human pathogens. Antibiotic resistant bacteria such as Escherichia coli, Salmonella spp., Campylobacter spp. and enterococci from animals can colonise or infect the human population via contact (occupational exposure) or via the food chain. Moreover, resistance genes can be transferred from bacteria of animals to human pathogens in the intestinal flora of humans. In humans, the control of resistance is based on hygienic measures: prevention of cross contamination and a decrease in the usage of antibiotics. In food animals housed closely together, hygienic measures, such as prevention of oral-faecal contact, are not feasible. Therefore, diminishing the need for antibiotics is the only possible way of controlling resistance in large groups of animals. This can be achieved by improvement of animal husbandry systems, feed composition and eradication of or vaccination against infectious diseases. Moreover, abolishing the use of antibiotics as feed additives for growth promotion in animals bred as a food source for humans would decrease the use of antibiotics in animals on a worldwide scale by nearly 50%. This would not only diminish the public health risk of dissemination of resistant bacteria or resistant genes from animals to humans, but would also be of major importance in maintaining the efficacy of antibiotics in veterinary medicine.

  2. Increase in Antibiotic-Resistant Gram-Negative Bacterial Infections in Febrile Neutropenic Children

    PubMed Central

    2016-01-01

    Background The incidence of bacteremia caused by Gram-negative bacteria has increased recently in febrile neutropenic patients with the increase of antibiotic-resistant Gram-negative bacterial infections. This study aimed to identify the distribution of causative bacteria and the proportion of antibiotic-resistant bacteria in bacteremia diagnosed in febrile neutropenic children. Materials and Methods The medical records of febrile neutropenic children diagnosed with bacteremia between 2010 and 2014 were retrospectively reviewed. The causative bacteria and proportion of antibiotic-resistant bacteria were investigated and compared yearly during the study period. The clinical impact of antibiotic-resistant bacterial infections was also determined. Results A total of 336 bacteremia episodes were identified. During the entire study period, 181 (53.9%) and 155 (46.1%) episodes were caused by Gram-negative and Gram-positive bacteria, respectively. Viridans streptococci (25.9%), Klebsiella spp. (16.7%), and Escherichia coli (16.4%) were the most frequent causative bacteria. The overall distribution of causative bacteria was not significantly different annually. Antibiotic-resistant bacteria were identified in 85 (25.3%) episodes, and the proportion of antibiotic-resistant bacteria was not significantly different annually. Extended-spectrum β-lactamase-producing E. coli and Klebsiella spp. were most common among antibiotic-resistant Gram-negative bacteria, and they accounted for 30.6% (n = 34) of the identified E. coli and K. pneumoniae. Methicillin-resistant coagulase-negative staphylococci were most common among antibiotic-resistant Gram-positive bacteria, and it accounted for 88.5% (n = 23) of the identified coagulase-negative staphylococci. Antibiotic-resistant bacterial infections, especially antibiotic-resistant Gram-negative bacterial infections, caused significantly higher mortality due to bacteremia compared with non-antibiotic-resistant bacterial infections (P <0

  3. Evaluating the mobility potential of antibiotic resistance genes in environmental resistomes without metagenomics

    PubMed Central

    Pärnänen, Katariina; Karkman, Antti; Tamminen, Manu; Lyra, Christina; Hultman, Jenni; Paulin, Lars; Virta, Marko

    2016-01-01

    Antibiotic resistance genes are ubiquitous in the environment. However, only a fraction of them are mobile and able to spread to pathogenic bacteria. Until now, studying the mobility of antibiotic resistance genes in environmental resistomes has been challenging due to inadequate sensitivity and difficulties in contig assembly of metagenome based methods. We developed a new cost and labor efficient method based on Inverse PCR and long read sequencing for studying mobility potential of environmental resistance genes. We applied Inverse PCR on sediment samples and identified 79 different MGE clusters associated with the studied resistance genes, including novel mobile genetic elements, co-selected resistance genes and a new putative antibiotic resistance gene. The results show that the method can be used in antibiotic resistance early warning systems. In comparison to metagenomics, Inverse PCR was markedly more sensitive and provided more data on resistance gene mobility and co-selected resistances. PMID:27767072

  4. The path of least resistance: paying for antibiotics in non-human uses.

    PubMed

    Hollis, Aidan; Ahmed, Ziana

    2014-11-01

    Antibiotic resistance is a critical threat to human and animal health. Despite the importance of antibiotics, regulators continue to allow antibiotics to be used in low-value applications--subtherapeutic dosing in animals, and spraying tobacco plants for blue mold, for example--where the benefits are unlikely to outweigh the costs in terms of increased resistance. We explore the application of a user fee in non-human uses of antibiotics. Such a fee would efficiently deter low value uses while also providing funding to support the development of the urgently needed new antibiotics.

  5. AdeIJK, a Resistance-Nodulation-Cell Division Pump Effluxing Multiple Antibiotics in Acinetobacter baumannii▿

    PubMed Central

    Damier-Piolle, Laurence; Magnet, Sophie; Brémont, Sylvie; Lambert, Thierry; Courvalin, Patrice

    2008-01-01

    We have identified a second resistance-nodulation-cell division (RND)-type efflux pump, AdeIJK, in clinical isolate Acinetobacter baumannii BM4454. The adeI, adeJ, and adeK genes encode, respectively, the membrane fusion, RND, and outer membrane components of the pump. AdeJ belongs to the AcrB protein family (57% identity with AcrB from Escherichia coli). mRNA analysis by Northern blotting and reverse transcription-PCR indicated that the genes were cotranscribed. Overexpression of the cloned adeIJK operon was toxic in both E. coli and Acinetobacter. The adeIJK genes were detected in all of the 60 strains of A. baumannii tested. The two latter observations suggest that the AdeIJK complex might contribute to intrinsic but not to acquired antibiotic resistance in Acinetobacter. To characterize the substrate specificity of the pump, we have constructed derivatives of BM4454 in which adeIJK (strain BM4579), adeABC (strain BM4561), or both groups of genes (strain BM4652) were inactivated by deletion-insertion. Determination of the antibiotic susceptibility of these strains and of BM4652 and BM4579, in which the adeIJK operon was provided in trans, indicated that the AdeIJK pump contributes to resistance to β-lactams, chloramphenicol, tetracycline, erythromycin, lincosamides, fluoroquinolones, fusidic acid, novobiocin, rifampin, trimethoprim, acridine, safranin, pyronine, and sodium dodecyl sulfate. The chemical structure of these molecules suggests that amphiphilic compounds are the preferred substrates. The AdeABC and AdeIJK efflux systems contributed in a more than additive fashion to tigecycline resistance. PMID:18086852

