Science.gov

Sample records for intrinsic antibiotic resistance

  1. 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 ...

  2. Antibiotic Resistance

    MedlinePlus

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

  3. Glycopeptide Antibiotic To Overcome the Intrinsic Resistance of Gram-Negative Bacteria.

    PubMed

    Yarlagadda, Venkateswarlu; Manjunath, Goutham B; Sarkar, Paramita; Akkapeddi, Padma; Paramanandham, Krishnamoorthy; Shome, Bibek R; Ravikumar, Raju; Haldar, Jayanta

    2016-02-12

    The emergence of drug resistance along with a declining pipeline of clinically useful antibiotics has made it vital to develop more effective antimicrobial therapeutics, particularly against difficult-to-treat Gram-negative pathogens (GNPs). Many antibacterial agents, including glycopeptide antibiotics such as vancomycin, are inherently inactive toward GNPs because of their inability to cross the outer membrane of these pathogens. Here, we demonstrate, for the first time, lipophilic cationic (permanent positive charge) vancomycin analogues were able to permeabilize the outer membrane of GNPs and overcome the inherent resistance of GNPs toward glycopeptides. Unlike vancomycin, these analogues were shown to have a high activity against a variety of multidrug-resistant clinical isolates such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. In the murine model of carbapenem-resistant A. baumannii infection, the optimized compound showed potent activity with no observed toxicity. The notable activity of these compounds is attributed to the incorporation of new membrane disruption mechanisms (cytoplasmic membrane depolarization along with outer and inner (cytoplasmic) membrane permeabilization) into vancomycin. Therefore, our results indicate the potential of the present vancomycin analogues to be used against drug-resistant GNPs, thus strengthening the antibiotic arsenal for combating Gram-negative bacterial infections. PMID:27624964

  4. 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.

  5. 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.

  6. Mutant Alleles of lptD Increase the Permeability of Pseudomonas aeruginosa and Define Determinants of Intrinsic Resistance to Antibiotics

    PubMed Central

    Grabowicz, Marcin

    2015-01-01

    Gram-negative bacteria provide a particular challenge to antibacterial drug discovery due to their cell envelope structure. Compound entry is impeded by the lipopolysaccharide (LPS) of the outer membrane (OM), and those molecules that overcome this barrier are often expelled by multidrug efflux pumps. Understanding how efflux and permeability affect the ability of a compound to reach its target is paramount to translating in vitro biochemical potency to cellular bioactivity. Herein, a suite of Pseudomonas aeruginosa strains were constructed in either a wild-type or efflux-null background in which mutations were engineered in LptD, the final protein involved in LPS transport to the OM. These mutants were demonstrated to be defective in LPS transport, resulting in compromised barrier function. Using isogenic strain sets harboring these newly created alleles, we were able to define the contributions of permeability and efflux to the intrinsic resistance of P. aeruginosa to a variety of antibiotics. These strains will be useful in the design and optimization of future antibiotics against Gram-negative pathogens. PMID:26596941

  7. Facts about Antibiotic Resistance

    MedlinePlus

    ... Trends and Cost Español: Datos breves Facts about Antibiotic Resistance Antibiotic resistance has been called one of the world’s most ... antibiotic use is a key strategy to control antibiotic resistance. Antibiotic resistance in children is of particular concern ...

  8. 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

  9. 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 ...

  10. Reversibility of antibiotic resistance

    PubMed Central

    2014-01-01

    Although theoretically attractive, the reversibility of resistance has proven difficult in practice, even though antibiotic resistance mechanisms induce a fitness cost to the bacterium. Associated resistance to other antibiotics and compensatory mutations seem to ameliorate the effect of antibiotic interventions in the community. In this paper the current understanding of the concepts of reversibility of antibiotic resistance and the interventions performed in hospitals and in the community are reviewed. PMID:24836051

  11. Antibiotic Resistance Questions and Answers

    MedlinePlus

    ... on the Farm Get Smart About Antibiotics Week Antibiotic Resistance Questions and Answers Language: English Español (Spanish) Recommend ... Many ear infections Top of Page Questions about Antibiotic Resistance Examples of How Antibiotic Resistance Spreads Click for ...

  12. 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

  13. 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

  14. 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)

  15. 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

    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.

  16. 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

  17. 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. PMID:27620956

  18. 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

  19. Mechanisms of Antibiotic Resistance.

    PubMed

    Munita, Jose M; Arias, Cesar A

    2016-04-01

    Emergence of resistance among the most important bacterial pathogens is recognized as a major public health threat affecting humans worldwide. Multidrug-resistant organisms have not only emerged 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 to 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

  20. Tackling antibiotic resistance.

    PubMed

    Bush, Karen; Courvalin, Patrice; Dantas, Gautam; Davies, Julian; Eisenstein, Barry; Huovinen, Pentti; Jacoby, George A; Kishony, Roy; Kreiswirth, Barry N; Kutter, Elizabeth; Lerner, Stephen A; Levy, Stuart; Lewis, Kim; Lomovskaya, Olga; Miller, Jeffrey H; Mobashery, Shahriar; Piddock, Laura J V; Projan, Steven; Thomas, Christopher M; Tomasz, Alexander; Tulkens, Paul M; Walsh, Timothy R; Watson, James D; Witkowski, Jan; Witte, Wolfgang; Wright, Gerry; Yeh, Pamela; Zgurskaya, Helen I

    2011-11-02

    The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable but can nevertheless be controlled, and it must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of 30 scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, USA, from 16 to 18 May 2011. From these discussions there emerged a priority list of steps that need to be taken to resolve this global crisis.

  1. Tackling antibiotic resistance

    PubMed Central

    Bush, Karen; Courvalin, Patrice; Dantas, Gautam; Davies, Julian; Eisenstein, Barry; Huovinen, Pentti; Jacoby, George A.; Kishony, Roy; Kreiswirth, Barry N.; Kutter, Elizabeth; Lerner, Stephen A.; Levy, Stuart; Lewis, Kim; Lomovskaya, Olga; Miller, Jeffrey H.; Mobashery, Shahriar; Piddock, Laura J. V.; Projan, Steven; Thomas, Christopher M.; Tomasz, Alexander; Tulkens, Paul M.; Walsh, Timothy R.; Watson, James D.; Witkowski, Jan; Witte, Wolfgang; Wright, Gerry; Yeh, Pamela; Zgurskaya, Helen I.

    2014-01-01

    The development and spread of antibiotic resistance in bacteria is a universal threat to both humans and animals that is generally not preventable, but can nevertheless be controlled and must be tackled in the most effective ways possible. To explore how the problem of antibiotic resistance might best be addressed, a group of thirty scientists from academia and industry gathered at the Banbury Conference Centre in Cold Spring Harbor, New York, May 16-18, 2011. From these discussions emerged a priority list of steps that need to be taken to resolve this global crisis. PMID:22048738

  2. 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)

  3. 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

  4. Surveillance of antibiotic resistance

    PubMed Central

    Johnson, Alan P.

    2015-01-01

    Surveillance involves the collection and analysis of data for the detection and monitoring of threats to public health. Surveillance should also inform as to the epidemiology of the threat and its burden in the population. A further key component of surveillance is the timely feedback of data to stakeholders with a view to generating action aimed at reducing or preventing the public health threat being monitored. Surveillance of antibiotic resistance involves the collection of antibiotic susceptibility test results undertaken by microbiology laboratories on bacteria isolated from clinical samples sent for investigation. Correlation of these data with demographic and clinical data for the patient populations from whom the pathogens were isolated gives insight into the underlying epidemiology and facilitates the formulation of rational interventions aimed at reducing the burden of resistance. This article describes a range of surveillance activities that have been undertaken in the UK over a number of years, together with current interventions being implemented. These activities are not only of national importance but form part of the international response to the global threat posed by antibiotic resistance. PMID:25918439

  5. Antibiotic resistance: an ecological imbalance.

    PubMed

    Levy, S B

    1997-01-01

    Antibiotic resistance thwarts the treatment of infectious diseases worldwide. Although a number of factors can be identified which contribute to the problem, clearly the antibiotic as a selective agent and the resistance gene as the vehicle of resistance are the two most important, making up a 'drug resistance equation'. Both are needed in order for a clinical problem to arise. Given sufficient time and quantity of antibiotic, drug resistance will eventually appear. But a public health problem is not inevitable if the two components of the drug resistance equation are kept in check. Enhancing the emergence of resistance is the case by which resistance determinants and resistant bacteria can spread locally and globally, selected by widespread use of the same antibiotics in people, animal husbandry and agriculture. Antibiotics are societal drugs. Each individual use contributes to the sum total of society's antibiotic exposure. In a broader sense, the resistance problem is ecological. In the framework of natural competition between susceptible and resistant bacteria, antibiotic use has encouraged growth of the resistant strains, leading to an imbalance in prior relationships between susceptible and resistant bacteria. To restore efficacy to earlier antibiotics and to maintain the success of new antibiotics that are introduced, we need to use antibiotics in a way which assures an ecological balance that favours the predominance of susceptible bacterial flora.

  6. 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.

  7. The Comprehensive Antibiotic Resistance Database

    PubMed Central

    McArthur, Andrew G.; Waglechner, Nicholas; Nizam, Fazmin; Yan, Austin; Azad, Marisa A.; Baylay, Alison J.; Bhullar, Kirandeep; Canova, Marc J.; De Pascale, Gianfranco; Ejim, Linda; Kalan, Lindsay; King, Andrew M.; Koteva, Kalinka; Morar, Mariya; Mulvey, Michael R.; O'Brien, Jonathan S.; Pawlowski, Andrew C.; Piddock, Laura J. V.; Spanogiannopoulos, Peter; Sutherland, Arlene D.; Tang, Irene; Taylor, Patricia L.; Thaker, Maulik; Wang, Wenliang; Yan, Marie; Yu, Tennison

    2013-01-01

    The field of antibiotic drug discovery and the monitoring of new antibiotic resistance elements have yet to fully exploit the power of the genome revolution. Despite the fact that the first genomes sequenced of free living organisms were those of bacteria, there have been few specialized bioinformatic tools developed to mine the growing amount of genomic data associated with pathogens. In particular, there are few tools to study the genetics and genomics of antibiotic resistance and how it impacts bacterial populations, ecology, and the clinic. We have initiated development of such tools in the form of the Comprehensive Antibiotic Research Database (CARD; http://arpcard.mcmaster.ca). The CARD integrates disparate molecular and sequence data, provides a unique organizing principle in the form of the Antibiotic Resistance Ontology (ARO), and can quickly identify putative antibiotic resistance genes in new unannotated genome sequences. This unique platform provides an informatic tool that bridges antibiotic resistance concerns in health care, agriculture, and the environment. PMID:23650175

  8. Antibiotic resistance in wild birds

    PubMed Central

    Bonnedahl, Jonas

    2014-01-01

    Wild birds have been postulated as sentinels, reservoirs, and potential spreaders of antibiotic resistance. Antibiotic-resistant bacteria have been isolated from a multitude of wild bird species. Several studies strongly indicate transmission of resistant bacteria from human rest products to wild birds. There is evidence suggesting that wild birds can spread resistant bacteria through migration and that resistant bacteria can be transmitted from birds to humans and vice versa. Through further studies of the spatial and temporal distribution of resistant bacteria in wild birds, we can better assess their role and thereby help to mitigate the increasing global problem of antibiotic resistance. PMID:24697355

  9. Antibiotic resistance in wild birds.

    PubMed

    Bonnedahl, Jonas; Järhult, Josef D

    2014-05-01

    Wild birds have been postulated as sentinels, reservoirs, and potential spreaders of antibiotic resistance. Antibiotic-resistant bacteria have been isolated from a multitude of wild bird species. Several studies strongly indicate transmission of resistant bacteria from human rest products to wild birds. There is evidence suggesting that wild birds can spread resistant bacteria through migration and that resistant bacteria can be transmitted from birds to humans and vice versa. Through further studies of the spatial and temporal distribution of resistant bacteria in wild birds, we can better assess their role and thereby help to mitigate the increasing global problem of antibiotic resistance. PMID:24697355

  10. The Prehistory of Antibiotic Resistance.

    PubMed

    Perry, Julie; Waglechner, Nicholas; Wright, Gerard

    2016-01-01

    Antibiotic resistance is a global problem that is reaching crisis levels. The global collection of resistance genes in clinical and environmental samples is the antibiotic "resistome," and is subject to the selective pressure of human activity. The origin of many modern resistance genes in pathogens is likely environmental bacteria, including antibiotic producing organisms that have existed for millennia. Recent work has uncovered resistance in ancient permafrost, isolated caves, and in human specimens preserved for hundreds of years. Together with bioinformatic analyses on modern-day sequences, these studies predict an ancient origin of resistance that long precedes the use of antibiotics in the clinic. Understanding the history of antibiotic resistance is important in predicting its future evolution. PMID:27252395

  11. Antibiotic resistance in pediatric urology

    PubMed Central

    Copp, Hillary L.

    2014-01-01

    Antibiotics are a mainstay in the treatment of bacterial infections, though their use is a primary risk factor for the development of antibiotic resistance. Antibiotic resistance is a growing problem in pediatric urology as demonstrated by increased uropathogen resistance. Lack of urine testing, nonselective use of prophylaxis, and poor empiric prescribing practices exacerbate this problem. This article reviews antibiotic utilization in pediatric urology with emphasis on modifiable practice patterns to potentially help mitigate the growing rates of antibiotic resistance. This includes urine testing to only treat when indicated and tailor broad-spectrum therapy as able; selective application of antibiotic prophylaxis to patients with high-grade vesicoureteral reflux and hydronephrosis with counseling regarding the importance of compliance; and using local antiobiograms, particularly pediatric-specific antiobiograms, with inpatient versus outpatient data. PMID:24688601

  12. Antibiotic resistance in soil and water environments.

    PubMed

    Esiobu, Nwadiuto; Armenta, Lisa; Ike, Joseph

    2002-06-01

    Seven locations were screened for antibiotic-resistant bacteria using a modified agar dilution technique. Isolates resistant to high levels of antibiotics were screened for r plasmids. Low-level resistance (25 micro g x ml(-1)) was widespread for ampicillin, penicillin, tetracycline, vancomycin and streptomycin but not for kanamycin. Resistant populations dropped sharply at high antibiotic levels, suggesting that intrinsic non-emergent mechanisms were responsible for the multiple drug resistance exhibited at low doses. Dairy farm manure contained significantly (P < 0.01) more (%) resistant bacteria than the other sites. Bacteria isolated from a dairy water canal, a lake by a hospital and a residential garden (fertilized by farm manure) displayed resistance frequencies of 77, 75 and 70%, respectively. Incidence of tetracycline resistance was most prevalent at 47-89% of total bacteria. Out of 200 representative isolates analyzed, Pseudomonas, Enterococcus-like bacteria, Enterobacter and Burkholderia species constituted the dominant reservoirs of resistance at high drug levels (50-170 micro g x ml(-1)). Plasmids were detected in only 29% (58) of these bacteria with tetracycline resistance accounting for 65% of the plasmid pool. Overall, resistance trends correlated to the abundance and type of bacterial species present in the habitat. Environmental reservoirs of resistance include opportunistic pathogens and constitute some public health concern. PMID:12396530

  13. Combating Antibiotic Resistance

    MedlinePlus

    ... for infectious diseases. back to top Antibiotics Fight Bacteria, Not Viruses Antibiotics are meant to be used ... treat strep throat, which is caused by streptococcal bacteria, and skin infections caused by staphylococcal bacteria. Although ...

  14. 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.

  15. 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 ...

  16. 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

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

    PubMed

    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.

  18. Reservoirs of antibiotic resistance genes.

    PubMed

    Salyers, Abigail; Shoemaker, Nadja B

    2006-01-01

    A potential concern about the use of antibiotics in animal husbundary is that, as antibiotic resistant bacteria move from the farm into the human diet, they may pass antibiotic resistance genes to bacteria that normally reside in a the human intestinal tract and from there to bacteria that cause human disease (reservoir hypothesis). In this article various approaches to evaluating the risk of agricultural use of antibiotics are assessed critically. In addition, the potential benefits of applying new technology and using new insights from the field of microbial ecology are explained.

  19. [Evolution in the antibiotic susceptibility and resistance].

    PubMed

    Stefani, S

    2009-07-01

    Over the last decade the proliferation of antibiotic-resistant pathogens has been a growing problem, especially in some geographic areas, making useless most of the classical antibiotic therapies. The rapid emergence of resistant bacteria is the result of different factors as the intrinsic microbial complexity, the growing attitude to travel of humans, animals and goods, the use of antibiotics outside hospitals, and the lack of precise therapeutic chooses for high risk group of patients. The antibiotic-resistance becomes certainly a serious problem when a resistant pathogen, and often multi-resistant today, is present in an infective site. In fact in a recent estimate of the Centre for Disease Control and Prevention (CDC) about 90.000 deaths per year in the USA are attributable to bacterial infections and in particular to resistant pathogens. It appears clear that the clinic relevance of this problem is the decimation of the sensible germs of the normal flora that leads to the upper hand of the only resistant bacteria. The antibiotic therapy, in fact, select the resistance and each bacteria has developed a particular strategy to survive: mutations of the genetic content or acquisition of resistance genes from the external. Among the Gram positive bacteria, besides methicillin resistant Staphyloccocus aureus, there are other pathogens such as coagulase-negative staphylococci (CoNS), Enterococcus faecium and Enterococcus faecalis, some species of streptococci and multiresistant Corynebacterium. The CoNS, eg. S. epidermidis, S. hominis and S. haemolyticus, are recognized as new important nosocomial pathogens and are not only responsible of invasive infections but have become in few years resistant to oxacillin (more than 60%) and multiresistant. The unsuspected fragility of glycopeptides, which for 40 years have been the most important treatment against infections due to Gram-positive bacteria, has posed the need for new antimicrobial molecules. Among the therapeutic

  20. [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.

  1. Suppression of antibiotic resistance acquisition by combined use of antibiotics.

    PubMed

    Suzuki, Shingo; Horinouchi, Takaaki; Furusawa, Chikara

    2015-10-01

    We analyzed the effect of combinatorial use of antibiotics with a trade-off relationship of resistance, i.e., resistance acquisition to one drug causes susceptibility to the other drug, and vice versa, on the evolution of antibiotic resistance. We demonstrated that this combinatorial use of antibiotics significantly suppressed the acquisition of resistance.

  2. Antibiotic / Antimicrobial Resistance Glossary

    MedlinePlus

    ... on the Farm Get Smart About Antibiotics Week File Formats Help: How do I view different file formats (PDF, DOC, PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel ...

  3. 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.

  4. 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

  5. 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

  6. 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.

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

    PubMed

    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. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This review article proposes 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 ...

  10. 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...

  11. 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.

  12. 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. PMID:26999656

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

    PubMed

    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.

  14. 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

  15. Antibiotic Resistance Related to Biofilm Formation in Klebsiella pneumoniae.

    PubMed

    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.

  16. 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.

  17. 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

  18. Rationalizing antibiotic use to limit antibiotic resistance in India+

    PubMed Central

    2011-01-01

    Antibiotic resistance, a global concern, is particularly pressing in developing nations, including India, where the burden of infectious disease is high and healthcare spending is low. The Global Antibiotic Resistance Partnership (GARP) was established to develop actionable policy recommendations specifically relevant to low- and middle-income countries where suboptimal access to antibiotics - not a major concern in high-income countries - is possibly as severe a problem as is the spread of resistant organisms. This report summarizes the situation as it is known regarding antibiotic use and growing resistance in India and recommends short and long term actions. Recommendations aim at (i) reducing the need for antibiotics; (ii) lowering resistance-enhancing drug pressure through improved antibiotic targeting, and (iii) eliminating antibiotic use for growth promotion in agriculture. The highest priority needs to be given to (i) national surveillance of antibiotic resistance and antibiotic use - better information to underpin decisions on standard treatment guidelines, education and other actions, as well as to monitor changes over time; (ii) increasing the use of diagnostic tests, which necessitates behavioural changes and improvements in microbiology laboratory capacity; (iii) setting up and/or strengthening infection control committees in hospitals; and (iv) restricting the use of antibiotics for non-therapeutic uses in agriculture. These interventions should help to reduce the spread of antibiotic resistance, improve public health directly, benefit the populace and reduce pressure on the healthcare system. Finally, increasing the types and coverage of childhood vaccines offered by the government would reduce the disease burden enormously and spare antibiotics. PMID:21985810

  19. 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.

  20. Antibiotic resistance: a growing and multifaceted problem.

    PubMed

    Clark, L

    Antibiotic resistance is an increasing problem worldwide that is exacerbated by the overuse and misuse of antibiotics. Patients, pharmaceutical marketing, and the use of antibiotics in veterinary medicine and animal husbandry are important factors to consider in the emergence of resistance. Infection control measures to prevent the spread of antibiotic-resistant bacteria are compromised by poor compliance to basic measures such as handwashing and standards of environmental cleanliness. Wider epidemiological factors such as global travel and complacency towards public health must also be considered. This article aims to improve understanding of antibiotic resistance and suggests ways in which nurses can contribute towards the strategy to address the problem.

  1. Overcoming Resistance to β-Lactam Antibiotics

    PubMed Central

    Worthington, Roberta J.; Melander, Christian

    2013-01-01

    β-Lactam antibiotics are one of the most important antibiotic classes but are plagued by problems of resistance and the development of new β-lactam antibiotics through side chain modification of existing β-lactam classes is not keeping pace with resistance development. In this perspective we summarize small molecule strategies to overcome resistance to β-lactam antibiotics. These approaches include the development of β-lactamase inhibitors and compounds that interfere with the ability of the bacteria to sense an antibiotic threat and activate their resistance mechanisms. PMID:23530949

  2. 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.

  3. 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

  4. 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

  5. Antibiotic overuse and resistance in dermatology.

    PubMed

    Chon, Susan Y; Doan, Hung Q; Mays, Rana Majd; Singh, Selina M; Gordon, Rachel A; Tyring, Stephen K

    2012-01-01

    Antibiotics have a significant role in dermatology, treating a wide range of diseases, including acne, rosacea, inflammatory skin conditions and skin structure infections, such as cellulitis, folliculitis, carbuncles, and furuncles. Because of their consistent use, utility, and availability, antibiotics are susceptible to overuse within the medical practice, and, specific to this discussion, in the dermatologic setting. The issue of continuously increasing risk of antibiotic resistance remains an important concern to the dermatologist. The scope of this review will be to provide an overview of the common antibiotics used in the dermatologic setting with an emphasis on identifying areas of overuse, reported bacterial resistance, and discussion of clinical management aimed at decreasing antibiotic resistance.

  6. Antibiotics and antibiotic resistance: a bitter fight against evolution.

    PubMed

    Rodríguez-Rojas, Alexandro; Rodríguez-Beltrán, Jerónimo; Couce, Alejandro; Blázquez, Jesús

    2013-08-01

    One of the most terrible consequences of Darwinian evolution is arguably the emergence and spread of antibiotic resistance, which is becoming a serious menace to modern societies. While spontaneous mutation, recombination and horizontal gene transfer are recognized as the main causes of this notorious phenomenon; recent research has raised awareness that sub-lethal concentrations of antibiotics can also foster resistance as an undesirable side-effect. They can produce genetic changes by different ways, including a raise of free radicals within the cell, induction of error-prone DNA-polymerases mediated by SOS response, imbalanced nucleotide metabolism or affect directly DNA. In addition to certain environmental conditions, subinhibitory concentrations of antimicrobials may increase, even more, the mutagenic effect of antibiotics. Here, we review the state of knowledge on antibiotics as promoters of antibiotic resistance.

  7. 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.

  8. 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. PMID:25817583

  9. General principles of antibiotic resistance in bacteria.

    PubMed

    Martinez, Jose L

    2014-03-01

    Given the impact of antibiotic resistance on human health, its study is of great interest from a clinical view- point. In addition, antibiotic resistance is one of the few examples of evolution that can be studied in real time. Knowing the general principles involved in the acquisition of antibiotic resistance is therefore of interest to clinicians, evolutionary biologists and ecologists. The origin of antibiotic resistance genes now possessed by human pathogens can be traced back to environmental microorganisms. Consequently, a full understanding of the evolution of antibiotic resistance requires the study of natural environments as well as clinical ecosystems. Updated information on the evolutionary mechanisms behind resistance, indicates that ecological connectivity, founder effect and fitness costs are important bottle- necks that modulate the transfer of resistance from environmental microorganisms to pathogens. PMID:24847651

  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. 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

  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. 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...

  15. Outer Membrane Permeability and Antibiotic Resistance

    PubMed Central

    Delcour, Anne H.

    2009-01-01

    Summary To date most antibiotics are targeted at intracellular processes, and must be able to penetrate the bacterial cell envelope. In particular, the outer membrane of Gram-negative bacteria provides a formidable barrier that must be overcome. There are essentially two pathways that antibiotics can take through the outer membrane: a lipid-mediated pathway for hydrophobic antibiotics, and general diffusion porins for hydrophilic antibiotics. The lipid and protein compositions of the outer membrane have a strong impact on the sensitivity of bacteria to many types of antibiotics, and drug resistance involving modifications of these macromolecules is common. This review will describe the molecular mechanisms for permeation of antibiotics through the outer membrane, and the strategies that bacteria have deployed to resist antibiotics by modifications of these pathways. PMID:19100346

  16. Syphilis: antibiotic treatment and resistance.

    PubMed

    Stamm, L V

    2015-06-01

    Syphilis is a chronic, multi-stage infectious disease that is usually transmitted sexually by contact with an active lesion of a partner or congenitally from an infected pregnant woman to her fetus. Although syphilis is still endemic in many developing countries, it has re-emerged in several developed countries. The resurgence of syphilis is a major concern to global public health, particularly since the lesions of early syphilis increase the risk of acquisition and transmission of infection with human immunodeficiency virus (HIV). Because there is no vaccine to prevent syphilis, control is mainly dependent on the identification and treatment of infected individuals and their contacts with penicillin G, the first-line drug for all stages of syphilis. The emergence of clinically significant azithromycin resistance in Treponema pallidum subsp. pallidum, the syphilis agent, has resulted in treatment failures, thus precluding the routine use of this second-line drug. Information is presented here on the diagnosis and recommended antibiotic treatment of syphilis and the challenge of macrolide-resistant T. pallidum.

  17. [Antibiotic resistance--bacteria fight back].

    PubMed

    Tambić Andrasević, Arjana

    2004-01-01

    Antibiotic resistance has become one of the leading problems in modern medicine. Resistance to antibiotics emerges in bacteria due to genetic mutations and consecutive selection of resistant mutants through selective pressure of antibiotics present in large amounts in soil, plants, animals and humans. Exchange of genetic material coding for resistance is possible even between unrelated organisms and further promotes the spread of resistance. Constantly evolving resistance mechanisms force experts to redefine breakpoint concentrations and interpretation of in vitro antibiotic sensitivity testing. Developing new antimicrobial agents does not seem to be enough to keep up pace with ever changing bacteria. Using antibiotics prudently and developing new approaches to the treatment of infections is vital for the future. The European Antimicrobial Resistance Surveillance System (EARSS) data clearly show that Scandinavian countries and The Netherlands have the lowest rates of resistance, while Southern and Eastern European countries have the highest prevalence of resistance. This is linked to the European Surveillance of Antimicrobial Consumption (ESAC) data that show very low consumption of antibiotics in Scandinavian countries and The Netherlands. Compliance with strict infection control policies related to multidrug resistant organisms is also high in these countries. Although it is important to be aware of the resistance problems worldwide, rational use of antibiotics should be based on the knowledge of local resistance patterns in common pathogens. Since 1996 there is a continuous surveillance of resistance in Croatia through the Croatian Committee for Antibiotic Resistance Surveillance. There is a particular concern about the rising penicillin and macrolide resistance in pneumococci. In Croatia, data for 2002 suggest that resistance to penicillin in pneumococci was 30% (low level) and 2% (high level). Among invasive isolates, 19% had reduced susceptibility to

  18. Antibiotic-Resistant Bacteria Detected in Sewage Spill

    MedlinePlus

    ... animals -- the more the antibiotic resistant organisms and antibiotic resistance genes can enter the environment and contribute to the spread of antibiotic resistance, especially for those drugs considered the 'last resort' ...

  19. [Modification of antibiotic resistance in microbial symbiosis].

    PubMed

    Aznabaeva, L M; Usviatsov, B Ia; Bukharin, O V

    2010-01-01

    In antibiotic therapy it is necessary to use drugs active against the pathogen in its association with the host normal microflora. The aim of the study was to investigate modification of antibiotic resistance under conditions of the pathogen association with the representatives of the host normal microflora and to develop the microbiological criteria for determining effectiveness of antibacterials. Modification of microbial antibiotic resistance was investigated in 408 associations. Various changes in the antibiotic resistance of the strains were revealed: synergism, antagonism and indifference. On the basis of the results it was concluded that in the choice of the antibiotic active against Staphylococcus aureus and Streptococcus pyogenes the preference should be given to oxacillin, gentamicin and levomycetin, since the resistance of the pathogens to these antibiotics under the association conditions did not increase, which could contribute to their destruction, whereas the resistance of the normoflora increased or did not change, which was important for its retention in the biocenosis. The data on changeability of the antibiotic resistance of the microbial strains under the association conditions made it possible to develop microbiological criteria for determining effectiveness of antibiotics in the treatment of inflammatory diseases of microbial etiology (RF Patent No. 2231554). PMID:21033469

  20. Multiple antibiotic resistance in Rhizobium japonicum.

    PubMed

    Cole, M A; Elkan, G H

    1979-05-01

    A total of 48 strains of the soil bacterium Rhizobium japonicum were screened for their response to several widely used antibiotics. Over 60% of the strains were resistant to chloramphenicol, polymyxin B, and erythromycin, and 47% or more of the strains were resistant to neomycin and penicillin G, when tested by disk assay procedures. The most common grouping of resistances in strains was simultaneous resistance to tetracycline, penicillin G, neomycin, chloramphenicol, and streptomycin (25% of all strains tested). The occurrence of multiple drug resistance in a soil bacterium that is not a vertebrate pathogen suggests that chemotherapeutic use of antibiotics is not required for the development of multiple drug resistance. PMID:485137

  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. 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. PMID:26563691

  3. Coping with antibiotic resistance: contributions from genomics

    PubMed Central

    2010-01-01

    Antibiotic resistance is a public health issue of global dimensions with a significant impact on morbidity, mortality and healthcare-associated costs. The problem has recently been worsened by the steady increase in multiresistant strains and by the restriction of antibiotic discovery and development programs. Recent advances in the field of bacterial genomics will further current knowledge on antibiotic resistance and help to tackle the problem. Bacterial genomics and transcriptomics can inform our understanding of resistance mechanisms, and comparative genomic analysis can provide relevant information on the evolution of resistant strains and on resistance genes and cognate genetic elements. Moreover, bacterial genomics, including functional and structural genomics, is also proving to be instrumental in the identification of new targets, which is a crucial step in new antibiotic discovery programs. PMID:20236502

  4. 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

  5. Overview: Global and Local Impact of Antibiotic Resistance.

    PubMed

    Watkins, Richard R; Bonomo, Robert A

    2016-06-01

    The rapid and ongoing spread of antibiotic resistance poses a serious threat to global public health. The indiscriminant use of antibiotics in agriculture and human medicine along with increasingly connected societies has fueled the distribution of antibiotic-resistant bacteria. These factors together have led to rising numbers of infections caused by multidrug-resistant and pan-resistant bacteria, with increases in morbidity and mortality. This article summarizes the trends in antibiotic resistance, discusses the impact of antibiotic resistance on society, and reviews the use of antibiotics in agriculture. Feasible ways to tackle antibiotic resistance to avert a post-antibiotic era are suggested.

  6. 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

  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. 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...

  9. 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. PMID:25450262

  10. 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.

  11. Methicillin-resistant Staphylococcus aureus antibiotic resistance and virulence.

    PubMed

    Xia, Jufeng; Gao, Jianjun; Kokudo, Norihiro; Hasegawa, Kiyoshi; Tang, Wei

    2013-06-01

    Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most critical causes of healthcare-related or community-related infections. Resistance to most β-lactam antibiotics makes MRSA a big threat to clinical treatment. Utilization of low efficiency antibiotics such as vancomycin and teicoplanin makes new choices for therapies. Recently, much researchhas shed light on relevance between genetic mutations of MRSA and clinical characteristics such as antibiotic resistance, and virulence. These findings could contribute to development of novel antibiotics and vaccines.

  12. 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

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

    PubMed

    Tazzyman, Samuel J; Hall, Alex R

    2015-04-01

    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.

  14. 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'. PMID:22534508

  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. Emergence of antibiotic-resistant extremophiles (AREs).

    PubMed

    Gabani, Prashant; Prakash, Dhan; Singh, Om V

    2012-09-01

    Excessive use of antibiotics in recent years has produced bacteria that are resistant to a wide array of antibiotics. Several genetic and non-genetic elements allow microorganisms to adapt and thrive under harsh environmental conditions such as lethal doses of antibiotics. We attempt to classify these microorganisms as antibiotic-resistant extremophiles (AREs). AREs develop strategies to gain greater resistance to antibiotics via accumulation of multiple genes or plasmids that harbor genes for multiple drug resistance (MDR). In addition to their altered expression of multiple genes, AREs also survive by producing enzymes such as penicillinase that inactivate antibiotics. It is of interest to identify the underlying molecular mechanisms by which the AREs are able to survive in the presence of wide arrays of high-dosage antibiotics. Technologically, "omics"-based approaches such as genomics have revealed a wide array of genes differentially expressed in AREs. Proteomics studies with 2DE, MALDI-TOF, and MS/MS have identified specific proteins, enzymes, and pumps that function in the adaptation mechanisms of AREs. This article discusses the molecular mechanisms by which microorganisms develop into AREs and how "omics" approaches can identify the genetic elements of these adaptation mechanisms. These objectives will assist the development of strategies and potential therapeutics to treat outbreaks of pathogenic microorganisms in the future.

  17. RAC: Repository of Antibiotic resistance Cassettes

    PubMed Central

    Tsafnat, Guy; Copty, Joseph; Partridge, Sally R.

    2011-01-01

    Antibiotic resistance in bacteria is often due to acquisition of resistance genes associated with different mobile genetic elements. In Gram-negative bacteria, many resistance genes are found as part of small mobile genetic elements called gene cassettes, generally found integrated into larger elements called integrons. Integrons carrying antibiotic resistance gene cassettes are often associated with mobile elements and here are designated ‘mobile resistance integrons’ (MRIs). More than one cassette can be inserted in the same integron to create arrays that contribute to the spread of multi-resistance. In many sequences in databases such as GenBank, only the genes within cassettes, rather than whole cassettes, are annotated and the same gene/cassette may be given different names in different entries, hampering analysis. We have developed the Repository of Antibiotic resistance Cassettes (RAC) website to provide an archive of gene cassettes that includes alternative gene names from multiple nomenclature systems and allows the community to contribute new cassettes. RAC also offers an additional function that allows users to submit sequences containing cassettes or arrays for annotation using the automatic annotation system Attacca. Attacca recognizes features (gene cassettes, integron regions) and identifies cassette arrays as patterns of features and can also distinguish minor cassette variants that may encode different resistance phenotypes (aacA4 cassettes and bla cassettes-encoding β-lactamases). Gaps in annotations are manually reviewed and those found to correspond to novel cassettes are assigned unique names. While there are other websites dedicated to integrons or antibiotic resistance genes, none includes a complete list of antibiotic resistance gene cassettes in MRI or offers consistent annotation and appropriate naming of all of these cassettes in submitted sequences. RAC thus provides a unique resource for researchers, which should reduce confusion

  18. 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

  19. Antibiotic resistance mechanisms of Myroides sp.

    PubMed

    Hu, Shao-hua; Yuan, Shu-xing; Qu, Hai; Jiang, Tao; Zhou, Ya-jun; Wang, Ming-xi; Ming, De-song

    2016-03-01

    Bacteria of the genus Myroides (Myroides spp.) are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the resistance mechanisms are not fully elucidated. Current strain identification methods based on biochemical traits are unable to identify strains accurately at the species level. While 16S ribosomal RNA (rRNA) gene sequencing can accurately achieve this, it fails to give information on the status and mechanisms of antibiotic resistance, because the 16S rRNA sequence contains no information on resistance genes, resistance islands or enzymes. We hypothesized that obtaining the whole genome sequence of Myroides sp., using next generation sequencing methods, would help to clarify the mechanisms of pathogenesis and antibiotic resistance, and guide antibiotic selection to treat Myroides sp. infections. As Myroides sp. can survive in hospitals and the environment, there is a risk of nosocomial infections and pandemics. For better management of Myroides sp. infections, it is imperative to apply next generation sequencing technologies to clarify the antibiotic resistance mechanisms in these bacteria.

  20. Antibiotic resistance mechanisms of Myroides sp.*

    PubMed Central

    Hu, Shao-hua; Yuan, Shu-xing; Qu, Hai; Jiang, Tao; Zhou, Ya-jun; Wang, Ming-xi; Ming, De-song

    2016-01-01

    Bacteria of the genus Myroides (Myroides spp.) are rare opportunistic pathogens. Myroides sp. infections have been reported mainly in China. Myroides sp. is highly resistant to most available antibiotics, but the resistance mechanisms are not fully elucidated. Current strain identification methods based on biochemical traits are unable to identify strains accurately at the species level. While 16S ribosomal RNA (rRNA) gene sequencing can accurately achieve this, it fails to give information on the status and mechanisms of antibiotic resistance, because the 16S rRNA sequence contains no information on resistance genes, resistance islands or enzymes. We hypothesized that obtaining the whole genome sequence of Myroides sp., using next generation sequencing methods, would help to clarify the mechanisms of pathogenesis and antibiotic resistance, and guide antibiotic selection to treat Myroides sp. infections. As Myroides sp. can survive in hospitals and the environment, there is a risk of nosocomial infections and pandemics. For better management of Myroides sp. infections, it is imperative to apply next generation sequencing technologies to clarify the antibiotic resistance mechanisms in these bacteria. PMID:26984839

  1. 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.

  2. Plasmid encoded antibiotic resistance: acquisition and transfer of antibiotic resistance genes in bacteria

    PubMed Central

    Bennett, P M

    2008-01-01

    Bacteria have existed on Earth for three billion years or so and have become adept at protecting themselves against toxic chemicals. Antibiotics have been in clinical use for a little more than 6 decades. That antibiotic resistance is now a major clinical problem all over the world attests to the success and speed of bacterial adaptation. Mechanisms of antibiotic resistance in bacteria are varied and include target protection, target substitution, antibiotic detoxification and block of intracellular antibiotic accumulation. Acquisition of genes needed to elaborate the various mechanisms is greatly aided by a variety of promiscuous gene transfer systems, such as bacterial conjugative plasmids, transposable elements and integron systems, that move genes from one DNA system to another and from one bacterial cell to another, not necessarily one related to the gene donor. Bacterial plasmids serve as the scaffold on which are assembled arrays of antibiotic resistance genes, by transposition (transposable elements and ISCR mediated transposition) and site-specific recombination mechanisms (integron gene cassettes). The evidence suggests that antibiotic resistance genes in human bacterial pathogens originate from a multitude of bacterial sources, indicating that the genomes of all bacteria can be considered as a single global gene pool into which most, if not all, bacteria can dip for genes necessary for survival. In terms of antibiotic resistance, plasmids serve a central role, as the vehicles for resistance gene capture and their subsequent dissemination. These various aspects of bacterial resistance to antibiotics will be explored in this presentation. PMID:18193080

  3. Antibiotic resistance of gram-negative bacteria in rivers, United States.

    PubMed

    Ash, Ronald J; Mauck, Brena; Morgan, Melissa

    2002-07-01

    Bacteria with intrinsic resistance to antibiotics are found in nature. Such organisms may acquire additional resistance genes from bacteria introduced into soil or water, and the resident bacteria may be the reservoir or source of widespread resistant organisms found in many environments. We isolated antibiotic-resistant bacteria in freshwater samples from 16 U.S. rivers at 22 sites and measured the prevalence of organisms resistant to beta-lactam and non-beta-lactam antibiotics. Over 40% of the bacteria resistant to more than one antibiotic had at least one plasmid. Ampicillin resistance genes, as well as other resistance traits, were identified in 70% of the plasmids. The most common resistant organisms belonged to the following genera: Acinetobacter, Alcaligenes, Citrobacter, Enterobacter, Pseudomonas, and Serratia. PMID:12095440

  4. [Antibiotic resistance of bacteria Campylobacter sp].

    PubMed

    Rzewuska, Katarzyna; Korsak, Dorota; Maćkiw, Elzbieta

    2010-01-01

    Campylobacter is recognized as a major cause of human acute bacterial enteritis. The incidence of human Campylobacter infection has increased markedly in both developed and developing countries and, more significantly, so has rapid emergence of antibiotic-resistant Campylobacter strains. It is caused by improper applying antibiotics in treating people and too frequent applying these substances in the animal husbandry. In this review, the patterns of emerging resistance to the antimicrobial agents useful in treatment of the disease are presented and the mechanisms of resistance to these drugs in Campylobacter spp. are discussed.

  5. Rapid Antibiotic Resistance Evolution of GASP Mutants

    NASA Astrophysics Data System (ADS)

    Zhang, Qiucen; Kim, Hyunsung; Pourmand, Nader; Austin, Robert

    2012-02-01

    The GASP phenotype in bacteria is due to a mutation which enables the bacteria to grow under high stress conditions where other bacteria stop growing. We probe using our Death Galaxy microenvironment how rapidly the GASP mutant can evolve resistance to mutagenic antibiotics compared to wild-type bacteria, and explore the genomic landscape changes due to the evolution of resistance.

  6. 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

  7. Antibiotic-resistant vibrios in farmed shrimp.

    PubMed

    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.

  8. Characterization of antibiotic-resistance genes in antibiotic resistance Escherichia coli isolates from a lake.

    PubMed

    Wang, Chao; Gu, Xiucong; Zhang, Songhe; Wang, Peifang; Guo, Chuan; Gu, Ju; Hou, Jun

    2013-11-01

    The spread of antibiotic-resistance bacteria and antibiotic-resistance genes (ARGs) has been of concern worldwide. In this study, 114 Escherichia coli isolates were isolated from surface water samples of a lake to identify their susceptibility to antibiotics, including tetracycline (TC), gentamicin (GN), ampicillin (AMP), streptomycin (ST), oxytetracycline (OC), levofloxacin (LEV), nalidixic acid (NA), and sulfamethoxazole/trimethoprim (SFT). Isolates showing resistance to TC, GN, AMP, ST, OC, LEV, NA, and SFT occurred in 50, 76, 68, 71, 55, 32, 82, and 85 % of the total isolates, respectively. Thirty-seven different resistance patterns were identified, and the most abundant resistance profile (28 of 104) was TC/GN/AMP/ST/OC/LEV/NA/SFT. The occurrence of 29 ARGs were detected in their corresponding resistance clones, and 88 % of TC-resistance, 94 % of SFT-resistance, 90 % of AMP-resistance, 78 % of ST-resistance, and 72 % of quinolone-resistance clones can be described by their corresponding ARGs. It should be noted that most of these antibiotic-resistance clones harbored at least two corresponding ARGs, indicating that high frequencies of combined ARGs occurred in these isolates. In addition, 9 new types of DNA sequence of qnr(B) gene were obtained and were clustered into the same group as showed by phylogenetic trees analysis. These results suggest that the development of antibiotic resistance can be ascribed to the high frequency in the recombination of ARGs through horizontal gene transfer.

  9. 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. PMID:23183460

  10. 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.

  11. The food safety perspective of antibiotic resistance.

    PubMed

    McDermott, P F; Zhao, S; Wagner, D D; Simjee, S; Walker, R D; White, D G

    2002-05-01

    Bacterial antimicrobial resistance in both the medical and agricultural fields has become a serious problem worldwide. Antibiotic resistant strains of bacteria are an increasing threat to animal and human health, with resistance mechanisms having been identified and described for all known antimicrobials currently available for clinical use. There is currently increased public and scientific interest regarding the administration of therapeutic and sub-therapeutic antimicrobials to animals, due primarily to the emergence and dissemination of multiple antibiotic resistant zoonotic bacterial pathogens. This issue has been the subject of heated debates for many years, however, there is still no complete consensus on the significance of antimicrobial use in animals, or resistance in bacterial isolates from animals, on the development and dissemination of antibiotic resistance among human bacterial pathogens. In fact, the debate regarding antimicrobial use in animals and subsequent human health implications has been going on for over 30 years, beginning with the release of the Swann report in the United Kingdom. The latest report released by the National Research Council (1998) confirmed that there were substantial information gaps that contribute to the difficulty of assessing potential detrimental effects of antimicrobials in food animals on human health. Regardless of the controversy, bacterial pathogens of animal and human origin are becoming increasingly resistant to most frontline antimicrobials, including expanded-spectrum cephalosporins, aminoglycosides, and even fluoroquinolones. The lion's share of these antimicrobial resistant phenotypes is gained from extra-chromosomal genes that may impart resistance to an entire antimicrobial class. In recent years, a number of these resistance genes have been associated with large, transferable, extra-chromosomal DNA elements, called plasmids, on which may be other DNA mobile elements, such as transposons and integrons

  12. Antibiotic resistance of bacterial litter isolates.

    PubMed

    Kelley, T R; Pancorbo, O C; Merka, W C; Barnhart, H M

    1998-02-01

    Use of antibiotics in subtherapeutic doses as growth-promoting feed additives for animal production is widespread in the U.S. and throughout the world. Previous studies by our research group concluded that size fractionation of poultry (broiler) litter followed by storage facilitated reutilization of litter as a soil amendment or bedding supplement. However, litter microbial contamination, including antibiotic-resistant populations, and accumulation of metals and other elements may limit litter reutilization. Litter from four broiler houses was separated into a fine fraction for use as a soil amendment, and a coarse fraction for reutilization as a bedding supplement in growing subsequent flocks of broilers. Fractions and whole litter were stored in indoor piles simulating farm storage conditions for 4 mo with periodic analysis for metals, other elements, and culturable bacteria (including total and fecal coliform, Aeromonas hydrophila, Pseudomonas aeruginosa, Yersinia enterocolitica, and Campylobacter jejuni). Representative bacterial isolates were tested for their sensitivity to 12 common antibiotics (ampicillin, bacitracin, cephalothin, erythromycin, gentamicin, kanamycin, nalidixic acid, neomycin, penicillin, streptomycin, sulfisoxazole, and tetracycline) using the Kirby-Bauer technique. Pathogens and indicator bacteria tested were found to be resistant to multiple antibiotics. Data suggest that microbial contamination of litter should be reduced or eliminated prior to reutilization to minimize environmental health risks related to transfer of antibiotic-resistant bacteria to humans or other animals. PMID:9495488

  13. The expression of antibiotic resistance genes in antibiotic-producing bacteria.

    PubMed

    Mak, Stefanie; Xu, Ye; Nodwell, Justin R

    2014-08-01

    Antibiotic-producing bacteria encode antibiotic resistance genes that protect them from the biologically active molecules that they produce. The expression of these genes needs to occur in a timely manner: either in advance of or concomitantly with biosynthesis. It appears that there have been at least two general solutions to this problem. In many cases, the expression of resistance genes is tightly linked to that of antibiotic biosynthetic genes. In others, the resistance genes can be induced by their cognate antibiotics or by intermediate molecules from their biosynthetic pathways. The regulatory mechanisms that couple resistance to antibiotic biosynthesis are mechanistically diverse and potentially relevant to the origins of clinical antibiotic resistance.