  6. Occurrence and distribution of antibiotics, antibiotic resistance genes in the urban rivers in Beijing, China.

    PubMed

    Xu, Yan; Guo, Changsheng; Luo, Yi; Lv, Jiapei; Zhang, Yuan; Lin, Haixia; Wang, Li; Xu, Jian

    2016-06-01

    The occurrence and distribution of sulfonamide and tetracycline, corresponding bacterial resistant rate and resistance genes (ARGs) and two integrase genes were investigated in seven urban rivers in Beijing, China. The total concentration of sulfonamide and tetracycline ranged from 1.3 × 10(1)-1.5 × 10(3) ng/L and 3.9 × 10(1)-5.4 × 10(4) ng/L for water, and 1.0 × 10(0)-2.7 × 10(2) and 3.1 × 10(1)-1.6 × 10(2) ng/g for sediment, respectively. The sul resistant rate was 2-3 times higher than tet resistant rate in both surface water and sediment. The average rate of sul resistance and tet resistance were up to 81.3% and 38.6% in surface water, 89.1% and 69.4% in the sediment, respectively. The sul1, tetA and tetE genes were predominant in term of the absolute abundance. The absolute abundance of ARGs in Wenyu River and Qinghe River, which were close to the direct discharging sites, were 5-50 times higher than those in the other investigated urban rivers, suggesting that the source release played an important role in the distribution of ARGs. The sul1 and sul2 genes had positive correlation (p < 0.05) with sulfonamides, and the tet resistance genes was significantly correlated with tetracyclines (p < 0.05), indicating that some ARGs and antibiotics in the urban rivers had identical sources of pollution. Considering principal component analysis, sampling sites (QH5, QH6, B1, B2, B3 and BX2) intimated that a complex interplay of processes govern fate and transport of ARGs in the junction of rivers. These results are significant to understand the fate, and the contribution of ARGs from the source release. In view of the large-scale investigation of urban rivers system in Beijing, it reflected the bacterial resistance in sewage drainage system. Such investigation highlights the management on controlling the pollutant release which was seemed as a major driving force for the maintenance and propagation of many ARGs during the development of

  7. Intrinsic and induced drug resistance mechanisms: in silico investigations at the cellular and tissue scales.

    PubMed

    Liu, Cong; Krishnan, J; Xu, Xiao Yun

    2015-09-01

    Multiple cellular drug resistance mechanisms are present in a broad range of tumour types and act to counteract the effects of drugs. There are independent mechanisms by which drug resistance occurs; these include (i) the multi-drug resistance mechanism involving upregulation of ABC transporter proteins and (ii) intracellular mechanisms which sequester/degrade/detoxify drugs. In addition, drug resistance mechanisms could be either intrinsic, or directly induced by the drug. In this paper we focus on the behaviour of intrinsic and induced variants of these resistance mechanisms in solid tumours, by systematically elucidating their cellular and tissue level effects with an aim to bridge the gap between cell and tissue levels. This is achieved in a controlled in silico setting, which allows for an investigation of the interplay between transport, resistance pathways, and tissue level effects. Overall the paper (i) provides insights into the tissue level functioning of widespread classes of intracellular resistance mechanisms, showing important differences, (ii) systematically elucidates the difference between intrinsic and induced drug resistance mechanisms at the cell and tissue levels, (iii) demonstrates how spatial heterogeneity in intrinsic resistance in cells can significantly affect the response of solid tumours to drugs, and (iv) examines how different independent resistance mechanisms work in concert, to counteract drug dosages in tumours.

  8. Evidence of Increased Antibiotic Resistance in Phylogenetically-Diverse Aeromonas Isolates from Semi-Intensive Fish Ponds Treated with Antibiotics

    PubMed Central

    Patil, Hemant J.; Benet-Perelberg, Ayana; Naor, Alon; Smirnov, Margarita; Ofek, Tamir; Nasser, Ahmed; Minz, Dror; Cytryn, Eddie

    2016-01-01

    The genus Aeromonas is ubiquitous in aquatic environments encompassing a broad range of fish and human pathogens. Aeromonas strains are known for their enhanced capacity to acquire and exchange antibiotic resistance genes and therefore, are frequently targeted as indicator bacteria for monitoring antimicrobial resistance in aquatic environments. This study evaluated temporal trends in Aeromonas diversity and antibiotic resistance in two adjacent semi-intensive aquaculture facilities to ascertain the effects of antibiotic treatment on antimicrobial resistance. In the first facility, sulfadiazine-trimethoprim was added prophylactically to fingerling stocks and water column-associated Aeromonas were monitored periodically over an 11-month fish fattening cycle to assess temporal dynamics in taxonomy and antibiotic resistance. In the second facility, Aeromonas were isolated from fish skin ulcers sampled over a 3-year period and from pond water samples to assess associations between pathogenic strains to those in the water column. A total of 1200 Aeromonas isolates were initially screened for sulfadiazine resistance and further screened against five additional antimicrobials. In both facilities, strong correlations were observed between sulfadiazine resistance and trimethoprim and tetracycline resistances, whereas correlations between sulfadiazine resistance and ceftriaxone, gentamicin, and chloramphenicol resistances were low. Multidrug resistant strains as well as sul1, tetA, and intI1 gene-harboring strains were significantly higher in profiles sampled during the fish cycle than those isolated prior to stocking and these genes were extremely abundant in the pathogenic strains. Five phylogenetically distinct Aeromonas clusters were identified using partial rpoD gene sequence analysis. Interestingly, prior to fingerling stocking the diversity of water column strains was high, and representatives from all five clusters were identified, including an A. salmonicida cluster

  9. Survival of Antibiotic Resistant Bacteria and Horizontal Gene Transfer Control Antibiotic Resistance Gene Content in Anaerobic Digesters