  14. Antibiotic resistance genes in water environment.

    PubMed

    Zhang, Xu-Xiang; Zhang, Tong; Fang, Herbert H P

    2009-03-01

    The use of antibiotics may accelerate the development of antibiotic resistance genes (ARGs) and bacteria which shade health risks to humans and animals. The emerging of ARGs in the water environment is becoming an increasing worldwide concern. Hundreds of various ARGs encoding resistance to a broad range of antibiotics have been found in microorganisms distributed not only in hospital wastewaters and animal production wastewaters, but also in sewage, wastewater treatment plants, surface water, groundwater, and even in drinking water. This review summarizes recently published information on the types, distributions, and horizontal transfer of ARGs in various aquatic environments, as well as the molecular methods used to detect environmental ARGs, including specific and multiplex PCR (polymerase chain reaction), real-time PCR, DNA sequencing, and hybridization based techniques. PMID:19130050

  15. Combination of essential oils and antibiotics reduce antibiotic resistance in plasmid-conferred multidrug resistant bacteria.

    PubMed

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

    2013-06-15

    In this study we investigated the relationship between several selected commercially available essential oils and beta-lactam antibiotics on their antibacterial effect against multidrug resistant bacteria. The antibacterial activity of essential oils and antibiotics was assessed using broth microdilution. The combined effects between essential oils of cinnamon bark, lavender, marjoram, tea tree, peppermint and ampicillin, piperacillin, cefazolin, cefuroxime, carbenicillin, ceftazidime, meropenem, were evaluated by means of the checkerboard method against beta-lactamase-producing Escherichia coli. In the latter assays, fractional inhibitory concentration (FIC) values were calculated to characterize interaction between the combinations. Substantial susceptibility of the bacteria toward natural antibiotics and a considerable reduction in the minimum inhibitory concentrations (MIC) of the antibiotics were noted in some paired combinations of antibiotics and essential oils. Out of 35 antibiotic-essential oil pairs tested, four of them showed synergistic effect (FIC≤0.5) and 31 pairs showed no interaction (FIC>0.5-4.0). The preliminary results obtained highlighted the occurrence of a pronounced synergistic relationship between piperacillin/cinnamon bark oil, piperacillin/lavender oil, piperacillin/peppermint oil as well as meropenem/peppermint oil against two of the three bacteria under study with a FIC index in the range 0.26-0.5. The finding highlighted the potential of peppermint, cinnamon bark and lavender essential oils being as antibiotic resistance modifying agent. Reduced usage of antibiotics could be employed as a treatment strategy to decrease the adverse effects and possibly to reverse the beta-lactam antibiotic resistance.

  16. NOTE: Dielectrophoretic assay of bacterial resistance to antibiotics

    NASA Astrophysics Data System (ADS)

    Johari, Juliana; Hübner, Yvonne; Hull, Judith C.; Dale, Jeremy W.; Hughes, Michael P.

    2003-07-01

    The dielectrophoretic collection spectra of antibiotic-sensitive and antibiotic-resistant strains of Staphylococcus epidermidis have been determined. These indicate that in the absence of antibiotic treatment there is a strong similarity between the dielectric properties of sensitive and resistant strains, and that there is a significant difference between the sensitive strains before and after treatment with the antibiotic streptomycin after 24 h exposure. This method offers possibilities for the assessment of bacterial resistance to antibiotics.

  17. 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

    2016-01-01

    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

  18. 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.

  19. 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

    2016-01-01

    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.

  20. 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

  1. 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 ...

  2. Helicobacter pylori uptake and efflux: basis for intrinsic susceptibility to antibiotics in vitro.

    PubMed

    Bina, J E; Alm, R A; Uria-Nickelsen, M; Thomas, S R; Trust, T J; Hancock, R E

    2000-02-01

    We previously demonstrated (M. M. Exner, P. Doig, T. J. Trust, and R. E. W. Hancock, Infect. Immun. 63:1567-1572, 1995) that Helicobacter pylori has at least one nonspecific porin, HopE, which has a low abundance in the outer membrane but forms large channels. H. pylori is relatively susceptible to most antimicrobial agents but less susceptible to the polycationic antibiotic polymyxin B. We demonstrate here that H. pylori is able to take up higher basal levels of the hydrophobic fluorescent probe 1-N-phenylnaphthylamine (NPN) than Pseudomonas aeruginosa or Escherichia coli, consistent with its enhanced susceptibility to hydrophobic agents. Addition of polymyxin B led to a further increase in NPN uptake, indicative of a self-promoted uptake pathway, but it required a much higher amount of polymyxin B to yield a 50% increase in NPN uptake in H. pylori (6 to 8 microg/ml) than in P. aeruginosa or E. coli (0.3 to 0.5 microg/ml), suggesting that H. pylori has a less efficient self-promoted uptake pathway. Since intrinsic resistance involves the collaboration of restricted outer membrane permeability and secondary defense mechanisms, such as periplasmic beta-lactamase (which H. pylori lacks) or efflux, we examined the possible role of efflux in antibiotic susceptibility. We had previously identified in H. pylori 11637 the presence of portions of three genes with homology to potential restriction-nodulation-division (RND) efflux systems. It was confirmed that H. pylori contained only these three putative RND efflux systems, named here hefABC, hefDEF, and hefGHI, and that the hefGHI system was expressed only in vivo while the two other RND systems were expressed both in vivo and in vitro. In uptake studies, there was no observable energy-dependent tetracycline, chloramphenicol, or NPN efflux activity in H. pylori. Independent mutagenesis of the three putative RND efflux operons in the chromosome of H. pylori had no effect on the in vitro susceptibility of H. pylori to 19

  3. Antibiotic resistance gene discovery in food-producing animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous environmental reservoirs contribute to the widespread antibiotic resistance problem in human pathogens. One environmental reservoir of particular importance is the intestinal bacteria of food-producing animals. In this review I examine recent discoveries of antibiotic resistance genes in ...

  4. 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.

  5. 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. PMID:26493767

  6. 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.

  7. Study of Antibiotic Resistance Pattern in Methicillin Resistant Staphylococcus Aureus with Special Reference to Newer Antibiotic

    PubMed Central

    Kaur, Dardi Charan; Chate, Sadhana Sanjay

    2015-01-01

    The worldwide epidemic of antibiotic resistance is in danger of ending the golden age of antibiotic therapy. Resistance impacts on all areas of medicine, and is making successful empirical therapy much more difficult to achieve. Staphylococcus aureus demonstrates a unique ability to quickly respond to each new antibiotic with the development of a resistance mechanism, starting with penicillin, until the most recent, linezolid and daptomycin. Methicillin resistant S. aureus (MRSA) has become endemic today in hospitals worldwide. Resistance to the newer antimicrobial-agents — linezolid, vancomycin, teicoplanin, and daptomycin are been reported and also the fear of pandrug-resistance. This study was carried out to know the antimicrobial resistant pattern of MRSA to newer antibiotic, to know any isolates are extensively-drug resistant (XDR)/pandrug resistant (PDR), inducible macrolide-lincosamide streptogramin B (iMLSB), and mupirocin resistance. Thirty-six MRSA isolates resistant to the routinely tested antibiotic were further tested for list of antibiotic by a group of international experts. Isolates were tested for iMLSB and mupirocin resistance by the disk diffusion method. Of 385 MRSA, 36 (9.35%) isolates of MRSA were resistant to the routinely tested antibiotic. Among these 36 MRSA isolates, none of our isolates were XDR/PDR or showed resistant to anti-MRSA cephalosporins (ceftaroline), phosphonic acids, glycopeptides, glycylcyclines, and fucidanes. Lower resistance was seen in oxazolidinones (2.78%), streptogramins (5.56%), lipopeptide (5.56%). Thirty-four (94.44%) isolates showed constitutive MLSB (cMLSB) resistance and two (5.56%) iMLSB phenotypes. High- and low-level mupirocin resistance were seen in 13 (36.11%) and six (16.67%), respectively. In our study, none of our isolates were XDR or PDR. No resistance was observed to ceftaroline, telavancin, teicoplanin, and vancomycin; but the presence of linezolid resistance (1, 2.28%) and daptomycin resistance (2

  8. Friend turned foe: evolution of enterococcal virulence and antibiotic resistance.

    PubMed

    Van Tyne, Daria; Gilmore, Michael S

    2014-01-01

    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.

  9. 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

  10. Friend turned foe: evolution of enterococcal virulence and antibiotic resistance.

    PubMed

    Van Tyne, Daria; Gilmore, Michael S

    2014-01-01

    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

  11. [The international surveillance of antibiotics resistance].

    PubMed

    Frimodt-Møller, Niels

    2011-11-01

    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. PMID:22053806

  12. 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.

  13. Fate of antibiotic resistant bacteria and genes during wastewater chlorination: implication for antibiotic resistance control.

    PubMed

    Yuan, Qing-Bin; Guo, Mei-Ting; Yang, Jian

    2015-01-01

    This study investigated fates of nine antibiotic-resistant bacteria as well as two series of antibiotic resistance genes in wastewater treated by various doses of chlorine (0, 15, 30, 60, 150 and 300 mg Cl2 min/L). The results indicated that chlorination was effective in inactivating antibiotic-resistant bacteria. Most bacteria were inactivated completely at the lowest dose (15 mg Cl2 min/L). By comparison, sulfadiazine- and erythromycin-resistant bacteria exhibited tolerance to low chlorine dose (up to 60 mg Cl2 min/L). However, quantitative real-time PCRs revealed that chlorination decreased limited erythromycin or tetracycline resistance genes, with the removal levels of overall erythromycin and tetracycline resistance genes at 0.42 ± 0.12 log and 0.10 ± 0.02 log, respectively. About 40% of erythromycin-resistance genes and 80% of tetracycline resistance genes could not be removed by chlorination. Chlorination was considered not effective in controlling antimicrobial resistance. More concern needs to be paid to the potential risk of antibiotic resistance genes in the wastewater after chlorination.

  14. Fate of Antibiotic Resistant Bacteria and Genes during Wastewater Chlorination: Implication for Antibiotic Resistance Control

    PubMed Central

    Yuan, Qing-Bin; Guo, Mei-Ting; Yang, Jian

    2015-01-01

    This study investigated fates of nine antibiotic-resistant bacteria as well as two series of antibiotic resistance genes in wastewater treated by various doses of chlorine (0, 15, 30, 60, 150 and 300 mg Cl2 min/L). The results indicated that chlorination was effective in inactivating antibiotic-resistant bacteria. Most bacteria were inactivated completely at the lowest dose (15 mg Cl2 min/L). By comparison, sulfadiazine- and erythromycin-resistant bacteria exhibited tolerance to low chlorine dose (up to 60 mg Cl2 min/L). However, quantitative real-time PCRs revealed that chlorination decreased limited erythromycin or tetracycline resistance genes, with the removal levels of overall erythromycin and tetracycline resistance genes at 0.42 ± 0.12 log and 0.10 ± 0.02 log, respectively. About 40% of erythromycin-resistance genes and 80% of tetracycline resistance genes could not be removed by chlorination. Chlorination was considered not effective in controlling antimicrobial resistance. More concern needs to be paid to the potential risk of antibiotic resistance genes in the wastewater after chlorination. PMID:25738838

  15. Antibiotic resistance genes & susceptibility patterns in staphylococci

    PubMed Central

    Duran, Nizami; Ozer, Burcin; Duran, Gulay Gulbol; Onlen, Yusuf; Demir, Cemil

    2012-01-01

    Background & objectives: This study was carried out to evaluate the association between the antibiotic susceptibility patterns and the antibiotic resistance genes in staphylococcal isolates obtained from various clinical samples of patients attending a teaching hospital in Hatay, Turkey. Methods: A total of 298 staphylococci clinical isolates were subjected to antimicrobial susceptibility testing. The genes implicated in resistance to oxacillin (mecA), gentamicin (aac(6’)/aph(2”), aph(3’-IIIa, ant(4’)-Ia), erythromycin (ermA, ermB, ermC, and msrA), tetracyclin (tetK, tetM), and penicillin (blaZ) were amplified using multiplex PCR method. Results: Methicillin resistance rate among 139 Staphlococcus aureus isolates was 16.5 and 25.9 per cent of S. aureus carried mecA gene. Of the 159 CoNS isolates, methicillin resistance rate was 18.9 and 29.6 per cent carried mecA gene. Ninety four isolates identified as gentamicin resistant phenotypically, contained at least one of the gentamicin resistance genes [aac(6’)/aph(2”), aph(3’)-IIIa, ant(4’)-Ia], 17 gentamicin-susceptible isolates were found as positive in terms of one or more resistance genes [aac(6’)/aph(2”), aph(3’)-IIIa, ant(4’)-Ia] by multiplex PCR. A total of 165 isolates were resistant to erythromycin, and contained at least one of the erythromycin resistance genes (ermA, ermB, ermC and msrA). Phenotypically, 106 staphylococcal isolates were resistant to tetracycline, 121 isolates carried either tetK or tetM or both resistance genes. The majority of staphylococci tested possessed the blaZ gene (89.9%). Interpretation & conclusions: The present results showed that the phenotypic antibiotic susceptibility patterns were not similar to those obtained by genotyping done by multiplex PCR. Rapid and reliable methods for antibiotic susceptibility are important to determine the appropriate therapy decisions. Multiplex PCR can be used for confirmation of the results obtained by conventional

  16. Antibiotic preparations contain DNA: a source of drug resistance genes?

    PubMed Central

    Webb, V; Davies, J

    1993-01-01

    Fluorescence measurements and polymerase chain reaction amplification of streptomycete 16S ribosomal DNA sequences were used to show that a number of antibiotic preparations employed for human and animal use are contaminated with chromosomal DNA of the antibiotic-producing organism. The DNA contains identifiable antibiotic resistance gene sequences; the uptake of this DNA by bacteria and its functional incorporation into bacterial replicons would lead to the generation of antibiotic resistance determinants. We propose that the presence of DNA encoding drug resistance in antibiotic preparations has been a factor in the rapid development of multiple antibiotic resistance in bacteria. Images PMID:8285621

  17. 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.

  18. Assessment of bacterial antibiotic resistance transfer in the gut.

    PubMed

    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

  19. The global problem of antibiotic resistance.

    PubMed

    Gootz, Thomas D

    2010-01-01

    Amid the recent attention justly focused on the potential problem of microbial sources for weapons of bioterrorism, it is also apparent that human pathogens frequently isolated from infections in patients from community and hospital sources have been growing more resistant to commonly used antibiotics. Much of the growth of multiple-drug-resistant (MDR) bacterial pathogens can be contributed to the overuse of broad-spectrum antimicrobial products. However, an equally troubling and often overlooked component of the problem involves the elegant ways in which pathogenic bacteria continually evolve complex genetic systems for acquiring and regulating an endless array of antibiotic-resistance mechanisms. Efforts to develop new antimicrobials have over the past two decades been woefully behind the rapid evolution of resistance genes developing among both gram-positive and gram-negative pathogens. Several new agents that are best suited for use in the hospital environment have been developed to combat staphylococci resistant to beta-lactam antimicrobials following acquisition of the mecA gene. However, the dramatic spread in the US of the now common community strain of Staphylococcus aureus USA300 has shifted the therapeutic need for new antibiotics useful against MRSA to the community. As the pharmaceutical industry focused on discovering new agents for use against MRSA, hospitals in many parts of the world have seen the emergence of gram-negative pathogens such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae that are clinically resistant to almost all available antimicrobials. Such MDR isolates usually contain multiple-resistance determinants, including loss of outer membrane porins via gene inactivation by chromosomally encoded insertion sequences, up-regulation of inate efflux pumps, as well as acquisition of drug-inactivating enzymes whose genes are encoded on self-transmissible plasmids, integrons, and complex transposable elements

  20. 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.

  1. 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.

  2. Will tuberculosis become resistant to all antibiotics?

    PubMed Central

    Dye, C; Espinal, M A

    2001-01-01

    The discovery of high prevalences of antibiotic resistance in some pathogens, in some parts of the world, has provoked fears of a widespread loss of drug efficacy. Here, we use a mathematical model to investigate the evolution of resistance to four major anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol and streptomycin) in 47 sites around the world. The model provides a new method of estimating the relative risk of treatment failure for patients carrying drug-resistant strains and the proportion of patients who develop resistance after failing treatment. Using estimates of these two quantities together with other published data, we reconstructed the epidemic spread of isoniazid resistance over the past 50 years. The predicted median prevalence of resistance among new cases today was 7.0% (range 0.9-64.3%), close to the 6.3% (range 0-28.1%) observed. Predicted and observed prevalences of resistance to isoniazid plus rifampicin (multidrug-resistant or MDR-TB) after 30 years of combined drug use were also similar, 0.9% (0.1-5.9%) and 1.0% (range 0-14.1%), respectively. With current data, and under prevailing treatment practices, it appears that MDR-TB will remain a localized problem, rather than becoming a global obstacle to tuberculosis control. To substantiate this result, further measurements are needed of the relative fitness of drug-resistant strains. PMID:12123297

  3. 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...

  4. Antibiotic resistances of intestinal lactobacilli isolated from wild boars.

    PubMed

    Klose, Viviana; Bayer, Katharina; Kern, Corinna; Goelß, Florian; Fibi, Silvia; Wegl, Gertrude

    2014-01-10

    Acquired antibiotic resistances have been reported in lactobacilli of various animal and food sources, but there are no data from wild boar. The objective was a preliminary examination of the antibiotic resistance prevalence of intrinsically vancomycin-resistant lactobacilli isolated from wild boar intestines and analysis of the genetic determinants implicated. Out of three wild boars, 121 lactobacilli were recovered and grouped according to their whole cell protein patterns. Initial phenotypic screening revealed that all were susceptible to erythromycin (2 μg/ml), but 30 were resistant to tetracycline (32 μg/ml). Based on Randomly Amplified Polymorphic DNA-PCR clustering, 64 strains were selected as representative genotypes for identification and minimum inhibitory concentration (MIC) determination. Partial 16S rRNA gene sequencing identified four species: (i) L. mucosae (n=57), (ii) L. reuteri (n=47), (iii) L. fermentum (n=12), and (iv) L. murinus (n=5). Most heterofermentative strains displayed low MICs for ampicillin (AMP), chloramphenicol (CHL), streptomycin (STR), kanamycin (KAN), gentamicin (GEN), erythromycin (ERY), quinupristin/dalfopristin (Q/D), and clindamycin (CLI). Atypical MICs were found mainly in L. mucosae and L. reuteri for TET, KAN, STR, AMP and CHL, but except the TET MICs of L. mucosae mostly at low level. L. murinus strains revealed atypical MICs for aminoglycosides, and/or CHL, AMP, CLI. PCR screening detected tet(W) in 12 and tet(M) in one of heterofermentative strains, as well as the aph(3')-III kanamycin gene in L. murinus. This is the first report showing acquired antibiotic resistance determinants in intestinal lactobacilli of wild boar origin.

  5. Cooperative Antibiotic Resistance in a Multi-Drug Environment

    NASA Astrophysics Data System (ADS)

    Yurtsev, Eugene; Dai, Lei; Gore, Jeff

    2013-03-01

    The emergence of antibiotic resistance in bacteria is a significant health concern. A frequent mechanism of antibiotic resistance involves the production of an enzyme which inactivates the antibiotic. By inactivating the antibiotic, resistant cells can ``share'' their resistance with other cells in the bacterial population, suggesting that it may be possible to observe cooperation between strains that inactivate different antibiotics. Here, we experimentally track the population dynamics of two E. coli strains in the presence of two different antibiotics. We find that together the strains are able to grow in antibiotic concentrations that inhibit growth of either of the strains individually. We observe that even when there is stable coexistence between the two strains, the population size of each strain can undergo large oscillations. We expect that our results will provide insight into the evolution of antibiotic resistance and the evolutionary origin of phenotypic diversity and cooperative behaviors.

  6. Membrane Proteases and Aminoglycoside Antibiotic Resistance ▿ †

    PubMed Central

    Hinz, Aaron; Lee, Samuel; Jacoby, Kyle; Manoil, Colin

    2011-01-01

    We present genetic studies that help define the functional network underlying intrinsic aminoglycoside resistance in Pseudomonas aeruginosa. Our analysis shows that proteolysis, particularly that controlled by the membrane protease FtsH, is a major determinant of resistance. First, we examined the consequences of inactivating genes controlled by AmgRS, a two-component regulator required for intrinsic tobramycin resistance. Three of the gene products account for resistance: a modulator of FtsH protease (YccA), a membrane protease (HtpX), and a membrane protein of unknown function (PA5528). Second, we screened mutations inactivating 66 predicted proteases and related functions. Insertions inactivating two FtsH protease accessory factors (HflK and HflC) and a cytoplasmic protease (HslUV) increased tobramycin sensitivity. Finally, we generated an ftsH deletion mutation. The mutation dramatically increased aminoglycoside sensitivity. Many of the functions whose inactivation increased sensitivity appeared to act independently, since multiple mutations led to additive or synergistic effects. Up to 500-fold increases in tobramycin sensitivity were observed. Most of the mutations also were highly pleiotropic, increasing sensitivity to a membrane protein hybrid, several classes of antibiotics, alkaline pH, NaCl, and other compounds. We propose that the network of proteases provides robust protection from aminoglycosides and other substances through the elimination of membrane-disruptive mistranslation products. PMID:21764915

  7. What Can Be Done about Antibiotic Resistance?

    MedlinePlus

    ... antibiotics for treating human disease. (See Antibiotics in agriculture .) Is there any international action on the antibiotic ... and reducing antibiotic use in animal farming and agriculture. Experts agree that a global system for tracking ...

  8. 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...

  9. 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

  10. 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

  11. 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.

  12. 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

  13. 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

  14. Heavy Metal Induced Antibiotic Resistance in Bacterium LSJC7.

    PubMed

    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

  15. 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.

  16. Predation and selection for antibiotic resistance in natural environments.

    PubMed

    Leisner, Jørgen J; Jørgensen, Niels O G; Middelboe, Mathias

    2016-03-01

    Genes encoding resistance to antibiotics appear, like the antibiotics themselves, to be ancient, originating long before the rise of the era of anthropogenic antibiotics. However, detailed understanding of the specific biological advantages of antibiotic resistance in natural environments is still lacking, thus limiting our efforts to prevent environmental influx of resistance genes. Here, we propose that antibiotic-resistant cells not only evade predation from antibiotic producers but also take advantage of nutrients released from cells that are killed by the antibiotic-producing bacteria. Thus, predation is potentially an important mechanism for driving antibiotic resistance during slow or stationary phase of growth when nutrients are deprived. This adds to explain the ancient nature and widespread occurrence of antibiotic resistance in natural environments unaffected by anthropogenic antibiotics. In particular, we suggest that nutrient-poor environments including indoor environments, for example, clean rooms and intensive care units may serve as a reservoir and source for antibiotic-producing as well as antibiotic-resistant bacteria.

  17. 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...

  18. U.K. Case of Throat Gonorrhea Resists Antibiotics

    MedlinePlus

    ... html U.K. Case of Throat Gonorrhea Resists Antibiotics U.S. officials concerned about potential danger of untreatable ... throat gonorrhea that proved untreatable with the standard antibiotic regimen. The patient, a heterosexual man who had ...

  19. Diversity and Antibiotic Resistance Patterns of Sphingomonadaceae Isolates from Drinking Water▿

    PubMed Central

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

    2011-01-01

    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. PMID:21705522

  20. 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.

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

    PubMed

    Khachatourians, G G

    1998-11-01

    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.

  2. Antibiotic Resistance Threats in the U.S.

    MedlinePlus

    ... and drug-resistant infections can be prevented. How Bacteria Become Resistant When bacteria are exposed to antibiotics, they start learning how to outsmart the drugs. This process occurs in bacteria found in humans, animals, and the environment. Resistant ...

  3. 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. PMID:26991378

  4. 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.

  5. [Resistance of Haemophilus sp. to antibiotics].

    PubMed

    Janicka, G; Gospodarek, E; Mikucka, A; Białek, M; Wojak, I; Krawiecka, D

    1998-02-01

    The present study was undertaken to determine the in vitro drug resistance of Haemophilus influenzae (68 isolates) and H. parainfluenzae (17 isolates). The tests susceptibility to Ampicillin, Amoxicilin/Clavulanic Acid, Cefaclor, Cefuroxime, Cotrimoxazole, Aztreonam, Ceftriaxone, Tetracycline, Ciprofloxacin, Rifampicin and Chloramphenicol were performed with a standard disk-diffusion method. The NCCLS methodology and susceptibility interpretative criteria were applied as described by the disk manufacturer. Beta-lactamase production was detected with nitrocefin impregnated disk (Cefinase, BBL Microbiology System). Resistance in nosocomially acquired Haemophilus isolates to several antibiotics was observed. Of the Haemophilus isolates 28.2% were Ampicillin in resistant, all were susceptible to the combination of Amoxicillin/Clavulanic acid. The Ampicillin-resistant strains were beta-lactamase producers. We observed the high resistance (70.1%) to Tetracycline and (28.2%) to SXT (Cotrimoxazole). All isolates of Haemophilus were susceptible to Ciprofloxacin. The low resistance percentages to Rifampin (1.2%), Aztreonam (3.5%) and Chloramphenicol (3.5%) was observed.

  6. 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

  7. Fate of antibiotic resistant cultivable heterotrophic bacteria and antibiotic resistance genes in wastewater treatment processes.

    PubMed

    Zhang, Songhe; Han, Bing; Gu, Ju; Wang, Chao; Wang, Peifang; Ma, Yanyan; Cao, Jiashun; He, Zhenli

    2015-09-01

    Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) are emerging contaminants of environmental concern. Heterotrophic bacteria in activated sludge have an important role in wastewater treatment plants (WWTPs). However, the fate of cultivable heterotrophic ARB and ARGs in WWPTs process remains unclear. In the present study, we investigated the antibiotic-resistant phenotypes of cultivable heterotrophic bacteria from influent and effluent water of three WWTPs and analysed thirteen ARGs in ARB and in activated sludge from anoxic, anaerobic and aerobic compartments. From each influent or effluent sample of the three plants, 200 isolates were randomly tested for susceptibility to 12 antibiotics. In these samples, between 5% and 64% isolates showed resistance to >9 antibiotics and the proportion of >9-drug-resistant bacteria was lower in isolates from effluent than from influent. Eighteen genera were identified in 188 isolates from influent (n=94) and effluent (n=94) of one WWTP. Six genera (Aeromonas, Bacillus, Lysinibacillus, Microbacterium, Providencia, and Staphylococcus) were detected in both influent and effluent samples. Gram-negative and -positive isolates dominated in influent and effluent, respectively. The 13 tetracycline-, sulphonamide-, streptomycin- and β-lactam-resistance genes were detected at a higher frequency in ARB from influent than from effluent, except for sulA and CTX-M, while in general, the abundances of ARGs in activated sludge from two of the three plants were higher in aerobic compartments than in anoxic ones, indicating abundant ARGs exit in the excess sledges and/or in uncultivable bacteria. These findings may be useful for elucidating the effect of WWTP on ARB and ARGs.

  8. Antibiotic Resistance in the Environment: Not the Usual Suspects.

    PubMed

    Graham, David W

    2015-07-23

    In this issue of Chemistry & Biology, Forsberg et al. (2015) show how metagenomics and biological chemistry can be combined to discover new classes of antibiotic resistance from soil metagenomes. The authors specifically reveal previously unseen resistance mechanisms and genes evident in soils, which will better inform both environmental and clinical studies on antibiotic resistance.

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

    PubMed

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

    2015-08-14

    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.

  10. Antibiotic resistance of Streptococcus agalactiae from cows with mastitis.

    PubMed

    Gao, Jian; Yu, Fu-Qing; Luo, Li-Ping; He, Jian-Zhong; Hou, Rong-Guang; Zhang, Han-Qi; Li, Shu-Mei; Su, Jing-Liang; Han, Bo

    2012-12-01

    The aim of this study was to characterise the phenotypic and genotypic antibiotic resistance patterns of Streptococcus agalactiae isolated from cows with mastitis in China. Antibiotic resistance was based on minimum inhibitory concentrations and detection of resistance genes by PCR. S. agalactiae isolates most frequently exhibited phenotypic resistance to tetracycline, while the resistance genes most frequently detected were ermB, tetL and tetM. Resistance genes were detected in some susceptible isolates, whereas no resistance genes could be detected in some resistant isolates, indicating that the resistance genotype does not accurately predict phenotypic resistance. PMID:22627045

  11. Thermosensitive antibiotic resistance plasmids in enterobacteria.

    PubMed

    Smith, H W; Parsell, Z; Green, P

    1978-11-01

    Of 775 conjugative plasmids found in enterobacteria mediating antibiotic resistance, 24 (3.1%) were thermosensitive (ts); they were most common in Klebsiella pneumoniae. Ts plasmids were also found in all the samples of sewage and river water examined. Over half of 73 ts plasmids from unrelated sources mediated resistance to chloramphenicol in addition to several other antibiotics. Many of them mediated resistance to mercury (53.4%), arsenite (38.4%) and tellurite (79.5%) but not to copper, cobalt and silver. Fifty-eight belonged to incompatibility group H2 and 12 belonged to the H1 group. Resistance to mercury, arsenite and tellurite was common in strains containing H2 plasmids but not in H1 plasmids. The 73 plasmids transferred at high rates at 22 and 28 degrees C and at lower rates at 15 degrees C; they transferred at very low rates or not at all at 37 degrees C. They could be divided into two sets according to whether they transferred at a high or at a low rate at 33 degrees C. Unlike the prototype plasmid, Rts 1, they were solely or mainly ts for transfer and not for replication and only one of them brought about a marked reduction in growth rate of its host organism at 42 degrees C. None of the 73 plasmids mediated colicin or haemolysin production. Three plasmids, all from K. pneumoniae, mediated utilization of lactose, two of sucrose and raffinose and three, all belonging to group H1, of citrate. None of the plasmids increased the pathogenicity of Salmonella typhimurium for chicks or Escherichia coli K12 for mice.

  12. [Factors of multiple resistance to antibiotics in nodule bacteria].

    PubMed

    Pariĭskaia, A N; Gorelova, O P

    1976-01-01

    Multiple resistance to antibiotics (penicillin, levomycetin, neomycin, tetracycline) was found in 15% of collection strains of nodule bacteria and in strains isolated from natural environment. PMID:1050635

  13. 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

  14. 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

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

    PubMed

    Ayhan, Dilay Hazal; Tamer, Yusuf Talha; Akbar, Mohammed; Bailey, Stacey M; Wong, Michael; Daly, Seth M; Greenberg, David E; Toprak, Erdal

    2016-09-01

    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

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

    PubMed

    Ayhan, Dilay Hazal; Tamer, Yusuf Talha; Akbar, Mohammed; Bailey, Stacey M; Wong, Michael; Daly, Seth M; Greenberg, David E; Toprak, Erdal

    2016-09-01

    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.

  17. Chromosomal mutations involved in antibiotic resistance in Staphylococcus aureus.

    PubMed

    Espedido, Bjorn A; Gosbell, Iain B

    2012-01-01

    Staphylococcus aureus is an important pathogen involved in infections in both the community and hospital setting. Strains that are resistant to multiple classes of antibiotics, particularly methicillin-resistant strains (MRSA), are prevalent in nosocomial infections and are associated with high morbidity and mortality rates. Such antibiotic-resistant strains limit the therapeutic options and place a burden on the health care system. In the hospital setting, horizontal gene transfer plays an important role in disseminating antibiotic resistant determinants among S. aureus. However, resistance to all known classes of antibiotics have been attributed to genes found within the S. aureus chromosome or to due to mutation as a result of selection pressure. Spontaneous mutations, in particular, are pivotal in the emergence of novel resistances. Consequently, newer drugs with better activity and/or antibacterial agents with novel targets need to be developed to combat and control the further spread of antibiotic resistance.

  18. Functional metagenomics for the investigation of antibiotic resistance.

    PubMed

    Mullany, Peter

    2014-04-01

    Antibiotic resistance is a major threat to human health and well-being. To effectively combat this problem we need to understand the range of different resistance genes that allow bacteria to resist antibiotics. To do this the whole microbiota needs to be investigated. As most bacteria cannot be cultivated in the laboratory, the reservoir of antibiotic resistance genes in the non-cultivatable majority remains relatively unexplored. Currently the only way to study antibiotic resistance in these organisms is to use metagenomic approaches. Furthermore, the only method that does not require any prior knowledge about the resistance genes is functional metagenomics, which involves expressing genes from metagenomic clones in surrogate hosts. In this review the methods and limitations of functional metagenomics to isolate new antibiotic resistance genes and the mobile genetic elements that mediate their spread are explored.

  19. 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

  20. 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.

  1. 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.

  2. 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. PMID:26897128

  3. 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.

  4. Analysis of antibiotic resistance in bacteria isolated from the surface microlayer and underlying water of an estuarine environment.

    PubMed

    Azevedo, Juliana S N; Araújo, Susana; Oliveira, Cláudia S; Correia, António; Henriques, Isabel

    2013-02-01

    We compared the prevalence of cultivable antibiotic-resistant bacteria and resistance genes in the surface microlayer (SML) and underlying waters (UW) of an estuary. Prevalence of resistant bacteria was determined in antibiotic-supplemented agar. Bacterial isolates from the UW (n=91) and SML (n=80), selected in media without antibiotic, were characterized concerning susceptibility against nine antibiotics. The presence of genes bla(TEM), bla(OXA-B), bla(SHV), bla(IMP), tet(A), tet(B), tet(E), tet(M), cat, sul1, sul2, sul3, aadA, IntI1, IntI2, and IntI3 was assessed by PCR. The variable regions of integrons were sequenced. Ampicillin- and streptomycin-resistant bacteria were significantly more prevalent in SML. Resistance levels among the bacterial collections were generally low, preventing detection of significant differences between SML and UW. The tet(E) gene was detected in two Aeromonas isolates and tet(M) was detected in a Pseudomonas isolate. Gene sul1 was amplified from three Aeromonas isolates. Prevalence of intI genes was 2.11%. Cassette arrays contained genes encoding resistance to aminoglycosides and chloramphenicol. A higher prevalence of antibiotic-resistant bacteria in the SML, although only detectable when bacteria were selected in antibiotic-supplemented agar, suggests that SML conditions select for antibiotic resistance. Results also showed that antibiotic resistance was uncommon among estuarine bacteria and the resistance mechanisms are probably predominantly intrinsic.

  5. 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.

  6. 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.

  7. Distribution of antibiotic resistance in urban watershed in Japan.

    PubMed

    Ham, Young-Sik; Kobori, Hiromi; Kang, Joo-Hyon; Matsuzaki, Takayuki; Iino, Michiyo; Nomura, Hayashi

    2012-03-01

    Antibiotic-resistant E. coli concentrations showed large spatial and temporal variations, with greater concentrations observed in tributaries and downstream than in the upstream and midstream. Twenty percent of the geometric mean concentrations of antibiotic-resistant E. coli in the Tama River basin (Japan) exceeded the maximum acceptable concentration of indicator E. coli established by the USEPA. The indicator E. coli concentrations were positively correlated with those of antibiotic-resistant E. coli and multiple-antibiotic-resistant E. coli (resistance to more than two kinds of antibiotics), respectively, but not the detection rate of antibiotic-resistant E. coli, implying that use of antibiotic-resistant E. coli concentration rather than the detection rate can be a better approach for water quality assessment. Multiple-antibiotic-resistant E. coli is a useful indicator for estimating the resistance diffusion, water quality degradation and public health risk potential. This assessment provides beneficial information for setting national regulatory or environmental standards and managing integrated watershed areas.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. [Old and new antibiotics for therapy of multidrug resistant bacteria].

    PubMed

    Pintado, V

    2016-09-01

    The lack of new antibiotics for multidrug-resistant bacteria is a matter of concern in microorganisms such as Pseudomonas aeruginosa, ESBL- and carbapenemase-producing Enterobacteriaceae, Acinetobacter baumannii, methicillin-resistant Staphylococcous aureus and vancomycin-resistant Enterococcus faecium. This situation has conditioned the reuse of "old" antibiotics (colistin, fosfomycin), the use of more recent antibiotics with new indications or dosage regimens (tigecycline, meropenem) and the introduction of "new" antibiotics (β-lactams, lipoglycopeptides, oxazolidinones) that are the subject of this review. PMID:27608312

  13. Antibiotic resistance gene discovery in food-producing animals.

    PubMed

    Allen, Heather K

    2014-06-01

    Numerous environmental reservoirs contribute to the widespread antibiotic resistance problem in human pathogens. One environmental reservoir of particular importance is the intestinal bacteria of food-producing animals. In this review I examine recent discoveries of antibiotic resistance genes in agricultural animals. Two types of antibiotic resistance gene discoveries will be discussed: the use of classic microbiological and molecular techniques, such as culturing and PCR, to identify known genes not previously reported in animals; and the application of high-throughput technologies, such as metagenomics, to identify novel genes and gene transfer mechanisms. These discoveries confirm that antibiotics should be limited to prudent uses.

  14. 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.

  15. 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...

  16. [Micromonospora resistence to definite antibiotics and their ability to produce structurally analogous antibiotics].

    PubMed

    Bibikova, M V; Ivanitskaia, L P; Tikhonova, A S

    1980-01-01

    Thirty six cultures of Micromonospora freshly isolated from soil samples were studied with respect to their sensitivity to a number of antibiotics of various structures and modes of action. It was found that all of them were highly sensitive to penicillin, ristomycin, tetracycline, rifampicin, streptomycin, olivomycin, carminomycin and dactinomycin. Significant differences in sensitivity of the Micromonospora cultures were revealed only with respect to gentamicin, tobramicin, erythromycin and lincomycin. Seven cultures were resistant to gentamicin and tobramicin and sensitive to all of the other antibiotics. Broad spectrum antibiotics were isolated from these cultures. The study of the antibiotic chemistry showed that they were 2-desoxystreptamine-containing aminoglycosides. Two cultures proved to be resistant to erythromycin and lincomycin. When identified with the use of antibiotic resistant staphylococcal strains, the crude antibiotic substances isolated from these cultures appeared to be not active against staphylococci resistant to erythromycin and lincomycin. By their chromatograpi- behaviour the antibiotics were close to macrolides. Therefore, it was found that production of aminoglycoside and macrolide antibiotics was most characteristic of Micromonospora. A certain correlation between resistance of Micromonospora to these 2 antibiotic groups and capacity for their production was shown. PMID:7356302

  17. Monitoring and identifying antibiotic resistance mechanisms in bacteria.

    PubMed

    Roe, M T; Pillai, S D

    2003-04-01

    Sub-therapeutic administration of antibiotics to animals is under intense scrutiny because they contribute to the dissemination of antibiotic-resistant bacteria into the food chain. Studies suggest that there is a link between the agricultural use of antibiotics and antibiotic-resistant human infections. Antibiotic-resistant organisms from animal and human wastes reenter the human and animal populations through a number of pathways including natural waters, irrigation water, drinking water, and vegetables and foods. Antibiotic usage in the United States for animal production (disease prevention and growth promotion) is estimated to be 18 million pounds annually. As much as 25 to 75% of the antibiotics administered to feedlot animals are excreted unaltered in feces. Because about 180 million dry tons of livestock and poultry waste is generated annually in the United States, it is not surprising that animal-derived antibiotic-resistant organisms are found contaminating groundwater, surface water, and food crops. It is extremely important to clearly understand the molecular mechanisms that could potentially cause lateral or horizontal gene transfer of antibiotic resistance genes among bacteria. Once the mechanisms and magnitude of resistance gene transfer are clearly understood and quantified, strategies can be instituted to reduce the potential for dissemination of these genes.

  18. "Practical knowledge" and perceptions of antibiotics and antibiotic resistance among drugsellers in Tanzanian private drugstores

    PubMed Central

    2010-01-01

    Background Studies indicate that antibiotics are sold against regulation and without prescription in private drugstores in rural Tanzania. The objective of the study was to explore and describe antibiotics sale and dispensing practices and link it to drugseller knowledge and perceptions of antibiotics and antibiotic resistance. Methods Exit customers of private drugstores in eight districts were interviewed about the drugstore encounter and drugs bought. Drugsellers filled in a questionnaire with closed- and open-ended questions about antibiotics and resistance. Data were analyzed using mixed quantitative and qualitative methods. Results Of 350 interviewed exit customers, 24% had bought antibiotics. Thirty percent had seen a health worker before coming and almost all of these had a prescription. Antibiotics were dispensed mainly for cough, stomachache, genital complaints and diarrhea but not for malaria or headache. Dispensed drugs were assessed as relevant for the symptoms or disease presented in 83% of all cases and 51% for antibiotics specifically. Non-prescribed drugs were assessed as more relevant than the prescribed. The knowledge level of the drugseller was ranked as high or very high by 75% of the respondents. Seventy-five drugsellers from three districts participated. Seventy-nine percent stated that diseases caused by bacteria can be treated with antibiotics but 24% of these also said that antibiotics can be used for treating viral disease. Most (85%) said that STI can be treated with antibiotics while 1% said the same about headache, 4% general weakness and 3% 'all diseases'. Seventy-two percent had heard of antibiotic resistance. When describing what an antibiotic is, the respondents used six different kinds of keywords. Descriptions of what antibiotic resistance is and how it occurs were quite rational from a biomedical point of view with some exceptions. They gave rise to five categories and one theme: Perceiving antibiotic resistance based on

  19. [The threat of antibiotic resistance to nursing homes].

    PubMed

    Bonten, M J M

    2016-01-01

    Antibiotic resistance is considered a major threat to healthcare. The Dutch government recently announced additional measures to contain this threat, one of these being the creation of regional care networks dedicated to control antibiotic resistance. Among the anticipated activities of these networks is quantifying the prevalence of antibiotic resistance in nursing homes, through regular point-prevalence surveillance studies. There is a broadly felt belief that nursing homes might be a 'mer à boire' of antibiotic resistance. Although scientific data do not support that claim, it is nevertheless likely that the planned investigations will identify yet unknown clusters of ESBL-carriers, necessitating infection control measures. Given the absence of an acute problem and the consequences for nursing home management, staff and clients of point-prevalence surveillance studies, a staged approach for investigating antibiotic resistance in nursing homes should be considered. PMID:27650029

  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

    2016-01-01

    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. PMID:27572838

  1. [The threat of antibiotic resistance to nursing homes].

    PubMed

    Bonten, M J M

    2016-01-01

    Antibiotic resistance is considered a major threat to healthcare. The Dutch government recently announced additional measures to contain this threat, one of these being the creation of regional care networks dedicated to control antibiotic resistance. Among the anticipated activities of these networks is quantifying the prevalence of antibiotic resistance in nursing homes, through regular point-prevalence surveillance studies. There is a broadly felt belief that nursing homes might be a 'mer à boire' of antibiotic resistance. Although scientific data do not support that claim, it is nevertheless likely that the planned investigations will identify yet unknown clusters of ESBL-carriers, necessitating infection control measures. Given the absence of an acute problem and the consequences for nursing home management, staff and clients of point-prevalence surveillance studies, a staged approach for investigating antibiotic resistance in nursing homes should be considered.

  2. 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. PMID:26852201

  3. Metagenomic Insights into Transferable Antibiotic Resistance in Oral Bacteria.

    PubMed

    Sukumar, S; Roberts, A P; Martin, F E; Adler, C J

    2016-08-01

    Antibiotic resistance is considered one of the greatest threats to global public health. Resistance is often conferred by the presence of antibiotic resistance genes (ARGs), which are readily found in the oral microbiome. In-depth genetic analyses of the oral microbiome through metagenomic techniques reveal a broad distribution of ARGs (including novel ARGs) in individuals not recently exposed to antibiotics, including humans in isolated indigenous populations. This has resulted in a paradigm shift from focusing on the carriage of antibiotic resistance in pathogenic bacteria to a broader concept of an oral resistome, which includes all resistance genes in the microbiome. Metagenomics is beginning to demonstrate the role of the oral resistome and horizontal gene transfer within and between commensals in the absence of selective pressure, such as an antibiotic. At the chairside, metagenomic data reinforce our need to adhere to current antibiotic guidelines to minimize the spread of resistance, as such data reveal the extent of ARGs without exposure to antimicrobials and the ecologic changes created in the oral microbiome by even a single dose of antibiotics. The aim of this review is to discuss the role of metagenomics in the investigation of the oral resistome, including the transmission of antibiotic resistance in the oral microbiome. Future perspectives, including clinical implications of the findings from metagenomic investigations of oral ARGs, are also considered.