    PubMed Central

    Miller, Jennifer H.; Novak, John T.; Knocke, William R.; Pruden, Amy

    2016-01-01

    Understanding fate of antibiotic resistant bacteria (ARB) vs. their antibiotic resistance genes (ARGs) during wastewater sludge treatment is critical in order to reduce the spread of antibiotic resistance through process optimization. Here, we spiked high concentrations of tetracycline-resistant bacteria, isolated from mesophilic (Iso M1-1—a Pseudomonas sp.) and thermophilic (Iso T10—a Bacillus sp.) anaerobic digested sludge, into batch digesters and monitored their fate by plate counts and quantitative polymerase chain reaction (QPCR) of their corresponding tetracycline ARGs. In batch studies, spiked ARB plate counts returned to baseline (thermophilic) or 1-log above baseline (mesophilic) while levels of the ARG present in the spiked isolate [tet(G)] remained high in mesophilic batch reactors. To compare results under semi-continuous flow conditions with natural influent variation, tet(O), tet(W), and sul1 ARGs, along with the intI1 integrase gene, were monitored over a 9-month period in the raw feed sludge and effluent sludge of lab-scale thermophilic and mesophilic anaerobic digesters. sul1 and intI1 in mesophilic and thermophilic digesters correlated positively (Spearman rho = 0.457–0.829, P < 0.05) with the raw feed sludge. There was no correlation in tet(O) or tet(W) ratios in raw sludge and mesophilic digested sludge or thermophilic digested sludge (Spearman rho = 0.130–0.486, P = 0.075–0.612). However, in the thermophilic digester, the tet(O) and tet(W) ratios remained consistently low over the entire monitoring period. We conclude that the influent sludge microbial composition can influence the ARG content of a digester, apparently as a result of differential survival or death of ARBs or horizontal gene transfer of genes between raw sludge ARBs and the digester microbial community. Notably, mesophilic digestion was more susceptible to ARG intrusion than thermophilic digestion, which may be attributed to a higher rate of ARB survival and

  10. Insertion sequence IS256 in canine pyoderma isolates of Staphylococcus pseudintermedius associated with antibiotic resistance.

    PubMed

    Casagrande Proietti, P; Bietta, A; Coletti, M; Marenzoni, M L; Scorza, A V; Passamonti, F

    2012-06-15

    Staphylococcus pseudintermedius is the most frequent staphylococcal species isolated from canine pyoderma. The control of S. pseudintermedius infection is often difficult due to the expanded antimicrobial resistance phenotypes. Antibiotic resistance in staphylococcal pathogens is often associated to mobile genetic elements such as the insertion sequence IS256 that was first described as a part of the transposon Tn4001, which confers aminoglycoside resistance in Staphylococcus aureus and in Staphylococcus epidermidis. In this study a collection of 70 S. pseudintermedius isolates from canine pyoderma was used to investigate antimicrobial susceptibility to 15 antibiotics and the presence of IS256, not revealed in S. pseudintermedius yet. Antibiotic resistance profiling demonstrated that all S. pseudintermedius isolates had a multi-drug resistance phenotype, exhibiting simultaneous resistance to at least five antibiotics; indeed methicillin resistant S. pseudintermedius isolates were simultaneously resistant to at least nine antibiotics and all were also gentamicin resistant. PCR analyses revealed the presence of IS256 in 43/70 S. pseudintemedius isolates. The association between the presence of IS256 and the resistance was particularly significant for certain antibiotics: cefovecin, amikacin, gentamicin and oxacillin (χ(2)p-value<0.05). However, there was a striking result in frequency of strains resistant to gentamicin and oxacillin, suggesting a specific association between the presence of the IS256 element and the determinants for the resistance to these antibiotics. To the best of our knowledge, this is the first report showing the detection of IS256 in S. pseudintermedius isolates and its association with antibiotic resistance. Our findings suggest that S. pseudintermedius may acquire antibiotic resistance genes through mobile genetic elements which may play a predominant role in the dissemination of multi-drug resistance.

  11. Strength of Selection Pressure Is an Important Parameter Contributing to the Complexity of Antibiotic Resistance Evolution

    PubMed Central

    Oz, Tugce; Guvenek, Aysegul; Yildiz, Sadik; Karaboga, Enes; Tamer, Yusuf Talha; Mumcuyan, Nirva; Ozan, Vedat Burak; Senturk, Gizem Hazal; Cokol, Murat; Yeh, Pamela; Toprak, Erdal

    2014-01-01

    Revealing the genetic changes responsible for antibiotic resistance can be critical for developing novel antibiotic therapies. However, systematic studies correlating genotype to phenotype in the context of antibiotic resistance have been missing. In order to fill in this gap, we evolved 88 isogenic Escherichia coli populations against 22 antibiotics for 3 weeks. For every drug, two populations were evolved under strong selection and two populations were evolved under mild selection. By quantifying evolved populations’ resistances against all 22 drugs, we constructed two separate cross-resistance networks for strongly and mildly selected populations. Subsequently, we sequenced representative colonies isolated from evolved populations for revealing the genetic basis for novel phenotypes. Bacterial populations that evolved resistance against antibiotics under strong selection acquired high levels of cross-resistance against several antibiotics, whereas other bacterial populations evolved under milder selection acquired relatively weaker cross-resistance. In addition, we found that strongly selected strains against aminoglycosides became more susceptible to five other drug classes compared with their wild-type ancestor as a result of a point mutation on TrkH, an ion transporter protein. Our findings suggest that selection strength is an important parameter contributing to the complexity of antibiotic resistance problem and use of high doses of antibiotics to clear infections has the potential to promote increase of cross-resistance in clinics. PMID:24962091

  12. The transport of antibiotic resistance genes and residues in groundwater near swine production facilities

    NASA Astrophysics Data System (ADS)

    Lin, Y. F.; Yannarell, A. C.; Mackie, R. I.; Krapac, I. G.; Chee-Sanford, J. S.; Koike, S.

    2008-12-01

    The use of antibiotics at concentrated animal feeding operations (CAFOs) for disease prevention, disease treatment, and growth promotion can contribute to the spread of antibiotic compounds, their breakdown products, and antibiotic resistant bacteria and/or the genes that confer resistance. In addition, constitutive use of antibiotics at sub-therapeutic levels can select for antibiotic resistance among the bacteria that inhabit animal intestinal tracts, onsite manure treatment facilities, and any environments receiving significant inputs of manure (e.g. through waste lagoon leakage or fertilizer amendments to farm soils). If the antibiotic resistant organisms persist in these new environments, or if they participate in genetic exchanges with the native microflora, then CAFOs may constitute a significant reservoir for the spread of antibiotic resistance to the environment at large. Our results have demonstrated that leakage from waste treatment lagoons can influence the presence and persistence of tetracycline resistance genes in the shallow aquifer adjacent to swine CAFOs, and molecular phylogeny allowed us to distinguish "native" tetracycline resistance genes in control groundwater wells from manure-associated genes introduced from the lagoon. We have also been able to detect the presence of erythromycin resistance genes in CAFO surface and groundwater even though erythromycin is strictly reserved for use in humans and thus is not utilized at any of these sites. Ongoing research, including modeling of particle transport in groundwater, will help to determine the potential spatial and temporal extent of CAFO-derived antibiotic resistance.