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

    PubMed

    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.

  5. 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

  6. Isolated cell behavior drives the evolution of antibiotic resistance

    PubMed Central

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

    2015-01-01

    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. PMID:26227664

  7. Crystal Structure of the Carbapenem Intrinsic Resistance Protein CarG

    PubMed Central

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

    2015-01-01

    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. PMID:24583229

  8. 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.

  9. Effect of Surfactants on Antibiotic Resistance

    PubMed Central

    Suling, William J.; O'Leary, William M.

    1975-01-01

    The effectiveness of surfactants as potentiators of antibiotic activity on several resistant strains of bacteria, selected from clinical sources and laboratory collections, was studied using a tube dilution assay. Bacterial strains included members of the Enterobacteriaceae and staphylococci. Cetyltrimethylammonium bromide (CTAB), Tween 80 (Tw80), a mixture of n-alkyldimethyl betaines (L14), and alpha-(2,4,5-trichlorophenoxy) propionic acid (TCP) were tested in combination with pencillin G (PenG), methicillin (Met), streptomycin (Sm), polymyxin B (PmB), and chlortetracycline (CTC). Growth response to the drug combinations was compared with the response to each drug alone. CTAB and L14 but not Tw80 or TCP were found to potentiate the activity of CTC on strains of Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. Studies on the inhibition of protein synthesis by CTC in cells of a strain of E. coli suggested that the surfactants increased the uptake of antibiotic into the cells. CTAB and L14 almost completely sensitized strains of P. mirabilis, Serratia marcescens, K. pneumoniae, and E. coli to PmB. With the exception of K. pneumoniae, TCP was also effective in potentiating the activity of PmB on the above strains whereas Tw80 showed potentiation only with a strain of E. coli. CTAB and L14 but not TCP or Tw80 potentiated the activity of PenG but not Met on strains of staphylococci. Studies of penicillinase in the cells suggested that the surfactants inhibited the formation of this enzyme possibly at the level of induction. None of the surfactants were found to potentiate the activity of Sm. PMID:1101823

  10. 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

  11. 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

  12. 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. PMID:27126035

  13. 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

  14. Genomic Insights into Intrinsic and Acquired Drug Resistance Mechanisms in Achromobacter xylosoxidans

    PubMed Central

    Hu, Yongfei; Zhu, Yuying; Ma, Yanan; Liu, Fei; Lu, Na; Yang, Xi; Luan, Chunguang; Yi, Yong

    2014-01-01

    Achromobacter xylosoxidans is an opportunistic pathogen known to be resistant to a wide range of antibiotics; however, the knowledge about the drug resistance mechanisms is limited. We used a high-throughput sequencing approach to sequence the genomes of the A. xylosoxidans type strain ATCC 27061 and a clinical isolate, A. xylosoxidans X02736, and then we used different bioinformatics tools to analyze the drug resistance genes in these bacteria. We obtained the complete genome sequence for A. xylosoxidans ATCC 27061 and the draft sequence for X02736. We predicted a total of 50 drug resistance-associated genes in the type strain, including 5 genes for β-lactamases and 17 genes for efflux pump systems; these genes are also conserved among other A. xylosoxidans genomes. In the clinical isolate, except for the conserved resistance genes, we also identified several acquired resistance genes carried by a new transposon embedded in a novel integrative and conjugative element. Our study provides new insights into the intrinsic and acquired drug resistance mechanisms in A. xylosoxidans, which will be helpful for better understanding the physiology of A. xylosoxidans and the evolution of antibiotic resistance in this bacterium. PMID:25487802

  15. 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.

  16. 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.

  17. Effects of sarA inactivation on the intrinsic multidrug resistance mechanism of Staphylococcus aureus.

    PubMed

    O'Leary, Jessica O; Langevin, Mark J; Price, Christopher T D; Blevins, Jon S; Smeltzer, Mark S; Gustafson, John E

    2004-08-15

    The sarA locus of Staphylococccus aureus regulates the synthesis of over 100 genes on the S. aureus chromosome. We now report the effects of sarA inactivation on intrinsic multidrug resistance expression by S. aureus. In a strain-dependent fashion, sarA::kan mutants of three unrelated strains of S. aureus demonstrated significantly increased susceptibility to five or more of the following substances: the antibiotics ciprofloxacin, fusidic acid, and vancomycin; the DNA-intercalating agent ethidium; and four common household cleaner formulations. In addition, all three sarA::kan mutants demonstrated significantly increased accumulation of ciprofloxacin and one sarA::kan mutant demonstrated increased ethidium accumulation. Our data therefore indicate that sarA plays a role in the intrinsic multidrug resistance mechanism expressed by S. aureus, in part by regulating drug accumulation.

  18. Antibiotic resistance to Propionobacterium acnes: worldwide scenario, diagnosis and management.

    PubMed

    Sardana, Kabir; Gupta, Tanvi; Garg, Vijay K; Ghunawat, Sneha

    2015-07-01

    Antibiotic resistance in cutaneous Propionobacterium is a global problem. As a general rule, resistance levels are high to macrolides, trimethoprim/sulfamethoxazole and clindamycin, while tetracyclines and levofloxacin have low resistance potential. Newer preparations like doxycycline MR and doxycycline 20 mg are subantimicrobial and may not lead to resistance. Sampling techniques are crucial to determine resistance. Genomic evaluation using 16S ribosomal RNA gene sequencing can be useful in diagnosing mutations and mapping phylotypes of Propionobacterium acnes. Resistance may lead to slow response and relapses. Apart from benzoyl peroxide, azelaic acid, topical dapsone, oral zinc and retinoids, novel molecules with little resistance potential include octadecenedioic acid, phytosphingosine, lauric acid, retapamulin, resveratrol, T-3912 and NB-003. The use of oral retinoids and non-antibiotics like zinc can prevent resistance and help reduce the dependence on antibiotics.

  19. Antibiotic resistance to Propionobacterium acnes: worldwide scenario, diagnosis and management.

    PubMed

    Sardana, Kabir; Gupta, Tanvi; Garg, Vijay K; Ghunawat, Sneha

    2015-07-01

    Antibiotic resistance in cutaneous Propionobacterium is a global problem. As a general rule, resistance levels are high to macrolides, trimethoprim/sulfamethoxazole and clindamycin, while tetracyclines and levofloxacin have low resistance potential. Newer preparations like doxycycline MR and doxycycline 20 mg are subantimicrobial and may not lead to resistance. Sampling techniques are crucial to determine resistance. Genomic evaluation using 16S ribosomal RNA gene sequencing can be useful in diagnosing mutations and mapping phylotypes of Propionobacterium acnes. Resistance may lead to slow response and relapses. Apart from benzoyl peroxide, azelaic acid, topical dapsone, oral zinc and retinoids, novel molecules with little resistance potential include octadecenedioic acid, phytosphingosine, lauric acid, retapamulin, resveratrol, T-3912 and NB-003. The use of oral retinoids and non-antibiotics like zinc can prevent resistance and help reduce the dependence on antibiotics. PMID:26025191

  20. 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.

  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. Resistance to antibiotics: are we in the post-antibiotic era?

    PubMed

    Alanis, Alfonso J

    2005-01-01

    Serious infections caused by bacteria that have become resistant to commonly used antibiotics have become a major global healthcare problem in the 21st century. They not only are more severe and require longer and more complex treatments, but they are also significantly more expensive to diagnose and to treat. Antibiotic resistance, initially a problem of the hospital setting associated with an increased number of hospital-acquired infections usually in critically ill and immunosuppressed patients, has now extended into the community causing severe infections difficult to diagnose and treat. The molecular mechanisms by which bacteria have become resistant to antibiotics are diverse and complex. Bacteria have developed resistance to all different classes of antibiotics discovered to date. The most frequent type of resistance is acquired and transmitted horizontally via the conjugation of a plasmid. In recent times new mechanisms of resistance have resulted in the simultaneous development of resistance to several antibiotic classes creating very dangerous multidrug-resistant (MDR) bacterial strains, some also known as "superbugs". The indiscriminate and inappropriate use of antibiotics in outpatient clinics, hospitalized patients and in the food industry is the single largest factor leading to antibiotic resistance. In recent years, the number of new antibiotics licensed for human use in different parts of the world has been lower than in the recent past. In addition, there has been less innovation in the field of antimicrobial discovery research and development. The pharmaceutical industry, large academic institutions or the government are not investing the necessary resources to produce the next generation of newer safe and effective antimicrobial drugs. In many cases, large pharmaceutical companies have terminated their anti-infective research programs altogether due to economic reasons. The potential negative consequences of all these events are relevant because

  3. 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

  4. 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

  5. Fate of Antibiotics and Antibiotic Resistance during Digestion and Composting: A Review.

    PubMed

    Youngquist, Caitlin P; Mitchell, Shannon M; Cogger, Craig G

    2016-03-01

    Antibiotics and antibiotic-resistant bacteria (ARB) enter the environment through municipal and agricultural waste streams and pose a potential risk to human and livestock health through either direct exposure to antibiotic-resistant pathogens or selective pressure on the soil microbial community. This review summarizes current literature on the fate of antibiotics, ARB, and antibiotic resistance genes (ARGs) during anaerobic digestion and composting of manure and wastewater residuals. Studies have shown that removal of antibiotics varies widely during mesophilic anaerobic digestion, even within the same class of antibiotics. Research on ARB shows a wide range of removal under mesophilic conditions, with nearly complete removal under thermophilic conditions. Research on 16 antibiotics in 11 different studies using both bench-scale and farm-scale composting systems demonstrates that composting significantly reduces levels of extractable antibiotics in livestock manure in nearly all cases. Calculated half-lives ranged from 0.9 to 16 d for most antibiotics. There is more limited evidence that levels of ARB are also reduced by composting. Studies of the fate of ARGs show mixed evidence for removal during both mesophilic and thermophilic anaerobic digestion and during thermophilic composting. Antibiotic resistance genes are DNA structures, so they may persist until the DNA structure is degraded, yet the bacterium may have been rendered nonviable long before the DNA is completely degraded. Additional research would be of value to determine optimum anaerobic digestion and composting conditions for removal of ARB and to increase understanding of the fate of ARGs during anaerobic digestion and composting. PMID:27065401

  6. Current status of antibiotic resistance in animal production.

    PubMed

    Franklin, A

    1999-01-01

    It is generally accepted that the more antibiotics we use, the faster bacteria will develop resistance. Further it has been more or less accepted that once an antibiotic is withdrawn from the clinic, the resistance genes will eventually disappear, [table: see text] since they will no more be of any survival value for the bacterial cell. However, recent research has shown that after a long time period of exposure to antibiotics, certain bacterial species may adapt to this environment in such a way that they keep their resistance genes stably also after the removal of antibiotics. Thus, there is reason to believe that once resistance has developed it will not even in the long term be eradicated. What then can we do not to increase further the already high level of antibiotic-resistant bacteria in animals? We should of course encourage a prudent use of these valuable drugs. In Sweden antibiotics are not used for growth promoting purposes and are available only after veterinary prescription on strict indications. Generally, antimicrobial treatment of animals on individual or on herd basis should not be considered unless in connection with relevant diagnostics. The amounts of antibiotics used and the development of resistance in important pathogens should be closely monitored. Furthermore, resistance monitoring in certain non-pathogenic intestinal bacteria, which may serve as a reservoir for resistance genes is probably more important than hitherto anticipated. Once the usage of or resistance to a certain antibiotic seems to increase in an alarming way, steps should be taken to limit the usage of the drug in order to prevent further spread of resistance genes in animals, humans and the environment. Better methods for detecting and quantifying antibiotic resistance have to be developed. Screening methods must be standardized and evaluated in order to obtain comparable and reliable results from different countries. The genetic mechanisms for development of resistance and

  7. 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...

  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. 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...

  10. 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.

  11. 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)

  12. 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.

  13. 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.

  14. 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

  15. Antibiotic-resistant soil bacteria in transgenic plant fields

    PubMed Central

    Demanèche, Sandrine; Sanguin, Hervé; Poté, John; Navarro, Elisabeth; Bernillon, Dominique; Mavingui, Patrick; Wildi, Walter; Vogel, Timothy M.; Simonet, Pascal

    2008-01-01

    Understanding the prevalence and polymorphism of antibiotic resistance genes in soil bacteria and their potential to be transferred horizontally is required to evaluate the likelihood and ecological (and possibly clinical) consequences of the transfer of these genes from transgenic plants to soil bacteria. In this study, we combined culture-dependent and -independent approaches to study the prevalence and diversity of bla genes in soil bacteria and the potential impact that a 10-successive-year culture of the transgenic Bt176 corn, which has a blaTEM marker gene, could have had on the soil bacterial community. The bla gene encoding resistance to ampicillin belongs to the beta-lactam antibiotic family, which is widely used in medicine but is readily compromised by bacterial antibiotic resistance. Our results indicate that soil bacteria are naturally resistant to a broad spectrum of beta-lactam antibiotics, including the third cephalosporin generation, which has a slightly stronger discriminating effect on soil isolates than other cephalosporins. These high resistance levels for a wide range of antibiotics are partly due to the polymorphism of bla genes, which occur frequently among soil bacteria. The blaTEM116 gene of the transgenic corn Bt176 investigated here is among those frequently found, thus reducing any risk of introducing a new bacterial resistance trait from the transgenic material. In addition, no significant differences were observed in bacterial antibiotic-resistance levels between transgenic and nontransgenic corn fields, although the bacterial populations were different. PMID:18292221

  16. [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.

  17. 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...

  18. 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.

  19. 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. PMID:25633938

  20. 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.

  1. 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

  2. Antibiotic Methylation: A New Mechanism of Antimicrobial Resistance.

    PubMed

    Malone, Kerri M; Gordon, Stephen V

    2016-10-01

    In new research on Mycobacterium tuberculosis, the causative agent of tuberculosis, Warrier and colleagues have discovered a novel mode of bacterial drug resistance, namely antibiotic inactivation via N-methylation.

  3. Antibiotic Resistance in India: Drivers and Opportunities for Action.

    PubMed

    Laxminarayan, Ramanan; Chaudhury, Ranjit Roy

    2016-03-01

    Ramanan Laxminarayan and Ranjit Roy Chaudhury examine the factors encouraging the emergence of antibiotic resistance in India, the implications nationally and internationally, and what might be done to help. PMID:26934098

  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. Antibiotic Resistance in India: Drivers and Opportunities for Action.

    PubMed

    Laxminarayan, Ramanan; Chaudhury, Ranjit Roy

    2016-03-01

    Ramanan Laxminarayan and Ranjit Roy Chaudhury examine the factors encouraging the emergence of antibiotic resistance in India, the implications nationally and internationally, and what might be done to help.

  6. Antibiotic Methylation: A New Mechanism of Antimicrobial Resistance.

    PubMed

    Malone, Kerri M; Gordon, Stephen V

    2016-10-01

    In new research on Mycobacterium tuberculosis, the causative agent of tuberculosis, Warrier and colleagues have discovered a novel mode of bacterial drug resistance, namely antibiotic inactivation via N-methylation. PMID:27593675

  7. 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. PMID:27397433

  8. 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

  9. 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

  10. 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...

  11. 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

  12. Inactivation of antibiotics and the dissemination of resistance genes.

    PubMed

    Davies, J

    1994-04-15

    The emergence of multidrug-resistant bacteria is a phenomenon of concern to the clinician and the pharmaceutical industry, as it is the major cause of failure in the treatment of infectious diseases. The most common mechanism of resistance in pathogenic bacteria to antibiotics of the aminoglycoside, beta-lactam (penicillins and cephalosporins), and chloramphenicol types involves the enzymic inactivation of the antibiotic by hydrolysis or by formation of inactive derivatives. Such resistance determinants most probably were acquired by pathogenic bacteria from a pool of resistance genes in other microbial genera, including antibiotic-producing organisms. The resistance gene sequences were subsequently integrated by site-specific recombination into several classes of naturally occurring gene expression cassettes (typically "integrons") and disseminated within the microbial population by a variety of gene transfer mechanisms. Although bacterial conjugation once was believed to be restricted in host range, it now appears that this mechanism of transfer permits genetic exchange between many different bacterial genera in nature.

  13. The ABC of Ribosome-Related Antibiotic Resistance.

    PubMed

    Wilson, Daniel N

    2016-01-01

    The increase in multidrug-resistant pathogenic bacteria is limiting the utility of our current arsenal of antimicrobial agents. Mechanistically understanding how bacteria obtain antibiotic resistance is a critical first step to the development of improved inhibitors. One common mechanism for bacteria to obtain antibiotic resistance is by employing ATP-binding cassette (ABC) transporters to actively pump the drug from the cell. The ABC-F family includes proteins conferring resistance to a variety of clinically important ribosome-targeting antibiotics; however, controversy remains as to whether resistance is conferred via efflux like other ABC transporters or whether another mechanism, such as ribosome protection, is at play. A recent study by Sharkey and coworkers (L. K. Sharkey, T. A. Edwards, and A. J. O'Neill, mBio 7:e01975-15, 2016, http://dx.doi.org/10.1128/mBio.01975-15) provides strong evidence that ABC-F proteins conferring antibiotic resistance utilize ribosome protection mechanisms, namely, by interacting with the ribosome and displacing the drug from its binding site, thus revealing a novel role for ABC-F proteins in antibiotic resistance. PMID:27143393

  14. The ABC of Ribosome-Related Antibiotic Resistance.

    PubMed

    Wilson, Daniel N

    2016-05-03

    The increase in multidrug-resistant pathogenic bacteria is limiting the utility of our current arsenal of antimicrobial agents. Mechanistically understanding how bacteria obtain antibiotic resistance is a critical first step to the development of improved inhibitors. One common mechanism for bacteria to obtain antibiotic resistance is by employing ATP-binding cassette (ABC) transporters to actively pump the drug from the cell. The ABC-F family includes proteins conferring resistance to a variety of clinically important ribosome-targeting antibiotics; however, controversy remains as to whether resistance is conferred via efflux like other ABC transporters or whether another mechanism, such as ribosome protection, is at play. A recent study by Sharkey and coworkers (L. K. Sharkey, T. A. Edwards, and A. J. O'Neill, mBio 7:e01975-15, 2016, http://dx.doi.org/10.1128/mBio.01975-15) provides strong evidence that ABC-F proteins conferring antibiotic resistance utilize ribosome protection mechanisms, namely, by interacting with the ribosome and displacing the drug from its binding site, thus revealing a novel role for ABC-F proteins in antibiotic resistance.

  15. 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. PMID:26928861

  16. 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.

  17. 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

  18. The isolation of antibiotic resistant coliforms from meat and sewage.

    PubMed

    Bensink, J C; Frost, A J; Mathers, W; Mutimer, M D; Rankin, G; Woolcock, J B

    1981-01-01

    Beef and pig carcases, meat products, frozen chickens, and sewage were examined in 3 separate surveys for antibiotic resistant coliforms. Escherichia coli was isolated from 18 of 50 beef carcases; the numbers were low and resistance was found only to tetracycline. E. coli was isolated from 45 to 50 pig carcases; the numbers were high and showed a range of patterns of multiple antibiotic resistance. In meat products, the proportion of E. coli in contaminating organisms was low, and most resistance found was to tetracycline and streptomycin. E. coli was isolated from 66 of 75 chickens and these gave 23 patterns of antibiotic resistance, often multiple. Sewage from hospital or domestic origin and abattoir effluent yielded approximately 10(6) coliforms/ml, most of which were resistant to one or more antibiotics; few of those from hospital or domestic origin however, were classified as E. coli of faecal origin. Twenty-four patterns of resistance were found in coliforms from domestic sewage, 19 from hospital sewage and 11 from abattoir effluent. Transfer of resistance, often multiple, was achieved from 55% of 447 resistant strains to an E. coli K12 recipient. Much more information is required on the prevalence of R-factors in bacteria associated with food producing animals and their products. PMID:7016108

  19. Selective Conditions for a Multidrug Resistance Plasmid Depend on the Sociality of Antibiotic Resistance.

    PubMed

    Bottery, Michael J; Wood, A Jamie; Brockhurst, Michael A

    2016-04-01

    Multidrug resistance (MDR) plasmids frequently carry antibiotic resistance genes conferring qualitatively different mechanisms of resistance. We show here that the antibiotic concentrations selecting for the RK2 plasmid inEscherichia colidepend upon the sociality of the drug resistance: the selection for selfish drug resistance (efflux pump) occurred at very low drug concentrations, just 1.3% of the MIC of the plasmid-free antibiotic-sensitive strain, whereas selection for cooperative drug resistance (modifying enzyme) occurred at drug concentrations exceeding the MIC of the plasmid-free strain. PMID:26787694

  20. Selective Conditions for a Multidrug Resistance Plasmid Depend on the Sociality of Antibiotic Resistance

    PubMed Central

    Wood, A. Jamie; Brockhurst, Michael A.

    2016-01-01

    Multidrug resistance (MDR) plasmids frequently carry antibiotic resistance genes conferring qualitatively different mechanisms of resistance. We show here that the antibiotic concentrations selecting for the RK2 plasmid in Escherichia coli depend upon the sociality of the drug resistance: the selection for selfish drug resistance (efflux pump) occurred at very low drug concentrations, just 1.3% of the MIC of the plasmid-free antibiotic-sensitive strain, whereas selection for cooperative drug resistance (modifying enzyme) occurred at drug concentrations exceeding the MIC of the plasmid-free strain. PMID:26787694

  1. 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

  2. Antibiotic and antimicrobial peptide combinations: synergistic inhibition of Pseudomonas fluorescens and antibiotic-resistant variants.

    PubMed

    Naghmouchi, Karim; Le Lay, Christophe; Baah, John; Drider, Djamel

    2012-02-01

    Variants resistant to penicillin G (RvP), streptomycin (RvS), lincomycin (RvL) and rifampicin (RvR) were developed from a colistin-sensitive isolate of Pseudomonas fluorescens LRC-R73 (P. fluorescens). Cell fatty acid composition, K(+) efflux and sensitivity to antimicrobial peptides (nisin Z, pediocin PA-1/AcH and colistin) alone or combined with antibiotics were determined. P. fluorescens was highly sensitive to kanamycin, tetracycline and chloramphenicol at minimal inhibitory concentrations of 0.366, 0.305 and 0.732 μg/ml respectively. P. fluorescens, RvP, RvS, RvL and RvR were resistant to nisin Z and pediocin PA-1/AcH at concentrations ≥100 μg/ml but sensitive to colistin at 0.076, 0.043, 0.344, 0.344 and 0.258 μg/ml respectively. A synergistic inhibitory effect (FICI ≤0.5) was observed when resistant variants were treated with peptide/antibiotic combinations. No significant effect on K(+) efflux from the resistant variants in the presence of antibiotics or peptides alone or combined was observed. The proportion of C16:0 was significantly higher in antibiotic-resistant variants than in the parent strain, accounting for 32.3%, 46.49%, 43.3%, 40.1% and 44.1% of the total fatty acids in P. fluorescens, RvP, RvS, RvL and RvR respectively. Combination of antibiotics with antimicrobial peptides could allow reduced use of antibiotics in medical applications and could help slow the emergence of bacteria resistant to antibiotics. PMID:22172555

  3. Ultraviolet disinfection of antibiotic resistant bacteria and their antibiotic resistance genes in water and wastewater.

    PubMed

    McKinney, Chad W; Pruden, Amy

    2012-12-18

    Disinfection of wastewater treatment plant effluent may be an important barrier for limiting the spread of antibiotic-resistant bacteria (ARBs) and antibiotic resistance genes (ARGs). While ideally disinfection should destroy ARGs, to prevent horizontal gene transfer to downstream bacteria, little is known about the effect of conventional water disinfection technologies on ARGs. This study examined the potential of UV disinfection to damage four ARGs, mec(A), van(A), tet(A), and amp(C), both in extracellular form and present within a host ARBs: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), Escherichia coli SMS-3-5, and Pseudomonas aeruginosa 01, respectively. An extended amplicon-length quantitative polymerase chain reaction assay was developed to enhance capture of ARG damage events and also to normalize to an equivalent length of target DNA (∼1000 bp) for comparison. It was found that the two Gram-positive ARBs (MRSA and VRE) were more resistant to UV disinfection than the two Gram-negative ARBs (E. coli and P. aeruginosa). The two Gram-positive organisms also possessed smaller total genome sizes, which could also have reduced their susceptibility to UV because of fewer potential pyrimidine dimer targets. An effect of cell type on damage to ARGs was only observed in VRE and P. aeruginosa, the latter potentially because of extracellular polymeric substances. In general, damage of ARGs required much greater UV doses (200-400 mJ/cm² for 3- to 4-log reduction) than ARB inactivation (10-20 mJ/cm² for 4- to 5-log reduction). The proportion of amplifiable ARGs following UV treatment exhibited a strong negative correlation with the number of adjacent thymines (Pearson r < -0.9; p < 0.0001). ARBs surviving UV treatment were negatively correlated with total genome size (Pearson r < -0.9; p < 0.0001) and adjacent cytosines (Pearson r < -0.88; p < 0.0001) but positively correlated with adjacent thymines (Pearson r

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

    PubMed

    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

  5. 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

  6. [New aspects of antibiotic resistance and possibilities of its prevention].

    PubMed

    Blahová, J; Králiková, K; Krcméry, V

    2001-08-01

    New phenomena of the antibiotic resistance in bacteria have recently appeared. The may hold present explosive development of resistance and prevent its transferability from multiple drug resistant bacteria to still sensitive ones. They may prevent the production of so-called extended-spectrum beta-lactamases (ESBLs) among Enterobacteriaceae producing resistance virtually to all penicillins and cephalosporins with exception of those antibiotics potentiated by clavulanic acid or sulbactam, the resistance to vancomycin in enterococci and staphylococce, and the resistance of Stenotrophomonas maltophilia. Factors participating on the development of resistance include: a) transferability of resistance genes among bacteria which explosively change susceptible strains to resistant ones, b) dosage and types of antibiotics which cause the selection pressure to certain species of bacteria, c) level of organization and strict adherence to hygienic and anti-epidemic regimen starting with the entry of patients into the hospital. Analyses are necessary to check whether the patient brings resistant bacteria with a transferable resistance (with ESBLs) into the hospital. Preventive measures would be strictly applied to stop the clonal spread of resistant strains among the patients and/or hospital environment, which occurs if these strains have such opportunity. Last, but not least to be considered is the dosage, composition and rationality of administration of antibacterials, mainly in post-operative prophylaxis in intensive care units, in so-called empirical usage, etc. At the same time, it would be highly unethical to hesitate with application of antibacterials to patients when it is justified, necessary and rational. Hospital antibiotics policy should rationally decide between these alternatives in each application of antibiotics or their combinations.

  7. 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. PMID:26445858

  8. 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

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

    PubMed

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

    2016-01-01

    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. PMID:27383577

  10. 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.

  11. Parallel evolutionary pathways to antibiotic resistance selected by biocide exposure

    PubMed Central

    Webber, Mark A.; Whitehead, Rebekah N.; Mount, Manuella; Loman, Nick J.; Pallen, Mark J.; Piddock, Laura J. V.

    2015-01-01

    Objectives Biocides are widely used to prevent infection. We aimed to determine whether exposure of Salmonella to various biocides could act as a driver of antibiotic resistance. Methods Salmonella enterica serovar Typhimurium was exposed to four biocides with differing modes of action. Antibiotic-resistant mutants were selected during exposure to all biocides and characterized phenotypically and genotypically to identify mechanisms of resistance. Results All biocides tested selected MDR mutants with decreased antibiotic susceptibility; these occurred randomly throughout the experiments. Mutations that resulted in de-repression of the multidrug efflux pump AcrAB-TolC were seen in MDR mutants. A novel mutation in rpoA was also selected and contributed to the MDR phenotype. Other mutants were highly resistant to both quinolone antibiotics and the biocide triclosan. Conclusions This study shows that exposure of bacteria to biocides can select for antibiotic-resistant mutants and this is mediated by clinically relevant mechanisms of resistance prevalent in human pathogens. PMID:25953808

  12. Prediction of antibiotic resistance by gene expression profiles

    PubMed Central

    Suzuki, Shingo; Horinouchi, Takaaki; Furusawa, Chikara

    2014-01-01

    Although many mutations contributing to antibiotic resistance have been identified, the relationship between the mutations and the related phenotypic changes responsible for the resistance has yet to be fully elucidated. To better characterize phenotype–genotype mapping for drug resistance, here we analyse phenotypic and genotypic changes of antibiotic-resistant Escherichia coli strains obtained by laboratory evolution. We demonstrate that the resistances can be quantitatively predicted by the expression changes of a small number of genes. Several candidate mutations contributing to the resistances are identified, while phenotype–genotype mapping is suggested to be complex and includes various mutations that cause similar phenotypic changes. The integration of transcriptome and genome data enables us to extract essential phenotypic changes for drug resistances. PMID:25517437

  13. 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...

  14. Antibiotic Resistant Microbiota in the Swine Intestinal Tract

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The healthy swine intestine is populated by upwards of 500 bacterial species, mainly obligate anaerobes. Our research focuses on the roles of these commensal bacteria in antimicrobial resistance and on interventions to reduce the prevalence of antibiotic resistant bacteria. In comparisons of intes...

  15. Role of porins in intrinsic antibiotic resistance of Pseudomonas cepacia.

    PubMed Central

    Parr, T R; Moore, R A; Moore, L V; Hancock, R E

    1987-01-01

    The measured outer membrane permeability of Pseudomonas cepacia to the beta-lactam nitrocefin was low: approximately 10 times less than that of Escherichia coli and comparable to that of Pseudomonas aeruginosa. The purified P. cepacia porin demonstrated an average single channel conductance in 1 M KCl of 0.23 nS. Images PMID:3032087

  16. Chlorinated phenol-induced physiological antibiotic resistance in Pseudomonas aeruginosa.

    PubMed

    Muller, Jocelyn Fraga; Ghosh, Sudeshna; Ikuma, Kaoru; Stevens, Ann M; Love, Nancy G

    2015-11-01

    Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an opportunistic pathogen with the ability to rapidly develop multidrug resistance under selective pressure. Previous work demonstrated that upon exposure to the environmental contaminant pentachlorophenol (PCP), P. aeruginosa PAO1 increases expression of multiple multidrug efflux pumps, including the MexAB-OprM pump. The current study describes increases in the antibiotic resistance of PAO1 upon exposure to PCP and other chlorinated organics, including triclosan. Only exposure to chlorinated phenols induced the mexAB-oprM-mediated antibiotic-resistant phenotype. Thus, chlorinated phenols have the potential to contribute to transient phenotypic increases of antibiotic resistance that are relevant when both compounds are present in the environment.

  17. [Antimicrobial resistance forever? Judicious and appropriate use of antibiotics].

    PubMed

    Cagliano, Stefano

    2015-06-01

    This article takes its cue from the original work of sir Alexander Fleming on penicillin, published in the first issue of Recenti Progressi in Medicina in 1946 and reproduced here on the occasion of the approaching 70-year anniversary of the journal. In 1928, at the time when penicillin was discovered, it could not be imagined that bacterial resistance to antibiotics would develop so rapidly: the introduction of every new class of antibiotics has been shortly followed by the emergence of new strains of bacteria resistant to that class. Bacterial resistance to antibiotic treatment is a huge concern. In this respect, an action plan against antimicrobial resistance has been devised in the United States that is targeted for a 50% reduction over the next five years.

  18. [Antimicrobial resistance forever? Judicious and appropriate use of antibiotics].

    PubMed

    Cagliano, Stefano

    2015-06-01

    This article takes its cue from the original work of sir Alexander Fleming on penicillin, published in the first issue of Recenti Progressi in Medicina in 1946 and reproduced here on the occasion of the approaching 70-year anniversary of the journal. In 1928, at the time when penicillin was discovered, it could not be imagined that bacterial resistance to antibiotics would develop so rapidly: the introduction of every new class of antibiotics has been shortly followed by the emergence of new strains of bacteria resistant to that class. Bacterial resistance to antibiotic treatment is a huge concern. In this respect, an action plan against antimicrobial resistance has been devised in the United States that is targeted for a 50% reduction over the next five years. PMID:26076416

  19. Pediatric fecal microbiota harbor diverse and novel antibiotic resistance genes.

    PubMed

    Moore, Aimée M; Patel, Sanket; Forsberg, Kevin J; Wang, Bin; Bentley, Gayle; Razia, Yasmin; Qin, Xuan; Tarr, Phillip I; Dantas, Gautam

    2013-01-01

    Emerging antibiotic resistance threatens human health. Gut microbes are an epidemiologically important reservoir of resistance genes (resistome), yet prior studies indicate that the true diversity of gut-associated resistomes has been underestimated. To deeply characterize the pediatric gut-associated resistome, we created metagenomic recombinant libraries in an Escherichia coli host using fecal DNA from 22 healthy infants and children (most without recent antibiotic exposure), and performed functional selections for resistance to 18 antibiotics from eight drug classes. Resistance-conferring DNA fragments were sequenced (Illumina HiSeq 2000), and reads assembled and annotated with the PARFuMS computational pipeline. Resistance to 14 of the 18 antibiotics was found in stools of infants and children. Recovered genes included chloramphenicol acetyltransferases, drug-resistant dihydrofolate reductases, rRNA methyltransferases, transcriptional regulators, multidrug efflux pumps, and every major class of beta-lactamase, aminoglycoside-modifying enzyme, and tetracycline resistance protein. Many resistance-conferring sequences were mobilizable; some had low identity to any known organism, emphasizing cryptic organisms as potentially important resistance reservoirs. We functionally confirmed three novel resistance genes, including a 16S rRNA methylase conferring aminoglycoside resistance, and two tetracycline-resistance proteins nearly identical to a bifidobacterial MFS transporter (B. longum s. longum JDM301). We provide the first report to our knowledge of resistance to folate-synthesis inhibitors conferred by a predicted Nudix hydrolase (part of the folate synthesis pathway). This functional metagenomic survey of gut-associated resistomes, the largest of its kind to date, demonstrates that fecal resistomes of healthy children are far more diverse than previously suspected, that clinically relevant resistance genes are present even without recent selective antibiotic

  20. 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.

  1. Resistance mutations generate divergent antibiotic susceptibility profiles against translation inhibitors

    PubMed Central

    Cocozaki, Alexis I.; Altman, Roger B.; Huang, Jian; Buurman, Ed T.; Kazmirski, Steven L.; Doig, Peter; Prince, D. Bryan; Blanchard, Scott C.; Cate, Jamie H. D.; Ferguson, Andrew D.

    2016-01-01

    Mutations conferring resistance to translation inhibitors often alter the structure of rRNA. Reduced susceptibility to distinct structural antibiotic classes may, therefore, emerge when a common ribosomal binding site is perturbed, which significantly reduces the clinical utility of these agents. The translation inhibitors negamycin and tetracycline interfere with tRNA binding to the aminoacyl-tRNA site on the small 30S ribosomal subunit. However, two negamycin resistance mutations display unexpected differential antibiotic susceptibility profiles. Mutant U1060A in 16S Escherichia coli rRNA is resistant to both antibiotics, whereas mutant U1052G is simultaneously resistant to negamycin and hypersusceptible to tetracycline. Using a combination of microbiological, biochemical, single-molecule fluorescence transfer experiments, and X-ray crystallography, we define the specific structural defects in the U1052G mutant 70S E. coli ribosome that explain its divergent negamycin and tetracycline susceptibility profiles. Unexpectedly, the U1052G mutant ribosome possesses a second tetracycline binding site that correlates with its hypersusceptibility. The creation of a previously unidentified antibiotic binding site raises the prospect of identifying similar phenomena in antibiotic-resistant pathogens in the future. PMID:27382179

  2. Antibiotic resistance mechanisms in M. tuberculosis: an update.

    PubMed

    Nguyen, Liem

    2016-07-01

    Treatment of tuberculosis (TB) has been a therapeutic challenge because of not only the naturally high resistance level of Mycobacterium tuberculosis to antibiotics but also the newly acquired mutations that confer further resistance. Currently standardized regimens require patients to daily ingest up to four drugs under direct observation of a healthcare worker for a period of 6-9 months. Although they are quite effective in treating drug susceptible TB, these lengthy treatments often lead to patient non-adherence, which catalyzes for the emergence of M. tuberculosis strains that are increasingly resistant to the few available anti-TB drugs. The rapid evolution of M. tuberculosis, from mono-drug-resistant to multiple drug-resistant, extensively drug-resistant and most recently totally drug-resistant strains, is threatening to make TB once again an untreatable disease if new therapeutic options do not soon become available. Here, I discuss the molecular mechanisms by which M. tuberculosis confers its profound resistance to antibiotics. This knowledge may help in developing novel strategies for weakening drug resistance, thus enhancing the potency of available antibiotics against both drug susceptible and resistant M. tuberculosis strains. PMID:27161440

  3. 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.

  4. Plasmids Carried by Antibiotic-Resistant Marine Bacteria

    PubMed Central

    Sizemore, Ronald K.; Colwell, R. R.

    1977-01-01

    Antibiotic-resistant bacteria were isolated from seawater samples collected in the Atlantic Ocean off the southeastern coast of the United States. Large numbers of antibiotic-resistant bacterial strains were found to be present in harbor and inshore waters; however, the percentage of resistant strains was higher for several seawater samples collected offshore than for those collected near shore. Bacteria resistant to tetracycline, chloramphenicol, and streptomycin were found in nearly all samples collected, including samples from 200 miles (about 522 km) offshore and at depths to 8,200 m. Sediment samples, in general, were found to contain smaller populations of resistant strains as compared with the seawater samples examined. Antibiotic-resistant bacteria exhibiting phenetic characteristics common to autochthonous marine bacterial species were examined in detail, and several of the isolates exhibited unstable antibiotic resistance, which was transferable to recipient Escherichia coli cells. Deoxyribonucleic acid preparations from 10 strains examined by ethidium bromide-cesium chloride density sedimentation revealed that 6 of the strains contained covalently closed circular plasmid deoxyribonucleic acid. PMID:334064

  5. 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.

  6. In tepid defense of population health: physicians and antibiotic resistance.

    PubMed

    Saver, Richard S

    2008-01-01

    Antibiotic resistance menaces the population as a dire public health threat and costly social problem. Recent proposals to combat antibiotic resistance focus to a large degree on supply side approaches. Suggestions include tinkering with patent rights so that pharmaceutical companies have greater incentives to discover novel antibiotics as well as to resist overselling their newer drugs already on market. This Article argues that a primarily supply side emphasis unfortunately detracts attention from physicians' important demand side influences. Physicians have a vital and unavoidably necessary role to play in ensuring socially optimal access to antibiotics. Dismayingly, physicians' management of the antibiotic supply has been poor and their defense of population health tepid at best. Acting as a prudent steward of the antibiotic supply often seems to be at odds with a physician's commonly understood fiduciary duties, ethical obligations, and professional norms, all of which traditionally emphasize the individual health paradigm as opposed to population health responsibilities. Meanwhile, physicians face limited incentives for antibiotic conservation from other sources, such as malpractice liability, regulatory standards, and reimbursement systems. While multifaceted efforts are needed to combat antibiotic resistance effectively, physician gatekeeping behavior should become a priority area of focus. This Article considers how health law and policy tools could favorably change the incentives physicians face for antibiotic conservation. A clear lesson from the managed care reform battles of the recent past is that interventions, to have the best chance of success, need to respect physician interest in clinical autonomy and individualized medicine even if, somewhat paradoxically, vigorously promoting population health perspectives. Also, physicians' legal and ethical obligations need to be reconceptualized in the antibiotic context in order to better support

  7. Occurrence of antibiotics and antibiotic resistances in soils from wastewater irrigation areas in Beijing and Tianjin, China.

    PubMed

    Chen, Chaoqi; Li, Jing; Chen, Peipei; Ding, Rui; Zhang, Pengfei; Li, Xiqing

    2014-10-01

    Non-irrigated and wastewater-irrigated soils were collected from five wastewater irrigation areas in Beijing and Tianjin, China. The concentrations of sulfadiazine, sulfamethoxazole, oxytetracycline and chlortetracycline in the soils were determined. Abundances of antibiotic resistant bacteria and corresponding resistance genes were also measured to examine the impact of wastewater irrigation. No significant difference in antibiotic resistance bacteria was observed between irrigated and non-irrigated soils. However, the concentrations of antibiotics and abundances of resistance genes were significantly greater in irrigated soils, indicating that agricultural activities enhanced the occurrence of antibiotics and resistance genes in the soils. In addition, no significant difference was observed between previously and currently wastewater-irrigated soils. Therefore, cessation of wastewater irrigation did not significantly reduce the levels of antibiotic concentrations and resistance gene abundances. Other factors, e.g., manure application, may explain the lack of significant difference in the occurrence of antibiotics and resistance genes between previously and currently wastewater-irrigated soils.

  8. 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.

  9. 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. PMID:25561178

  10. 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.

  11. Antibiotic Administration Routes Significantly Influence the Levels of Antibiotic Resistance in Gut Microbiota

    PubMed Central

    Zhang, Lu; Huang, Ying; Zhou, Yang; Buckley, Timothy

    2013-01-01

    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. PMID:23689712

  12. Plasmid Mediated Antibiotic Resistance in Isolated Bacteria From Burned Patients

    PubMed Central

    Beige, Fahimeh; Baseri Salehi, Majid; Bahador, Nima; Mobasherzadeh, Sina

    2014-01-01

    Background: Nowadays, the treatment of burned patients is difficult because of the high frequency of infection with antibiotic resistance bacteria. Objectives: This study was conducted to evaluate the level of antibiotic resistance in Gram-negative bacteria and its relation with the existence of plasmid. Materials and Methods: The samples were collected from two hundred twenty hospitalized burned patients in Isfahan burn hospital during a three-month period (March 2012 to June 2012). The samples were isolated and the Gram-negative bacteria were identified using phenotypic method and API 20E System. Antibiotic susceptibility and plasmid profile were determined by standard Agar disc diffusion and plasmid spin column extraction methods. Results: Totally 117 Gram-negative bacteria were isolated, the most common were Pseudomonas aerugionsa (37.6%), P. fluorescens (25.6%), Acinetobacter baumanii (20/5%) and Klebsiella pneumoniae (7.6%), respectively. The isolates showed high frequency of antibiotic resistance against ceftazidime and co-amoxiclave (100%) and low frequency of antibiotic resistance against amikacin with (70%).The results indicated that 60% of the isolates harboured plasmid. On the other hand, the patients infected with A. baumanii and P. aeruginosa were cured (with 60% frequency) whereas, those infected with P. fluorescens were not cured. Hence, probably antibiotic resistance markers of A. baumanii and P. aeruginosa are plasmid mediated; however, P. fluorescens is chromosomally mediated. Conclusions: Based on our findings, P. aerugionsa is a major causative agent of wound infections and amikacin could be considered as a more effective antibiotic for treatment of the burned patients. PMID:25789121

  13. Antibiotic resistance and antibiotic sensitivity based treatment in Helicobacter pylori infection: advantages and outcome

    PubMed Central

    Street, M; Caruana, P; Caffarelli, C; Magliani, W; Manfredi, M; Fornaroli, F; de'Angelis, G

    2001-01-01

    AIMS—To compare two strategies for the eradication of Helicobacter pylori infection.
METHODS—Groups 1 and 2 each consisted of 75 consecutive patients. Patients in group 1 were treated with two antibiotics based on antibiotic susceptibility testing; those in group 2 received amoxycillin and clarithromycin for eight days, together with either ranitidine or omeprazole. Eradication rate was assessed in both groups six months after treatment.
RESULTS—In group 1, H pylori grew in culture in 63/75 cases. Susceptibility testing showed that 35/63 isolates were resistant to metronidazole, 10/63 to clarithromycin, 2/63 to ampicillin, 1/63 to tetracycline, and 5/63 to both clarithromycin and metronidazole. In group 1the infection was eradicated in 96% of the initial 75 subjects, and in 98% of the subjects treated according to the antibiotic assay (62/63). As two patients were lost at follow up the overall eradication rate was 99%. In group 2, eradication was achieved in 61/75 subjects (81%). This was significantly lower than the percentage of eradication observed in group 1 (81% versus 99%).
CONCLUSIONS—Antibiotic susceptibility tests are useful in childhood as a very high percentage of subjects are cured. This approach is costly, but selective antibiotic treatment contributes to limit further development of antibiotic resistance, and money is saved in terms of reinvestigation and further repeated treatments.

 PMID:11316688

  14. Antibiotic resistance: challenges and successes in respiratory infection.

    PubMed

    Sethi, Sanjay; Bryan, Jenny

    2016-01-01

    European Respiratory Society Congress, Amsterdam, 26-30 September 2015, and CHEST 2015, Montréal, Canada, 24-28 October 2015 With approximately 50,000 deaths in the US and EU attributed to antibacterial resistance each year, together with several million days of hospital care [1], the need to address resistance mechanisms and find new targets for novel antibiotics has never been greater. At the annual congresses of the European Respiratory Society and the American College of Chest Physicians, presenters reported advances in understanding of the mechanisms of antibiotic resistance and how these may be overcome. The latest clinical trial data on antibiotic treatment for hospital- and community-acquired pneumonia, including the potential for novel nebulized forms of therapy, were also discussed. PMID:27081910

  15. 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.

  16. 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. PMID:19430071

  17. Removal of antibiotics and antibiotic resistance genes in rural wastewater by an integrated constructed wetland.

    PubMed

    Chen, Jun; Liu, You-Sheng; Su, Hao-Chang; Ying, Guang-Guo; Liu, Feng; Liu, Shuang-Shuang; He, Liang-Ying; Chen, Zhi-Feng; Yang, Yong-Qiang; Chen, Fan-Rong

    2015-02-01

    Integrated constructed wetlands (ICWs) are regarded as one of the most important removal technology for pollutants in rural domestic wastewaters. This study investigated the efficiency of an ICW consisting of a regulating pool, four surface and subsurface flow-constructed wetlands, and a stabilization unit for removing antibiotics and antibiotic resistance genes (ARGs) from rural domestic wastewaters. The results showed that antibiotics leucomycin, ofloxacin, lincomycin, and sulfamethazine, and ARGs sul1, sul2, tetM, and tetO were the predominant antibiotics and ARGs in the influent, respectively. The ICW system could significantly reduce most of the detected antibiotics and ARGs with their aqueous removal rates of 78 to 100 % and >99 %, respectively. Based on the measured concentrations, the total pollution loadings of antibiotics were 3,479 μg/day in the influent and 199 μg/day in the final effluent. Therefore, constructed wetlands could be a promising technology for rural wastewater in removing contaminants such as antibiotics and ARGs.