  13. Induction of human plasmablasts during infection with antibiotic-resistant nosocomial bacteria

    PubMed Central

    Band, Victor I.; Ibegbu, Chris; Kaur, Surinder Pal; Cagle, Stephanie M.; Trible, Ronald; Jones, Crystal L.; Wang, Yun F.; Kraft, Colleen S.; Ray, Susan M.; Wrammert, Jens; Weiss, David S.

    2014-01-01

    Objectives Nosocomial pathogens such as Acinetobacter baumannii are a growing public health threat, due in part to their increasing resistance to antibiotics. Since some strains are resistant to all available antibiotics, novel therapies are urgently needed. Plasmablasts are short-lived B cells found in the blood that can be collected and harnessed to produce therapeutic antibodies. We set out to determine whether plasmablasts are induced during infection with A. baumannii and other nosocomial pathogens. Methods We obtained blood samples from patients infected with antibiotic-resistant nosocomial pathogens, and analysed their plasmablast response by flow cytometry. Results We observed a strong induction of plasmablasts in patients with antibiotic-resistant A. baumannii infection. Furthermore, plasmablasts were also induced in response to other drug-resistant nosocomial pathogens. Conclusions These data suggest that plasmablasts may be broadly harnessed to develop therapeutic antibodies to combat otherwise untreatable antibiotic-resistant infections. PMID:24583361

  14. Novel antibiotic regimens against Enterococcus faecium resistant to ampicillin, vancomycin, and gentamicin.

    PubMed Central

    Landman, D; Mobarakai, N K; Quale, J M

    1993-01-01

    Enterococci have emerged as significant nosocomial pathogens. Enterococci with resistance to commonly used antibiotics are appearing more frequently. We encountered at our institution several infections caused by Enterococcus faecium with high-level resistance to ampicillin, vancomycin, and gentamicin. The optimal antibiotic therapy for serious infections with unusually resistant enterococci has not been established. Using time-kill studies, we tested the effectiveness of various antibiotic combinations against 15 isolates of multidrug-resistant enterococci. No antibiotic was consistently effective when used alone. The combination of ampicillin plus ciprofloxacin was bactericidal for the 12 isolates for which the ciprofloxacin MIC was < or = 8 micrograms/ml. The combination of ciprofloxacin plus novobiocin also demonstrated activity against these isolates. No combination was found to be bactericidal for the remaining three isolates, which were highly ciprofloxacin resistant. These antibiotic combinations may be important for the future treatment of serious infections caused by these resistant pathogens. PMID:8239604

  15. Elucidating selection processes for antibiotic resistance in sewage treatment plants using metagenomics.

    PubMed

    Bengtsson-Palme, Johan; Hammarén, Rickard; Pal, Chandan; Östman, Marcus; Björlenius, Berndt; Flach, Carl-Fredrik; Fick, Jerker; Kristiansson, Erik; Tysklind, Mats; Larsson, D G Joakim

    2016-12-01

    Sewage treatment plants (STPs) have repeatedly been suggested as "hotspots" for the emergence and dissemination of antibiotic-resistant bacteria. A critical question still unanswered is if selection pressures within STPs, caused by residual antibiotics or other co-selective agents, are sufficient to specifically promote resistance. To address this, we employed shotgun metagenomic sequencing of samples from different steps of the treatment process in three Swedish STPs. In parallel, concentrations of selected antibiotics, biocides and metals were analyzed. We found that concentrations of tetracycline and ciprofloxacin in the influent were above predicted concentrations for resistance selection, however, there was no consistent enrichment of resistance genes to any particular class of antibiotics in the STPs, neither for biocide and metal resistance genes. The most substantial change of the bacterial communities compared to human feces occurred already in the sewage pipes, manifested by a strong shift from obligate to facultative anaerobes. Through the treatment process, resistance genes against antibiotics, biocides and metals were not reduced to the same extent as fecal bacteria. The OXA-48 gene was consistently enriched in surplus and digested sludge. We find this worrying as OXA-48, still rare in Swedish clinical isolates, provides resistance to carbapenems, one of our most critically important classes of antibiotics. Taken together, metagenomics analyses did not provide clear support for specific antibiotic resistance selection. However, stronger selective forces affecting gross taxonomic composition, and with that resistance gene abundances, limit interpretability. Comprehensive analyses of resistant/non-resistant strains within relevant species are therefore warranted.

  16. Antibiotic resistance among cultured bacterial isolates from bioethanol fermentation facilities across the United States.

    PubMed

    Murphree, Colin A; Heist, E Patrick; Moe, Luke A

    2014-09-01

    Bacterial contamination of fuel ethanol fermentations by lactic acid bacteria (LAB) can have crippling effects on bioethanol production. Producers have had success controlling bacterial growth through prophylactic addition of antibiotics to fermentors, yet concerns have arisen about antibiotic resistance among the LAB. Here, we report on mechanisms used by 32 LAB isolates from eight different US bioethanol facilities to persist under conditions of antibiotic stress. Minimum inhibitory concentration assays with penicillin, erythromycin, and virginiamycin revealed broad resistance to each of the antibiotics as well as high levels of resistance to individual antibiotics. Phenotypic assays revealed that antibiotic inactivation mechanisms contributed to the high levels of individual resistances among the isolates, especially to erythromycin and virginiamycin, yet none of the isolates appeared to use a β-lactamase. Biofilm formation was noted among the majority of the isolates and may contribute to persistence under low levels of antibiotics. Nearly all of the isolates carried at least one canonical antibiotic resistance gene and many carried more than one. The erythromycin ribosomal methyltransferase (erm) gene class was found in 19 of 32 isolates, yet a number of these isolates exhibit little to no resistance to erythromycin. The erm genes were present in 15 isolates that encoded more than one antibiotic resistance mechanism, suggestive of potential genetic linkages.

  17. Antibiotic susceptibility in benzalkonium chloride-resistant and -susceptible Listeria monocytogenes strains.

    PubMed

    Ortiz, Sagrario; López, Pilar; López, Victoria; Martínez-Suárez, Joaquín V

    2014-07-01

    This study aimed to investigate whether Listeria monocytogenes strains with resistance to a commonly used biocide display any cross-resistance to antibiotics. Using pulsed-field gel electrophoresis (PFGE), 29 different PFGE types were previously identified in an Iberian pig abattoir and processing plant. Only three PFGE types were resistant to benzalkonium chloride (BAC), but they represented a significant proportion of the PFGE types surviving in the plant after 4 years. In the present study, a subset of 29 strains, representing the 29 different PFGE types, underwent antibiotic susceptibility testing. Antibiotic susceptibility was assessed by Etest, utilizing 12 commonly prescribed antibiotics. All of the 29 strains were susceptible to all of the antibiotics tested. The study revealed that this group of different PFGE types of L. monocytogenes, including those resistant to BAC, possesses uniform sensitivity to antibiotics.