  18. Occurrence and prevalence of antibiotic resistance in landfill leachate.

    PubMed

    Wang, Yangqing; Tang, Wei; Qiao, Jing; Song, Liyan

    2015-08-01

    Antibiotic resistance (AR) is extensively present in various environments, posing emerging threat to public and environmental health. Landfill receives unused and unwanted antibiotics through household waste and AR within waste (e.g., activated sludge and illegal clinical waste) and is supposed to serve as an important AR reservoir. In this study, we used culture-dependent methods and quantitative molecular techniques to detect and quantify antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in 12 landfill leachate samples from six geographic different landfills, China. Five tested ARGs (tetO, tetW, bla(TEM), sulI, and sulII) and seven kinds of antibiotic-resistant heterotrophic ARB were extensively detected in all samples, demonstrating their occurrence in landfill. The detected high ratio (10(-2) to 10(-5)) of ARGs to 16S ribosomal RNA (rRNA) gene copies implied that ARGs are prevalent in landfill. Correlation analysis showed that ARGs (tetO, tetW, sulI, and sulII) significantly correlated to ambient bacterial 16S rRNA gene copies, suggesting that the abundance of bacteria in landfill leachate may play an important role in the horizontal spread of ARGs.

  19. Antibiotic Resistance in Enterococcus faecalis Isolated from Hospitalized Patients

    PubMed Central

    Balaei Gajan, Esrafil; Shirmohammadi, Adileh; Aghazadeh, Mohammad; Alizadeh, Mohammad; Sighari Deljavan, Alireza; Ahmadpour, Farzin

    2013-01-01

    Background and aims Enterococci are Gram-positive cocci that often occur in pairs (diplococci) or short chains. Be-side developing high level of antibiotic resistance, these bacteria can cause wide range of disease in human, thus to help provide an effective treatment for infections caused by this genus, this study was conceived to provide information on Enterococcus faecalis Antibiotic resistance to widely used antibiotics in hospitalized patients. Materials and methods Disk diffusion agar and Broth dilution methods were used to perform Antibiogram test on isolated Enterococcus faecalis. Culture medium used for Disk diffusion agar test was Muller Hinton agar, and for Broth dilution methods, Muller Hinton broth culture medium was utilized. In disk diffusion agar method, different commercial antibiotics disks produced by Pharmaceutical companies were used. Microsoft Excel software was used to perform statistical analysis. Results Based on antibiograms of 105 cases, a high resistance to Synercid, Nalidixic acid, Oxacillin and Teofilin was de-tected whereas the lowest resistance observed in Nitrofurantoin, Vancomycin, Linezolid and Teicoplanin antibiotics. Conclusion According to the results, Teicoplanin, Vancomycin, Linezolid and Nitrofurantoin are recommended against E. faecalis species. PMID:23875089

  20. Epidemiological Interpretation of Studies Examining the Effect of Antibiotic Usage on Resistance

    PubMed Central

    Schechner, Vered; Temkin, Elizabeth; Harbarth, Stephan; Carmeli, Yehuda

    2013-01-01

    SUMMARY Bacterial resistance to antibiotics is a growing clinical problem and public health threat. Antibiotic use is a known risk factor for the emergence of antibiotic resistance, but demonstrating the causal link between antibiotic use and resistance is challenging. This review describes different study designs for assessing the association between antibiotic use and resistance and discusses strengths and limitations of each. Approaches to measuring antibiotic use and antibiotic resistance are presented. Important methodological issues such as confounding, establishing temporality, and control group selection are examined. PMID:23554418

  1. 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

  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. PMID:27236477

  3. Consolidating and Exploring Antibiotic Resistance Gene Data Resources.

    PubMed

    Xavier, Basil Britto; Das, Anupam J; Cochrane, Guy; De Ganck, Sandra; Kumar-Singh, Samir; Aarestrup, Frank Møller; Goossens, Herman; Malhotra-Kumar, Surbhi

    2016-04-01

    The unrestricted use of antibiotics has resulted in rapid acquisition of antibiotic resistance (AR) and spread of multidrug-resistant (MDR) bacterial pathogens. With the advent of next-generation sequencing technologies and their application in understanding MDR pathogen dynamics, it has become imperative to unify AR gene data resources for easy accessibility for researchers. However, due to the absence of a centralized platform for AR gene resources, availability, consistency, and accuracy of information vary considerably across different databases. In this article, we explore existing AR gene data resources in order to make them more visible to the clinical microbiology community, to identify their limitations, and to propose potential solutions.

  4. Consolidating and Exploring Antibiotic Resistance Gene Data Resources

    PubMed Central

    Xavier, Basil Britto; Das, Anupam J.; Cochrane, Guy; De Ganck, Sandra; Kumar-Singh, Samir; Aarestrup, Frank Møller; Goossens, Herman

    2016-01-01

    The unrestricted use of antibiotics has resulted in rapid acquisition of antibiotic resistance (AR) and spread of multidrug-resistant (MDR) bacterial pathogens. With the advent of next-generation sequencing technologies and their application in understanding MDR pathogen dynamics, it has become imperative to unify AR gene data resources for easy accessibility for researchers. However, due to the absence of a centralized platform for AR gene resources, availability, consistency, and accuracy of information vary considerably across different databases. In this article, we explore existing AR gene data resources in order to make them more visible to the clinical microbiology community, to identify their limitations, and to propose potential solutions. PMID:26818666

  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. Impact of antibiotic resistance on the treatment of sepsis.

    PubMed

    Turnidge, John

    2003-01-01

    Antibiotics are essential to the treatment of bacterial sepsis as they reduce the bacterial burden. The impact of bacterial resistance has recently been studied and found to be important in a range of conditions. Resistance to antibiotics can be defined genotypically, phenotypically and clinically through pharmacokinetic/pharmacodynamic studies and their correlations with clinical outcomes. Although the kinetics of antibiotics has been shown to be favourably altered in sepsis, a range of studies in sepsis has revealed that for most pathogens resistance contributes to significant increases in mortality. This has been clearly demonstrated in bacteraemia, including community- and hospital-acquired infection, and with bacteraemia caused by vancomycin-resistant enterococci, methicillin-resistant staphylococci and extended-spectrum producing Gram-negative bacteria. Significant mortality increases have also been seen with ventilator-associated pneumonia and serious infections requiring admission to intensive care. Gentotypic and phenotypic resistance in coagulase-negative staphylococci causing bacteraemia, and in invasive pneumococcal disease has not shown differences in mortality. In the latter case, dosage regimens have to date been adequate to overcome laboratory-defined resistance. Early indications are that de-escalating therapy from broad-spectrum initial coverage after results of cultures and susceptibility tests become available does not jeopardize outcomes, and further prospective studies are warranted. There is now convincing evidence that broad-spectrum initial therapy to cover the likely pathogens and their resistances pending culture results is mandatory in sepsis to minimize adverse outcomes.

  7. 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

  8. Relationships between antibiotics and antibiotic resistance gene levels in municipal solid waste leachates in Shanghai, China.

    PubMed

    Wu, Dong; Huang, Zhiting; Yang, Kai; Graham, David; Xie, Bing

    2015-04-01

    Many studies have quantified antibiotics and antibiotic resistance gene (ARG) levels in soils, surface waters, and waste treatment plants (WTPs). However, similar work on municipal solid waste (MSW) landfill leachates is limited, which is concerning because antibiotics disposal is often in the MSW stream. Here we quantified 20 sulfonamide (SA), quinolone (FQ), tetracycline (TC), macrolide (ML), and chloramphenicol (CP) antibiotics, and six ARGs (sul1, sul2, tetQ, tetM, ermB, and mefA) in MSW leachates from two Shanghai transfer stations (TS; sites Hulin (HL) and Xupu (XP)) and one landfill reservoir (LR) in April and July 2014. Antibiotic levels were higher in TS than LR leachates (985 ± 1965 ng/L vs 345 ± 932 ng/L, n = 40), which was because of very high levels in the HL leachates (averaging at 1676 ± 5175 ng/L, n = 40). The mean MLs (3561 ± 8377 ng/L, n = 12), FQs (975 ± 1608 ng/L, n = 24), and SAs (402 ± 704 ng/L, n = 42) classes of antibiotics were highest across all samples. ARGs were detected in all leachate samples with normalized sul2 and ermB levels being especially elevated (-1.37 ± 1.2 and -1.76 ± 1.6 log (copies/16S-rDNA), respectively). However, ARG abundances did not correlate with detected antibiotic levels, except for tetW and tetQ with TC levels (r = 0.88 and 0.81, respectively). In contrast, most measured ARGs did significantly correlate with heavy metal levels (p < 0.05), especially with Cd and Cr. This study shows high levels of ARGs and antibiotics can prevail in MSW leachates and landfills may be an underappreciated as a source of antibiotics and ARGs to the environment.

  9. 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

  10. The Association of Age and Antibiotic Resistance of Helicobacter Pylori

    PubMed Central

    Ji, Zizhong; Han, Feng; Meng, Fei; Tu, Miaoying; Yang, Ningmin; Zhang, Jianzhong

    2016-01-01

    Abstract The antibiotic resistance of Helicobacter pylori (H pylori) is steadily increasing worldwide, resulting in the low efficiency of the current therapeutic approaches for eradication. In this study, we investigated the relationship between antibiotic resistances, the year of sample collection, and the ages of the infected individuals. A total of 29,034 gastric mucosa biopsy samples were randomly collected from January 1, 2009 to December 9, 2014 in Jiaxing City, Zhejiang Province, China. An antibiotic susceptibility testing was determined using an agar-dilution method. The statistical significance was tested using the chi-squared (χ2) test. A total of 9687 strains were isolated. The resistance rate to clarithromycin, levofloxacin, and metronidazole were 17.76%, 19.66%, and 95.5%, respectively. Resistance was rare against amoxicillin, gentamicin, and furazolidone. The metronidazole resistance rate stayed at a consistently high level. In contrast, the resistance rates of clarithromycin and levofloxacin increased rapidly from 2009 to 2011, gradually decreased from 2012 to 2013, and then increased again in 2014. Although patients ages 31 to 50 and 71 to 80 years had lower infection rates of H pylori, they also had higher resistance rates to clarithromycin and levofloxacin. The highest antibiotic resistance rate was observed in patients’ ages 71 to 80 years old. Younger patients (below 30 years old) had a lower resistance to levofloxacin. Patients’ ages 51 to 60 years old may thus represent an important category for the future study of H pylori infection. Age plays a key element in H pylori resistance to clarithromycin and levofloxacin. It is therefore necessary to consider individualized therapy for the optimized treatment of H pylori-infected patients. PMID:26937912

  11. 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.

  12. 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. PMID:24129283

  13. Association of mercury resistance with antibiotic resistance in the gram-negative fecal bacteria of primates.

    PubMed Central

    Wireman, J; Liebert, C A; Smith, T; Summers, A O

    1997-01-01

    Gram-negative fecal bacterial from three longitudinal Hg exposure experiments and from two independent survey collections were examined for their carriage of the mercury resistance (mer) locus. The occurrence of antibiotic resistance was also assessed in both mercury-resistant (Hgr) and mercury-susceptible (Hgs) isolates from the same collections. The longitudinal studies involved exposure of the intestinal flora to Hg released from amalgam "silver" dental restorations in six monkeys. Hgr strains were recovered before the installation of amalgams, and frequently these became the dominant strains while amalgams were installed. Such persistent Hgr strains always carried the same mer locus throughout the experiments. In both the longitudinal and survey collections, certain mer loci were preferentially associated with one genus, whereas other mer loci were recovered from many genera. In general, strains with any mer locus were more likely to be multiresistant than were strains without mer loci; this clustering tendency was also seen for antibiotic resistance genes. However, the association of antibiotic multiresistance with mer loci was not random; regardless of source, certain mer loci occurred in highly multiresistant strains (with as many as seven antibiotic resistances), whereas other mer loci were found in strains without any antibiotic resistance. The majority of highly multiresistant Hgr strains also carried genes characteristic of an integron, a novel genetic element which enables the formation of tandem arrays of antibiotic resistance genes. Hgr strains lacking antibiotic resistance showed no evidence of integron components. PMID:9361435

  14. 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.

  15. 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. PMID:16753197

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

    PubMed Central

    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. PMID:25972842

  17. 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. PMID:27620952

  18. 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

  19. 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. PMID:27416310

  20. 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

  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. Characterization of antibiotic resistance determinants in oral biofilms.

    PubMed

    Kim, Seon-Mi; Kim, Hyeong C; Lee, Seok-Woo S

    2011-08-01

    Oral biofilms contain numerous antibiotic resistance determinants that can be transferred within or outside of the oral cavity. The aim of this study was to evaluate the prevalence and the relative level of antibiotic resistance determinants from oral biofilms. Oral biofilm samples that were collected from healthy subjects and periodontitis patients were subjected to qualitative and quantitative analyses for selected antibiotic resistance determinants using PCR. The prevalence of tet(Q), tet(M), cfxA, and bla ( TEM ) was very high both in the patient and the healthy subject group, with a tendency toward higher values in the patient group, with the exception of erm(F), which was more prevalent in the healthy group. The two extended spectrum β-lactam (ESBL) resistance determinants bla ( SHV ) and bla ( TEM ) showed a dramatic difference, as bla ( TEM ) was present in all of the samples and bla ( SHV ) was not found at all. The aacA-aphD, vanA, and mecA genes were rarely detected, suggesting that they are not common in oral bacteria. A quantitative PCR analysis showed that the relative amount of resistance determinants present in oral biofilms of the patient group was much greater than that of the healthy group, exhibiting 17-, 13-, 145-, and 3-fold increases for tet(Q), tet(M), erm(F), and cfxA, respectively. The results of this study suggest that the oral antibiotic resistome is more diverse and abundant in periodontitis patients than in healthy subjects, suggesting that there is a difference in the diversity and distribution of antibiotic resistance in oral biofilms associated with health and disease.

  3. 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. PMID:21821757

  4. The antibiotic resistance crisis: part 1: causes and threats.

    PubMed

    Ventola, C Lee

    2015-04-01

    Decades after the first patients were treated with antibiotics, bacterial infections have again become a threat because of the rapid emergence of resistant bacteria-a crisis attributed to abuse of these medications and a lack of new drug development. PMID:25859123

  5. 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…

  6. Risk of antibiotic resistance from metal contaminated soils

    NASA Astrophysics Data System (ADS)

    Knapp, Charles

    2013-04-01

    It is known that contaminated soils can lead to increased incidence of illness and disease, but it may also prevent our ability to fight disease. Many antibiotic resistant genes (ARG) acquired by bacteria originate from the environment. It is important to understand factors that influence levels of ARG in the environment, which could affect us clinically and agriculturally. The presence of elevated metal content in soils often promotes antibiotic resistance in exposed microorganisms. Using qPCR, the abundances of ARG to compare levels with geochemical conditions in randomly selected soils from several countries. Many ARG positively correlated with soil metal content, especially copper, chromium, nickel, lead, and iron. Results suggest that geochemical metal conditions influence the potential for antibiotic resistance in soil, which might be used to estimate baseline gene presence on various landscape scales and may translate to epidemiological risk of antibiotic-resistance transmission from the environment. This suggests that we may have to reconsider tolerances of metal pollution in the environment.

  7. 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...

  8. 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…

  9. 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.

  10. 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. PMID:25662190

  11. 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.

  12. 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.

  13. Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications.

    PubMed

    Iredell, Jon; Brown, Jeremy; Tagg, Kaitlin

    2016-02-08

    Resistance of the Enterobacteriaceae to antibiotics, especially of the β lactam type, is increasingly dominated by the mobilization of continuously expressed single genes that encode efficient drug modifying enzymes. Strong and ubiquitous selection pressure has seemingly been accompanied by a shift from "natural" resistance, such as inducible chromosomal enzymes, membrane impermeability, and drug efflux, to the modern paradigm of mobile gene pools that largely determine the epidemiology of modern antibiotic resistance. In this way, antibiotic resistance is more available than ever before to organisms such as Escherichia coli and Klebsiella pneumoniae that are important causes of major sepsis. Modulation of the phenotype by host bacteria makes gene transmission less obvious and may in part explain why tracking and control of carbapenem resistance has been particularly problematic in the Enterobacteriaceae. This review discusses the underlying principles and clinical implications of the mobility and fixation of resistance genes and the exploitable opportunities and potential threats arising from apparent limitations on diversity in these mobile gene pools. It also provides some illustrative paradoxes and clinical corollaries, as well as a summary of future options.

  14. [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.

  15. 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

  16. 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.

  17. 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.

  18. Insights on Virulence and Antibiotic Resistance: A Review of the Accessory Genome of Staphylococcus aureus.

    PubMed

    Shittu, Adebayo O; Udo, Edet E; Lin, Johnson

    2007-09-01

    Staphylococcus aureus continues to be a serious health problem worldwide due to its intrinsic nature of virulence, ability to cause a wide array of infection, and its capacity to develop resistance to a number of antibiotics. The S aureus genome has continually evolved through both mutation and acquisition of exogenous genes, leading to the emergence of antibiotic-resistant strains with the ability for clonal dissemination across nations and continents. Methicillin-resistant S aureus (MRSA) is one of the most commonly identified antibiotic-resistant pathogens in the hospital and community settings with substantial mortality and morbidity. This review examines the accessory genome of 8 sequenced S aureus strains regarding the variety of virulence factors and mechanisms of antibiotic resistance. The remarkable nature of this organism to acquire and disseminate an array of mobile genetic elements (MBEs) through horizontal gene transfer illustrates the mechanisms for evolution and its fitness level in the face of constant environmental challenges. The relative ease of transfer of genetic materials, especially antibiotic-resistant genes, across staphylococcal species indicates that there is a potential pandemic problem in the hospital and community environment.

  19. 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.

  20. Oral Antibiotics are Effective for Highly Resistant Hip Arthroplasty Infections

    PubMed Central

    Esteban, Jaime; García-Cimbrelo, Eduardo

    2009-01-01

    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. Level of Evidence: Level IV, prognostic study. See Guidelines for Authors for a complete description of levels of evidence. PMID:19333670

  1. 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...

  2. 2nd U.S. Case of Bacteria Resistant to Last-Resort Antibiotic

    MedlinePlus

    ... news/fullstory_159807.html 2nd U.S. Case of Bacteria Resistant to Last-Resort Antibiotic Scientists concerned it ... the United States who was infected with a bacteria that is resistant to an antibiotic of last ...

  3. Antibiotic resistance in Providencia stuartii isolated in hospitals.

    PubMed Central

    McHale, P J; Keane, C T; Dougan, G

    1981-01-01

    A total of 238 isolates of Providencia stuartii obtained from infected patients in six Dublin hospitals were grouped by using serological and bacteriocin typing methods and tested for sensitivity to a number of antimicrobial agents. Most isolates were resistant to several of these agents. Resistance to tetracycline, resistance to penicillin, resistance to polymyxin, and probably resistance to nitrofurantoin was intrinsic. Plasmid screening coupled with resistance transfer studies showed that both chromosome-encoded and plasmid-coded resistance mechanisms were clinically important. Ampicillin resistance was both chromosomally and plasmid encoded, whereas resistance to kanamycin and resistance to carbenicillin were exclusively plasmid encoded. Gentamicin resistance was more common than kanamycin resistance, and although gentamicin-resistant strains contained aminoglycoside acetyltransferase activity, no association could be demonstrated with plasmid deoxyribonucleic acid in the strains tested. Unlike minimal inhibitory concentrations for kanamycin, minimal inhibitory concentrations for gentamicin varied over a wide range. P. stuartii isolated obtained from several different countries were tested for comparison. As a group, these strains were less resistant, but they did exhibit similar resistance properties. Images PMID:7251830

  4. Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria.

    PubMed

    Yosef, Ido; Manor, Miriam; Kiro, Ruth; Qimron, Udi

    2015-06-01

    The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. Here we present a proof of concept for a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. We use temperate phages to deliver a functional clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) system into the genome of antibiotic-resistant bacteria. The delivered CRISPR-Cas system destroys both antibiotic resistance-conferring plasmids and genetically modified lytic phages. This linkage between antibiotic sensitization and protection from lytic phages is a key feature of the strategy. It allows programming of lytic phages to kill only antibiotic-resistant bacteria while protecting antibiotic-sensitized bacteria. Phages designed according to this strategy may be used on hospital surfaces and hand sanitizers to facilitate replacement of antibiotic-resistant pathogens with sensitive ones. PMID:26060300

  5. Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria.

    PubMed

    Yosef, Ido; Manor, Miriam; Kiro, Ruth; Qimron, Udi

    2015-06-01

    The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. Here we present a proof of concept for a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. We use temperate phages to deliver a functional clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) system into the genome of antibiotic-resistant bacteria. The delivered CRISPR-Cas system destroys both antibiotic resistance-conferring plasmids and genetically modified lytic phages. This linkage between antibiotic sensitization and protection from lytic phages is a key feature of the strategy. It allows programming of lytic phages to kill only antibiotic-resistant bacteria while protecting antibiotic-sensitized bacteria. Phages designed according to this strategy may be used on hospital surfaces and hand sanitizers to facilitate replacement of antibiotic-resistant pathogens with sensitive ones.

  6. Temperate and lytic bacteriophages programmed to sensitize and kill antibiotic-resistant bacteria

    PubMed Central

    Yosef, Ido; Manor, Miriam; Kiro, Ruth

    2015-01-01

    The increasing threat of pathogen resistance to antibiotics requires the development of novel antimicrobial strategies. Here we present a proof of concept for a genetic strategy that aims to sensitize bacteria to antibiotics and selectively kill antibiotic-resistant bacteria. We use temperate phages to deliver a functional clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) system into the genome of antibiotic-resistant bacteria. The delivered CRISPR-Cas system destroys both antibiotic resistance-conferring plasmids and genetically modified lytic phages. This linkage between antibiotic sensitization and protection from lytic phages is a key feature of the strategy. It allows programming of lytic phages to kill only antibiotic-resistant bacteria while protecting antibiotic-sensitized bacteria. Phages designed according to this strategy may be used on hospital surfaces and hand sanitizers to facilitate replacement of antibiotic-resistant pathogens with sensitive ones. PMID:26060300

  7. 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

  8. Cultures of resistance? A Bourdieusian analysis of doctors' antibiotic prescribing.

    PubMed

    Broom, Alex; Broom, Jennifer; Kirby, Emma

    2014-06-01

    The prospect of an 'antimicrobial perfect storm' in the coming decades through the emergence and proliferation of multi-resistant organisms has become an urgent public health concern. With limited drug discovery solutions foreseeable in the immediate future, and with evidence that resistance can be ameliorated by optimisation of prescribing, focus currently centres on antibiotic use. In hospitals, this is manifest in the development of stewardship programs that aim to alter doctors' prescribing behaviour. Yet, in many clinical contexts, doctors' antibiotic prescribing continues to elude best practice. In this paper, drawing on qualitative interviews with 30 Australian hospital-based doctors in mid-2013, we draw on Bourdieu's theory of practice to illustrate that 'sub-optimal' antibiotic prescribing is a logical choice within the habitus of the social world of the hospital. That is, the rules of the game within the field are heavily weighted in favour of the management of immediate clinical risks, reputation and concordance with peer practice vis-à-vis longer-term population consequences. Antimicrobial resistance is thus a principal of limited significance in the hospital. We conclude that understanding the habitus of the hospital and the logics underpinning practice is a critical step toward developing governance practices that can respond to clinically 'sub-optimal' antibiotic use.