  18. Multidrug efflux pumps in Gram-negative bacteria and their role in antibiotic resistance.

    PubMed

    Blair, Jessica M A; Richmond, Grace E; Piddock, Laura J V

    2014-01-01

    Gram-negative bacteria express a plethora of efflux pumps that are capable of transporting structurally varied molecules, including antibiotics, out of the bacterial cell. This efflux lowers the intracellular antibiotic concentration, allowing bacteria to survive at higher antibiotic concentrations. Overexpression of some efflux pumps can cause clinically relevant levels of antibiotic resistance in Gram-negative pathogens. This review discusses the role of efflux in resistance of clinical isolates of Gram-negative bacteria, the regulatory mechanisms that control efflux pump expression, the recent advances in our understanding of efflux pump structure and how inhibition of efflux is a promising future strategy for tackling multidrug resistance in Gram-negative pathogens.

  19. Improved antibiotic resistance gene cassette for marker exchange mutagenesis in Ralstonia solanacearum and Burkholderia species.

    PubMed

    Um, Hae Young; Chung, Eunsook; Lee, Jai-Heon; Lee, Seon-Woo

    2011-04-01

    Marker exchange mutagenesis is a fundamental approach to understanding gene function at a molecular level in bacteria. New plasmids carrying a kanamycin resistance gene or a trimethoprim resistance gene were constructed to provide antibiotic resistance cassettes for marker exchange mutagenesis in Ralstonia solanacearum and many antibiotic-resistant Burkholderia spp. Insertion sequences present in the flanking sequences of the antibiotic resistance cassette were removed to prevent aberrant gene replacement and polar mutation during mutagenesis in wild-type bacteria. Plasmids provided in this study would be convenient for use in gene cassettes for gene replacement in other Gram-negative bacteria.

  20. Studying Modification of Aminoglycoside Antibiotics by Resistance-Causing Enzymes via Microarray

    PubMed Central

    Disney, Matthew D.

    2013-01-01

    Widespread bacterial resistance to antibiotics is a significant public health concern. To remain a step ahead of evolving bacteria, new methods to study resistance to antibacterials and to uncover novel antibiotics that evade resistance are urgently needed. Herein, microarray-based methods that have been developed to study aminoglycoside modification by resistance-causing enzymes are reviewed. These arrays can also be used to study the binding of aminoglycoside antibiotics to a mimic of their therapeutic target, the rRNA aminoacyl site (A-site), and how modification by resistance-causing enzymes affects their abilities to bind RNA. PMID:22057534

  1. Studying modification of aminoglycoside antibiotics by resistance-causing enzymes via microarray.

    PubMed

    Disney, Matthew D

    2012-01-01

    Widespread bacterial resistance to antibiotics is a significant public health concern. To remain a step ahead of evolving bacteria, new methods to study resistance to antibacterials and to uncover novel antibiotics that evade resistance are urgently needed. Herein, microarray-based methods that have been developed to study aminoglycoside modification by resistance-causing enzymes are reviewed. These arrays can also be used to study the binding of aminoglycoside antibiotics to a mimic of their therapeutic target, the rRNA aminoacyl site (A-site), and how modification by resistance-causing enzymes affects their abilities to bind RNA.

  2. Antibiotic resistance genes detected in the marine sponge Petromica citrina from Brazilian coast.

    PubMed

    Laport, Marinella Silva; Pontes, Paula Veronesi Marinho; Dos Santos, Daniela Silva; Santos-Gandelman, Juliana de Fátima; Muricy, Guilherme; Bauwens, Mathieu; Giambiagi-deMarval, Marcia; George, Isabelle

    2016-01-01

    Although antibiotic-resistant pathogens pose a significant threat to human health, the environmental reservoirs of the resistance determinants are still poorly understood. This study reports the detection of resistance genes (ermB, mecA, mupA, qnrA, qnrB and tetL) to antibiotics among certain culturable and unculturable bacteria associated with the marine sponge Petromica citrina. The antimicrobial activities elicited by P. citrina and its associated bacteria are also described. The results indicate that the marine environment could play an important role in the development of antibiotic resistance and the dissemination of resistance genes among bacteria.

  3. Antibiotic resistance of Campylobacter in raw retail chickens and imported chicken portions.

    PubMed Central

    Wilson, I. G.

    2003-01-01

    Campylobacter isolates from raw retail chickens (n = 434) sampled between 1998 and 2000 were tested for resistance to 12 antibiotics. Among 208 campylobacters tested, more than 90% of isolates were susceptible to 4 out of 9 antibiotics (nalidixic acid, erythromycin, chloramphenicol and gentamicin). Most campylobacters were resistant to 3 antibiotics and multiple resistance was found in 4%. Ciprofloxacin resistance was 11%. Campylobacter contamination (28%) in imported chickens (n = 150) was almost half that found in local whole chickens (50%), but the resistance of imported isolates (n = 42) was similar to that of local campylobacters. Resistance in isolates from imported chicken breasts was generally more common, but to only 4 antibiotics. Resistance patterns of chicken isolates were compared to human clinical isolates (n = 494), and a greater similarity was found between the clinical and local isolates than with imported campylobacters. Lower chloramphenicol resistance was found in clinical Campylobacter isolates than in those from chicken sources. PMID:14959786

  4. Mechanism of resistance to macrolide-lincosamide-streptogramin antibiotics in Streptococcus thermophilus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Resistance to macrolide-lincosamide-streptogramin (MLS) group antibiotics in the dairy bacterium Streptococcus thermophilus (ST) is documented but the mechanism of resistance has not been elucidated. MIC values for erythromycin (Erm), azithromycin (Azm), tylosin (Tyl), spiramycin (Spm), pristinamyci...

  5. Resistant Traits in Digital Organisms Do Not Revert Preselection Status despite Extended Deselection: Implications to Microbial Antibiotics Resistance

    PubMed Central

    Castillo, Clarence F. G.; Ling, Maurice H. T.

    2014-01-01

    Antibiotics resistance is a serious biomedical issue as formally susceptible organisms gain resistance under its selective pressure. There have been contradictory results regarding the prevalence of resistance following withdrawal and disuse of the specific antibiotics. Here, we use experimental evolution in “digital organisms” to examine the rate of gain and loss of resistance under the assumption that there is no fitness cost for maintaining resistance. Our results show that selective pressure is likely to result in maximum resistance with respect to the selective pressure. During deselection as a result of disuse of the specific antibiotics, a large initial loss and prolonged stabilization of resistance are observed, but resistance is not lost to the stage of preselection. This suggests that a pool of partial persists organisms persist long after withdrawal of selective pressure at a relatively constant proportion. Hence, contradictory results regarding the prevalence of resistance following withdrawal and disuse of the specific antibiotics may be a statistical variation about constant proportion. Our results also show that subsequent reintroduction of the same selective pressure results in rapid regain of maximal resistance. Thus, our simulation results suggest that complete elimination of specific antibiotics resistance is unlikely after the disuse of antibiotics once a resistant pool of microorganisms has been established. PMID:24977157

  6. Resistant traits in digital organisms do not revert preselection status despite extended deselection: implications to microbial antibiotics resistance.

    PubMed

    Castillo, Clarence F G; Ling, Maurice H T

    2014-01-01

    Antibiotics resistance is a serious biomedical issue as formally susceptible organisms gain resistance under its selective pressure. There have been contradictory results regarding the prevalence of resistance following withdrawal and disuse of the specific antibiotics. Here, we use experimental evolution in "digital organisms" to examine the rate of gain and loss of resistance under the assumption that there is no fitness cost for maintaining resistance. Our results show that selective pressure is likely to result in maximum resistance with respect to the selective pressure. During deselection as a result of disuse of the specific antibiotics, a large initial loss and prolonged stabilization of resistance are observed, but resistance is not lost to the stage of preselection. This suggests that a pool of partial persists organisms persist long after withdrawal of selective pressure at a relatively constant proportion. Hence, contradictory results regarding the prevalence of resistance following withdrawal and disuse of the specific antibiotics may be a statistical variation about constant proportion. Our results also show that subsequent reintroduction of the same selective pressure results in rapid regain of maximal resistance. Thus, our simulation results suggest that complete elimination of specific antibiotics resistance is unlikely after the disuse of antibiotics once a resistant pool of microorganisms has been established.

  7. Removal of antibiotics and antibiotic resistance genes from domestic sewage by constructed wetlands: Effect of flow configuration and plant species.

    PubMed

    Chen, Jun; Ying, Guang-Guo; Wei, Xiao-Dong; Liu, You-Sheng; Liu, Shuang-Shuang; Hu, Li-Xin; He, Liang-Ying; Chen, Zhi-Feng; Chen, Fan-Rong; Yang, Yong-Qiang

    2016-11-15

    This study aims to investigate the removal of antibiotics and antibiotic resistance genes (ARGs) in raw domestic wastewater by various mesocosm-scale constructed wetlands (CWs) with different flow configurations or plant species including the constructed wetland with or without plant. Six mesocosm-scale CWs with three flow types (surface flow, horizontal subsurface flow and vertical subsurface flow) and two plant species (Thaliadealbata Fraser and Iris tectorum Maxim) were set up in the outdoor. 8 antibiotics including erythromycin-H2O (ETM-H2O), monensin (MON), clarithromycin (CTM), leucomycin (LCM), sulfamethoxazole (SMX), trimethoprim (TMP), sulfamethazine (SMZ) and sulfapyridine (SPD) and 12 genes including three sulfonamide resistance genes (sul1, sul2 and sul3), four tetracycline resistance genes (tetG, tetM, tetO and tetX), two macrolide resistance genes (ermB and ermC), two chloramphenicol resistance genes (cmlA and floR) and 16S rRNA (bacteria) were determined in different matrices (water, particle, substrate and plant phases) from the mesocosm-scale systems. The aqueous removal efficiencies of total antibiotics ranged from 75.8 to 98.6%, while those of total ARGs varied between 63.9 and 84.0% by the mesocosm-scale CWs. The presence of plants was beneficial to the removal of pollutants, and the subsurface flow CWs had higher pollutant removal than the surface flow CWs, especially for antibiotics. According to the mass balance analysis, the masses of all detected antibiotics during the operation period were 247,000, 4920-10,600, 0.05-0.41 and 3500-60,000μg in influent, substrate, plant and effluent of the mesocosm-scale CWs. In the CWs, biodegradation, substrate adsorption and plant uptake all played certain roles in reducing the loadings of nutrients, antibiotics and ARGs, but biodegradation was the most important process in the removal of these pollutants.

  8. Modelling proteins' hidden conformations to predict antibiotic resistance

    NASA Astrophysics Data System (ADS)

    Hart, Kathryn M.; Ho, Chris M. W.; Dutta, Supratik; Gross, Michael L.; Bowman, Gregory R.

    2016-10-01

    TEM β-lactamase confers bacteria with resistance to many antibiotics and rapidly evolves activity against new drugs. However, functional changes are not easily explained by differences in crystal structures. We employ Markov state models to identify hidden conformations and explore their role in determining TEM's specificity. We integrate these models with existing drug-design tools to create a new technique, called Boltzmann docking, which better predicts TEM specificity by accounting for conformational heterogeneity. Using our MSMs, we identify hidden states whose populations correlate with activity against cefotaxime. To experimentally detect our predicted hidden states, we use rapid mass spectrometric footprinting and confirm our models' prediction that increased cefotaxime activity correlates with reduced Ω-loop flexibility. Finally, we design novel variants to stabilize the hidden cefotaximase states, and find their populations predict activity against cefotaxime in vitro and in vivo. Therefore, we expect this framework to have numerous applications in drug and protein design.

  9. Antiplasmid activity: loss of bacterial resistance to antibiotics.

    PubMed

    Molnár, J; Földeák, S; Nakamura, M J; Rausch, H; Domonkos, K; Szabó, M

    1992-01-01

    The antiplasmid activity of tricyclic compounds, e.g. phenothiazines, dibenzoazepines, dibenzocykloheptene derivatives and some stereoisomers, was shown on E. coli in vitro. Some ring-substituted phenothiazine and cannabis derivatives had only an antibacterial effect. Promethazine, a selected phenothiazine, cured antibiotic resistance and lactose fermentation of E.coli, tumour inducing ability of Agrobacterium tumefaciens and nodule formation of Rhizobium meliloti. Plasmids of different E.coli strains were eliminated with varying frequency. The antiplasmid activity of the compounds can be due to the increased membrane permeability. Inhibition of DNA gyrase and complex formation with the supercoiled form of plasmid DNA can lead to the cessation of plasmid replication in the bacterial cells. In addition, in vivo plasmid curing was demonstrated at a low frequency.

  10. Facing antibiotic resistance: Staphylococcus aureus phages as a medical tool.

    PubMed

    Kaźmierczak, Zuzanna; Górski, Andrzej; Dąbrowska, Krystyna

    2014-07-01

    Staphylococcus aureus is a common and often virulent pathogen in humans. This bacterium is widespread, being present on the skin and in the nose of healthy people. Staphylococcus aureus can cause infections with severe outcomes ranging from pustules to sepsis and death. The introduction of antibiotics led to a general belief that the problem of bacterial infections would be solved. Nonetheless, pathogens including staphylococci have evolved mechanisms of drug resistance. Among current attempts to address this problem, phage therapy offers a promising alternative to combat staphylococcal infections. Here, we present an overview of current knowledge on staphylococcal infections and bacteriophages able to kill Staphylococcus, including experimental studies and available data on their clinical use.

  11. Facing Antibiotic Resistance: Staphylococcus aureus Phages as a Medical Tool

    PubMed Central

    Kaźmierczak, Zuzanna; Górski, Andrzej; Dąbrowska, Krystyna

    2014-01-01

    Staphylococcus aureus is a common and often virulent pathogen in humans. This bacterium is widespread, being present on the skin and in the nose of healthy people. Staphylococcus aureus can cause infections with severe outcomes ranging from pustules to sepsis and death. The introduction of antibiotics led to a general belief that the problem of bacterial infections would be solved. Nonetheless, pathogens including staphylococci have evolved mechanisms of drug resistance. Among current attempts to address this problem, phage therapy offers a promising alternative to combat staphylococcal infections. Here, we present an overview of current knowledge on staphylococcal infections and bacteriophages able to kill Staphylococcus, including experimental studies and available data on their clinical use. PMID:24988520

  12. Transport of antibiotic-resistant Escherichia coli in a public rural karst water supply

    NASA Astrophysics Data System (ADS)

    Laroche, Emilie; Petit, Fabienne; Fournier, Matthieu; Pawlak, Barbara

    2010-10-01

    SummaryThe goal of this study was to determine the conditions promoting the transport of antibiotic-resistant faecal bacteria, in a rural karst system providing drinking water (Northwest France). For this purpose, the resistance of the Escherichia coli population (436 isolates) to 17 antibiotics was investigated by analysing water samples from four representative interconnected sites: a creek, a swallow hole, a spring, and a well. The samples were collected during four contrasting hydrologic and grazing periods. The transport of resistant E. coli from the creek to the well appeared to be dominated by run-off and leaching phenomena. Less than 7% of the E. coli isolated during a wet period without grazing or during a dry period with grazing were antibiotic-resistant, whereas, during rainfall events with grazing, between 30% and 55% of the E. coli detected were resistant; 10-23% of these isolates were resistant to two or three antibiotics. The resistance most often found was to either chloramphenicol or tetracycline. To better describe the dynamics of the antibiotic-resistant population of E. coli entering the karst aquifer, the swallow hole was monitored over a 24-h period during a rainfall event (90 isolates). The antibiotic resistance of E. coli isolates and the occurrence of class 1 integrons, genetic elements involved multi-resistance, were determined. The origin of this E. coli population was also investigated. This monitoring demonstrated that multi-antibiotic-resistant E. coli, representing 23% of the total population, infiltrated the karst aquifer at the peak of a rainfall event, with some isolates being resistant to up to eight antibiotics. No intI1 gene was detected. The search for the origin of the resistant E. coli isolated during this rainfall event demonstrated that they were of both animal and human origin. This work demonstrates that drinking water resources taken from the groundwater in a rural karst terrain is vulnerable to contamination by

  13. Intrinsic Macrolide Resistance in Mycobacterium smegmatis Is Conferred by a Novel erm Gene, erm(38)

    PubMed Central

    Nash, Kevin A.

    2003-01-01

    High-level, acquired macrolide resistance in mycobacteria is conferred by mutation within the 23S rRNA gene. However, several mycobacteria are naturally resistant to macrolides, including the Mycobacterium smegmatis group and Mycobacterium tuberculosis complex. Thus, the aim of this study was to characterize this resistance. Intrinsic macrolide resistance in M. smegmatis was inducible and showed cross-resistance to lincosamides but not to streptogramin B (i.e., ML resistance). A similar phenotype was found with Mycobacterium microti and macrolide-resistant Mycobacterium fortuitum. A search of the DNA sequence data for M. smegmatis strain mc2155 identified a novel erm gene, erm(38), and expression analysis showed that erm(38) RNA levels increased >10-fold after a 2-h incubation with macrolide. Inducible ML resistance was not expressed by an erm(38) knockout mutant, and complementation of this mutant with intact erm(38) in trans resulted in high-level ML resistance (e.g., clarithromycin MIC of >512 μg/ml). Thus, the results indicate that erm(38) confers the intrinsic ML resistance of M. smegmatis. Southern blot analysis with an erm(38)-specific probe indicated that a similar gene may be present in macrolide-resistant M. fortuitum. This finding, with the presence of the erm(37) gene (Rv1988) in the M. tuberculosis complex, suggests that such genes are widespread in mycobacteria with intrinsic macrolide resistance. PMID:14506008

  14. Resistance determinants and their association with different transposons in the antibiotic-resistant Streptococcus pneumoniae.

    PubMed

    Korona-Glowniak, Izabela; Siwiec, Radoslaw; Malm, Anna

    2015-01-01

    Multiple resistance of Streptococcus pneumoniae is generally associated with their unique recombination-mediated genetic plasticity and possessing the mobile genetic elements. The aim of our study was to detect antibiotic resistance determinants and conjugative transposons in 138 antibiotic-resistant pneumococcal strains isolated from nasopharynx of healthy young children from Lublin, Poland. These strains resistant to tetracycline and/or to chloramphenicol/erythromycin/clindamycin were tested by PCR using the specific genes as markers. The presence of Tn916 family transposons, carrying tet(M) and int/xisTn916, was observed in all of the tested strains. Tn916 was detected in 16 strains resistant only to tetracycline. Tn6002 and Tn3872-related element were found among 99 erm(B)-carrying strains (83.8% and 3.0%, resp.). Eight strains harbouring mef(E) and erm(B) genes were detected, suggesting the presence of Tn2010 and Tn2017 transposons. Among 101 chloramphenicol-resistant strains, two variants of Tn5252-related transposon were distinguished depending on the presence of int/xis5252 genes specific for cat gene-containing Tn5252 (75.2% of strains) or int Sp23FST81 gene, specific for cat-containing ICESp23FST81 element (24.8% of strains). In 6 strains Tn916-like and Tn5252-like elements formed a Tn5253-like structure. Besides clonal dissemination of resistant strains of pneumococci in the population, horizontal transfer of conjugative transposons is an important factor of the high prevalence of antibiotic resistance.

  15. Outer Membrane Proteins form Specific Patterns in Antibiotic-Resistant Edwardsiella tarda

    PubMed Central

    Peng, Bo; Wang, Chao; Li, Hui; Su, Yu-bin; Ye, Jin-zhou; Yang, Man-jun; Jiang, Ming; Peng, Xuan-xian

    2017-01-01

    Outer membrane proteins of Gram-negative bacteria play key roles in antibiotic resistance. However, it is unknown whether outer membrane proteins that respond to antibiotics behave in a specific manner. The present study specifically investigated the differentially expressed outer membrane proteins of an antibiotic-resistant bacterium, Edwardsiella tarda, a Gram-negative pathogen that can lead to unnecessary mass medication of antimicrobials and consequently resistance development in aquaculture and a spectrum of intestinal and extraintestinal diseases in humans. The comparison of a clinically isolated strain to the laboratory derived kanamycin-, tetracycline-, or chloramphenicol-resistant strains identified their respective outer membrane proteins expression patterns, which are distinct to each other. Similarly, the same approach was utilized to profile the patterns in double antibiotic-resistant bacteria. Surprisingly, one pattern is always dominant over the other as to these three antibiotics; the pattern of chloramphenicol is over tetracycline, which is over kanamycin. This type of pattern was also confirmed in clinically relevant multidrug-resistant bacteria. In addition, the presence of plasmid encoding antibiotic-resistant genes also alters the outer membrane protein profile in a similar manner. Our results demonstrate that bacteria adapt the antibiotic stress through the regulation of outer membrane proteins expression. And more importantly, different outer membrane protein profiles were required to cope with different antibiotics. This type of specific pattern provides the rationale for the development of novel strategy to design outer membrane protein arrays to identify diverse multidrug resistance profiles as biomarkers for clinical medication. PMID:28210241

  16. Interrogating the plasmidome to determine antibiotic resistance gene mobility within the swine fecal microbiota

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The use of antibiotics in animal production has been highlighted as a key contributor to the increasing prevalence of antibiotic resistance in agroecosystems. Gram negative bacteria, such as the Enterobacteriaceae, are important facilitators for resistance gene dissemination in the environment and i...

  17. Irrigation waters and pipe-based biofilms as sources for antibiotic-resistant bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The presence of antibiotic-resistant bacteria in environmental surface waters has gained recent attention. Wastewater- and drinking water distribution systems are known to disseminate antibiotic-resistant bacteria, with the biofilms that form on the inner-surfaces of the pipeline as a hotspot for pr...

  18. Antimicrobial Chemicals Are Associated with Elevated Antibiotic Resistance Genes in the Indoor Dust Microbiome

    PubMed Central

    2016-01-01

    Antibiotic resistance is increasingly widespread, largely due to human influence. Here, we explore the relationship between antibiotic resistance genes and the antimicrobial chemicals triclosan, triclocarban, and methyl-, ethyl-, propyl-, and butylparaben in the dust microbiome. Dust samples from a mixed-use athletic and educational facility were subjected to microbial and chemical analyses using a combination of 16S rRNA amplicon sequencing, shotgun metagenome sequencing, and liquid chromatography tandem mass spectrometry. The dust resistome was characterized by identifying antibiotic resistance genes annotated in the Comprehensive Antibiotic Resistance Database (CARD) from the metagenomes of each sample using the Short, Better Representative Extract Data set (ShortBRED). The three most highly abundant antibiotic resistance genes were tet(W), blaSRT-1, and erm(B). The complete dust resistome was then compared against the measured concentrations of antimicrobial chemicals, which for triclosan ranged from 0.5 to 1970 ng/g dust. We observed six significant positive associations between the concentration of an antimicrobial chemical and the relative abundance of an antibiotic resistance gene, including one between the ubiquitous antimicrobial triclosan and erm(X), a 23S rRNA methyltransferase implicated in resistance to several antibiotics. This study is the first to look for an association between antibiotic resistance genes and antimicrobial chemicals in dust. PMID:27599587

  19. Outer Membrane Proteins form Specific Patterns in Antibiotic-Resistant Edwardsiella tarda.

    PubMed

    Peng, Bo; Wang, Chao; Li, Hui; Su, Yu-Bin; Ye, Jin-Zhou; Yang, Man-Jun; Jiang, Ming; Peng, Xuan-Xian

    2017-01-01

    Outer membrane proteins of Gram-negative bacteria play key roles in antibiotic resistance. However, it is unknown whether outer membrane proteins that respond to antibiotics behave in a specific manner. The present study specifically investigated the differentially expressed outer membrane proteins of an antibiotic-resistant bacterium, Edwardsiella tarda, a Gram-negative pathogen that can lead to unnecessary mass medication of antimicrobials and consequently resistance development in aquaculture and a spectrum of intestinal and extraintestinal diseases in humans. The comparison of a clinically isolated strain to the laboratory derived kanamycin-, tetracycline-, or chloramphenicol-resistant strains identified their respective outer membrane proteins expression patterns, which are distinct to each other. Similarly, the same approach was utilized to profile the patterns in double antibiotic-resistant bacteria. Surprisingly, one pattern is always dominant over the other as to these three antibiotics; the pattern of chloramphenicol is over tetracycline, which is over kanamycin. This type of pattern was also confirmed in clinically relevant multidrug-resistant bacteria. In addition, the presence of plasmid encoding antibiotic-resistant genes also alters the outer membrane protein profile in a similar manner. Our results demonstrate that bacteria adapt the antibiotic stress through the regulation of outer membrane proteins expression. And more importantly, different outer membrane protein profiles were required to cope with different antibiotics. This type of specific pattern provides the rationale for the development of novel strategy to design outer membrane protein arrays to identify diverse multidrug resistance profiles as biomarkers for clinical medication.

  20. Clusters of antibiotic resistance genes enriched together stay together in swine agriculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Antibiotic resistance has developed into a worldwide health risk. The nature and extent of the contribution of animal agriculture to the evolution of antibiotic resistance in bacterial communities remains unclear. Using quantitative polymerase chain reaction (PCR) in tandem with next-generation sequ...