  9. 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.

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

    PubMed

    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

  11. The Ocean as a Global Reservoir of Antibiotic Resistance Genes

    PubMed Central

    Hatosy, Stephen M.

    2015-01-01

    Recent studies of natural environments have revealed vast genetic reservoirs of antibiotic resistance (AR) genes. Soil bacteria and human pathogens share AR genes, and AR genes have been discovered in a variety of habitats. However, there is little knowledge about the presence and diversity of AR genes in marine environments and which organisms host AR genes. To address this, we identified the diversity of genes conferring resistance to ampicillin, tetracycline, nitrofurantoin, and sulfadimethoxine in diverse marine environments using functional metagenomics (the cloning and screening of random DNA fragments). Marine environments were host to a diversity of AR-conferring genes. Antibiotic-resistant clones were found at all sites, with 28% of the genes identified as known AR genes (encoding beta-lactamases, bicyclomycin resistance pumps, etc.). However, the majority of AR genes were not previously classified as such but had products similar to proteins such as transport pumps, oxidoreductases, and hydrolases. Furthermore, 44% of the genes conferring antibiotic resistance were found in abundant marine taxa (e.g., Pelagibacter, Prochlorococcus, and Vibrio). Therefore, we uncovered a previously unknown diversity of genes that conferred an AR phenotype among marine environments, which makes the ocean a global reservoir of both clinically relevant and potentially novel AR genes. PMID:26296734

  12. 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

  13. 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

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

    PubMed

    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.

  15. Antibiotic resistance in an in vitro subgingival biofilm model

    PubMed Central

    Sedlacek, M. J.; Walker, C.

    2007-01-01

    Introduction: The purpose of this study was to utilize an in vitro biofilm model of subgingival plaque to investigate resistances in subgingival biofilm communities to antibiotics commonly used as adjuncts to periodontal therapy. Methods: Biofilms were grown on saliva-coated hydroxyapatite supports in trypticasesoy broth for 4 h–10 days and then exposed for 48 h to either increasing twofold concentrations of tetracycline, amoxicillin, clindamycin, and erythromycin or therapeutically achievable concentrations of tetracycline, doxycycline, minocycline, amoxicillin, metronidazole, amoxicillin/clavulanate, and amoxicillin/metronidazole. Results: Concentrations necessary to inhibit bacterial strains in steady-state biofilms were up to 250 times greater than the concentrations needed to inhibit the same strains grown planktonically. In the presence of therapeutically available antibiotic concentrations, significantly higher proportions of the biofilms remained viable as the biofilms reached steady-state growth. The combinations of amoxicillin/clavulanate and amoxicillin/metronidazole were the most effective in suppressing growth. These combinations were particularly effective against biofilms up to and including 7 days of age and inhibited 90% or more of the bacteria present relative to untreated controls. As the biofilms approached steady state, these combinations were less effective with 50−60% of the bacteria retaining viability. Conclusion: Most, but not all, species of subgingival bacteria are considerably more resistant in biofilms than in planktonic cultures. Resistance appeared to be age-related because biofilms demonstrated progressive antibiotic resistance as they matured with maximum resistance coinciding with the steady-state phase of biofilm growth. PMID:17803631

  16. Rapid electrochemical phenotypic profiling of antibiotic-resistant bacteria.

    PubMed

    Besant, Justin D; Sargent, Edward H; Kelley, Shana O

    2015-07-01

    Rapid phenotyping of bacteria to identify drug-resistant strains is an important capability for the treatment and management of infectious disease. At present, the rapid determination of antibiotic susceptibility is hindered by the requirement that, in existing devices, bacteria must be pre-cultured for 2-3 days to reach detectable levels. Here we report a novel electrochemical approach that achieves rapid readout of the antibiotic susceptibility profile of a bacterial infection within one hour. The electrochemical reduction of a redox-active molecule is monitored that reports on levels of metabolically-active bacteria. Bacteria are captured in miniaturized wells, incubated with antimicrobials and monitored for resistance. This electrochemical phenotyping approach is effective with clinically-relevant levels of bacteria, and provides results comparable to culture-based analysis. Results, however, are delivered on a much faster timescale, with resistance profiles available after a one hour incubation period.

  17. Costs of antibiotic resistance - separating trait effects and selective effects.

    PubMed

    Hall, Alex R; Angst, Daniel C; Schiessl, Konstanze T; Ackermann, Martin

    2015-03-01

    Antibiotic resistance can impair bacterial growth or competitive ability in the absence of antibiotics, frequently referred to as a 'cost' of resistance. Theory and experiments emphasize the importance of such effects for the distribution of resistance in pathogenic populations. However, recent work shows that costs of resistance are highly variable depending on environmental factors such as nutrient supply and population structure, as well as genetic factors including the mechanism of resistance and genetic background. Here, we suggest that such variation can be better understood by distinguishing between the effects of resistance mechanisms on individual traits such as growth rate or yield ('trait effects') and effects on genotype frequencies over time ('selective effects'). We first give a brief overview of the biological basis of costs of resistance and how trait effects may translate to selective effects in different environmental conditions. We then review empirical evidence of genetic and environmental variation of both types of effects and how such variation may be understood by combining molecular microbiological information with concepts from evolution and ecology. Ultimately, disentangling different types of costs may permit the identification of interventions that maximize the cost of resistance and therefore accelerate its decline.

  18. 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.

  19. Adaptive resistance to antibiotics in bacteria: a systems biology perspective.

    PubMed

    Sandoval-Motta, Santiago; Aldana, Maximino

    2016-05-01

    Despite all the major breakthroughs in antibiotic development and treatment procedures, there is still no long-term solution to the bacterial antibiotic resistance problem. Among all the known types of resistance, adaptive resistance (AdR) is particularly inconvenient. This phenotype is known to emerge as a consequence of concentration gradients, as well as contact with subinhibitory concentrations of antibiotics, both known to occur in human patients and livestock. Moreover, AdR has been repeatedly correlated with the appearance of multidrug resistance, although the biological processes behind its emergence and evolution are not well understood. Epigenetic inheritance, population structure and heterogeneity, high mutation rates, gene amplification, efflux pumps, and biofilm formation have all been reported as possible explanations for its development. Nonetheless, these concepts taken independently have not been sufficient to prevent AdR's fast emergence or to predict its low stability. New strains of resistant pathogens continue to appear, and none of the new approaches used to kill them (mixed antibiotics, sequential treatments, and efflux inhibitors) are completely efficient. With the advent of systems biology and its toolsets, integrative models that combine experimentally known features with computational simulations have significantly improved our understanding of the emergence and evolution of the adaptive-resistant phenotype. Apart from outlining these findings, we propose that one of the main cornerstones of AdR in bacteria, is the conjunction of two types of mechanisms: one rapidly responding to transient environmental challenges but not very efficient, and another much more effective and specific, but developing on longer time scales. WIREs Syst Biol Med 2016, 8:253-267. doi: 10.1002/wsbm.1335 For further resources related to this article, please visit the WIREs website. PMID:27103502

  20. Adaptive resistance to antibiotics in bacteria: a systems biology perspective.

    PubMed

    Sandoval-Motta, Santiago; Aldana, Maximino

    2016-05-01

    Despite all the major breakthroughs in antibiotic development and treatment procedures, there is still no long-term solution to the bacterial antibiotic resistance problem. Among all the known types of resistance, adaptive resistance (AdR) is particularly inconvenient. This phenotype is known to emerge as a consequence of concentration gradients, as well as contact with subinhibitory concentrations of antibiotics, both known to occur in human patients and livestock. Moreover, AdR has been repeatedly correlated with the appearance of multidrug resistance, although the biological processes behind its emergence and evolution are not well understood. Epigenetic inheritance, population structure and heterogeneity, high mutation rates, gene amplification, efflux pumps, and biofilm formation have all been reported as possible explanations for its development. Nonetheless, these concepts taken independently have not been sufficient to prevent AdR's fast emergence or to predict its low stability. New strains of resistant pathogens continue to appear, and none of the new approaches used to kill them (mixed antibiotics, sequential treatments, and efflux inhibitors) are completely efficient. With the advent of systems biology and its toolsets, integrative models that combine experimentally known features with computational simulations have significantly improved our understanding of the emergence and evolution of the adaptive-resistant phenotype. Apart from outlining these findings, we propose that one of the main cornerstones of AdR in bacteria, is the conjunction of two types of mechanisms: one rapidly responding to transient environmental challenges but not very efficient, and another much more effective and specific, but developing on longer time scales. WIREs Syst Biol Med 2016, 8:253-267. doi: 10.1002/wsbm.1335 For further resources related to this article, please visit the WIREs website.

  1. Plasmids in antibiotic susceptible and antibiotic resistant commensal Escherichia coli from healthy Australian adults.

    PubMed

    Moran, Robert A; Anantham, Sashindran; Pinyon, Jeremy L; Hall, Ruth M

    2015-07-01

    A collection of 111 commensal Escherichia coli isolated from 84 faecal samples from healthy Australian adults were screened using PCR-based replicon typing. Each isolate represented a distinct strain found in a particular faecal sample. Fifty-one isolates were resistant to one or more of 12 antibiotics tested. FII and FIB replicons were most common and usually found together. The FII replicon was detected in 63 isolates (35 susceptible, 28 resistant), the FIB replicon was present in 65 (32 susceptible, 33 resistant) and 54 (30 susceptible, 24 resistant) included both. Other replicon types were found infrequently (A/C, I1, K, L/M, P, R, Y, FIA and FIC) or not at all (HI1, HI2, N, T, U, W, X). Only the B/O amplicon, found in 21 resistant but only 4 susceptible isolates, was associated with antibiotic resistance. Detailed analysis of this group revealed that the B/O PCR also detected Z plasmids of several distinguishable types. PCR assays were developed to detect the two repA genes (repABKI and repAZ) found in members of the I-complex (I, B/O, K and Z plasmids). These assays distinguished the B/O and Z plasmids detected by the original "B/O" PCR. One isolate carried repABKI and the remainder carried repAZ. These genes were also detected in further isolates in the collection. Conjugative transfer of resistance genes was detected for the B/O plasmid and two Z groups. Evidence for transfer of repAZ plasmids in the human colon in the absence of antibiotic selection was also obtained.

  2. 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…

  3. Current perspectives on the dynamics of antibiotic resistance in different reservoirs.

    PubMed

    Caniça, Manuela; Manageiro, Vera; Jones-Dias, Daniela; Clemente, Lurdes; Gomes-Neves, Eduarda; Poeta, Patrícia; Dias, Elsa; Ferreira, Eugénia

    2015-09-01

    Antibiotic resistance consists of a dynamic web. In this review, we describe the path by which different antibiotic residues and antibiotic resistance genes disseminate among relevant reservoirs (human, animal, and environmental settings), evaluating how these events contribute to the current scenario of antibiotic resistance. The relationship between the spread of resistance and the contribution of different genetic elements and events is revisited, exploring examples of the processes by which successful mobile resistance genes spread across different niches. The importance of classic and next generation molecular approaches, as well as action plans and policies which might aid in the fight against antibiotic resistance, are also reviewed. PMID:26247891

  4. Parallel Mapping of Antibiotic Resistance Alleles in Escherichia coli

    PubMed Central

    Mortazavi, Pooneh; Knight, Rob; Gill, Ryan T.

    2016-01-01

    Chemical genomics expands our understanding of microbial tolerance to inhibitory chemicals, but its scope is often limited by the throughput of genome-scale library construction and genotype-phenotype mapping. Here we report a method for rapid, parallel, and deep characterization of the response to antibiotics in Escherichia coli using a barcoded genome-scale library, next-generation sequencing, and streamlined bioinformatics software. The method provides quantitative growth data (over 200,000 measurements) and identifies contributing antimicrobial resistance and susceptibility alleles. Using multivariate analysis, we also find that subtle differences in the population responses resonate across multiple levels of functional hierarchy. Finally, we use machine learning to identify a unique allelic and proteomic fingerprint for each antibiotic. The method can be broadly applied to tolerance for any chemical from toxic metabolites to next-generation biofuels and antibiotics. PMID:26771672

  5. 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.

  6. Old and New Glycopeptide Antibiotics: Action and Resistance

    PubMed Central

    Binda, Elisa; Marinelli, Flavia; Marcone, Giorgia Letizia

    2014-01-01

    Glycopeptides are considered antibiotics of last resort for the treatment of life-threatening infections caused by relevant Gram-positive human pathogens, such as Staphylococcus aureus, Enterococcus spp. and Clostridium difficile. The emergence of glycopeptide-resistant clinical isolates, first among enterococci and then in staphylococci, has prompted research for second generation glycopeptides and a flurry of activity aimed at understanding resistance mechanisms and their evolution. Glycopeptides are glycosylated non-ribosomal peptides produced by a diverse group of soil actinomycetes. They target Gram-positive bacteria by binding to the acyl-d-alanyl-d-alanine (d-Ala-d-Ala) terminus of the growing peptidoglycan on the outer surface of the cytoplasmatic membrane. Glycopeptide-resistant organisms avoid such a fate by replacing the d-Ala-d-Ala terminus with d-alanyl-d-lactate (d-Ala-d-Lac) or d-alanyl-d-serine (d-Ala-d-Ser), thus markedly reducing antibiotic affinity for the cellular target. Resistance has manifested itself in enterococci and staphylococci largely through the expression of genes (named van) encoding proteins that reprogram cell wall biosynthesis and, thus, evade the action of the antibiotic. These resistance mechanisms were most likely co-opted from the glycopeptide producing actinomycetes, which use them to avoid suicide during antibiotic production, rather than being orchestrated by pathogen bacteria upon continued treatment. van-like gene clusters, similar to those described in enterococci, were in fact identified in many glycopeptide-producing actinomycetes, such as Actinoplanes teichomyceticus, which produces teicoplanin, and Streptomyces toyocaensis, which produces the A47934 glycopeptide. In this paper, we describe the natural and semi-synthetic glycopeptide antibiotics currently used as last resort drugs for Gram-positive infections and compare the van gene-based strategies of glycopeptide resistance among the pathogens and the producing

  7. 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. PMID:25541089

  8. Delayed commitment to evolutionary fate in antibiotic resistance fitness landscapes

    PubMed Central

    Baym, Michael; Kim, Seungsoo; Veres, Adrian; Bershtein, Shimon; Kishony, Roy

    2015-01-01

    Predicting evolutionary paths to antibiotic resistance is key for understanding and controlling drug resistance. When considering a single final resistant genotype, epistatic contingencies among mutations restricts evolution to a small number of adaptive paths. Less attention has been given to multi-peak landscapes, and while specific peaks can be favored, it is unknown whether and how early a commitment to final fate is made. Here we characterized a multi-peaked adaptive landscape for trimethoprim resistance by constructing all combinatorial alleles of seven resistance-conferring mutations in dihydrofolate reductase. We observe that epistatic interactions increase rather than decrease the accessibility of each peak; while they restrict the number of direct paths, they generate more indirect paths, where mutations are adaptively gained and later adaptively lost or changed. This enhanced accessibility allows evolution to proceed through many adaptive steps while delaying commitment to genotypic fate, hindering our ability to predict or control evolutionary outcomes. PMID:26060115

  9. Characterization of Antibiotic Resistance Profiles of Ocular Enterobacteriaceae Isolates.

    PubMed

    Paul-Satyaseela, Maneesh; Murali, Sowmiya; Thirunavukkarasu, Bharani; Naraharirao, Madhavan Hajib; Jambulingam, Malathi

    2016-03-01

    Emergence of extended-spectrum β-lactamase (ESBL) and fluoroquinolone resistance among ocular Enterobacteriaceae is increasing in higher frequency. Therefore, studies are being carried out to understand their multidrug resistance pattern. A total of 101 Enterobacteriaceae isolates recovered from various ocular diseases in a tertiary eye care center at Chennai, India during the period of January 2011 to June 2014 were studied. Forty one randomly chosen isolates were subjected to antibiotic susceptibility by minimum inhibitory concentration (MIC) and genotypic analysis. Of them, 16 were ESBL producers, one was carbapenemase producer and four were resistant to ertapenem which could be due to porin loss associated with AmpC production, and 17 were resistant to fluoroquinolones. Sixteen isolates harbored ESBL genes in which 14 had more than one gene and none of them were positive for blaNDM-1 gene. QNR genes were detected in 18 isolates. ESBL producers were predominantly isolated from conjunctiva. A high degree of ESBL production and fluoroquinolone resistance is seen among the genus Klebsiella sp. Hence, monitoring the rate of ESBL prevalence plays a vital role in the administration of appropriate intravitreal antibiotics to save the vision and also to reduce the development of drug resistance in ocular pathogens. PMID:27141313

  10. Characterization of Antibiotic Resistance Profiles of Ocular Enterobacteriaceae Isolates

    PubMed Central

    Paul-Satyaseela, Maneesh; Murali, Sowmiya; Thirunavukkarasu, Bharani; Naraharirao, Madhavan Hajib; Jambulingam, Malathi

    2016-01-01

    Emergence of extended-spectrum β-lactamase (ESBL) and fluoroquinolone resistance among ocular Enterobacteriaceae is increasing in higher frequency. Therefore, studies are being carried out to understand their multidrug resistance pattern. A total of 101 Enterobacteriaceae isolates recovered from various ocular diseases in a tertiary eye care center at Chennai, India during the period of January 2011 to June 2014 were studied. Forty one randomly chosen isolates were subjected to antibiotic susceptibility by minimum inhibitory concentration (MIC) and genotypic analysis. Of them, 16 were ESBL producers, one was carbapenemase producer and four were resistant to ertapenem which could be due to porin loss associated with AmpC production, and 17 were resistant to fluoroquinolones. Sixteen isolates harbored ESBL genes in which 14 had more than one gene and none of them were positive for blaNDM-1 gene. QNR genes were detected in 18 isolates. ESBL producers were predominantly isolated from conjunctiva. A high degree of ESBL production and fluoroquinolone resistance is seen among the genus Klebsiella sp. Hence, monitoring the rate of ESBL prevalence plays a vital role in the administration of appropriate intravitreal antibiotics to save the vision and also to reduce the development of drug resistance in ocular pathogens. PMID:27141313

  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

    2016-01-01

    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

  12. New and alternative approaches to tackling antibiotic resistance

    PubMed Central

    Theriault, Nicolette

    2013-01-01

    Multidrug-resistant bacteria are becoming more common and due to their multiplicity of mechanisms, they are frequently resistant to many if not all of the current antibiotics. This daunting spectre has been the target of many research efforts into conventional antibiotics and alternative approaches. This review focuses on the more recent advances in these fields with an overview on peptidomimetics, nanoparticles and their derivatives, FimH inhibitors, quorum sensing inhibition molecules, neoglycosides and phage therapies. These various approaches are at different stages of development, some are closer to the clinic than others, but recent regulatory guidance and re-awakened interest from the pharmaceutical companies gives us some optimism for the future. PMID:24381727

  13. 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

  14. 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.

  15. Antibiotic resistance: what is the impact of agricultural uses of antibiotics on children's health?

    PubMed

    Shea, Katherine M

    2003-07-01

    Antimicrobial resistance has reached crisis stage in human medicine. The rapid acceleration of multidrug-resistant bacteria in the past 2 decades has overtaken new drug development, and patients and clinicians are faced with the prospect of untreatable infections. Although much of the problem stems from overuse and misuse of antimicrobial agents in human medicine, large-scale use of antimicrobials in agriculture also contributes to the crisis. Agricultural uses of antibiotics produce environmental exposures in a variety of reservoirs, which select for resistant microbes and microbial genes. This article presents the major lines of evidence documenting the risks to human health of some of the agricultural uses of antimicrobials. A brief review of the microbiologic antecedents of resistance is followed by a discussion of agricultural uses of antimicrobials and a targeted review of the literature, which provides the background knowledge and evidence necessary for pediatricians and other clinicians to be informed and to advocate for judicious use of antimicrobials in all sectors.

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

    PubMed

    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.

  18. Meticillin-resistant Staphylococcus aureus isolated from Iranian hospitals: virulence factors and antibiotic resistance properties.

    PubMed

    Momtaz, Hassan; Hafezi, Laleh

    2014-10-05

    Staphylococcus aureus is an important opportunistic pathogen responsible for a variety of diseases. Indiscriminate prescription of antibiotics caused severe antibiotic resistance especially against commonly used drugs. The present investigation was carried out to study the distribution of Panton-Valentine Leukocidin gene, SCCmec types and antibiotic resistance properties of meticillin-resistant Staphylococcus aureus isolated from Iranian hospitals. A total of 132 clinical specimens were collected from two major Iranian hospitals. Samples were cultured and their positive results were subjected to several PCR methods. The patterns of antibiotic resistance were studied using the disk diffusion method. We found that 66 out of 132 samples (50%) were positive for Staphylococcus aureus. The most commonly infected samples were superficial and surgical wounds (66.12%). The incidence of mecA, tetK, ermA, ermC, tetM, aacA-D, linA, msrA, vatA, vatC and vatB antibiotic resistance genes were 80.30%, 34.84%, 30.30%, 25.75%, 24.24%, 19.69%, 7.57%, 7.57%, 6.06%, 3.03% and 1.51%, respectively. Totally, 40.90% of isolates harbored the Panton-Valentine Leukocidin gene. Of 53 mec positive strains, the distribution of SCCmec V, SCCmec III, SCCmec IVa, SCCmec IVc and SCCmec IVb were 28 (52.83%), 13 (24.52%), 6 (11.32%), 4 (7.54%) and 2 (3.77%), respectively. All isolates were resistant to penicillin, cephalothin, cefazoline and ceftriaxone. The high levels of Staphylococcus aureus resistance against commonly used antibiotics as well as high presence of SCCmec types of meticillin-resistant virulent strains of Staphylococcus aureus suggest that infections with these strains require more advanced hospital care with emerging demand for novel antibiotics.

  19. Enterobacter cloacae complex: clinical impact and emerging antibiotic resistance.

    PubMed

    Mezzatesta, Maria Lina; Gona, Floriana; Stefani, Stefania

    2012-07-01

    Species of the Enterobacter cloacae complex are widely encountered in nature, but they can act as pathogens. The biochemical and molecular studies on E. cloacae have shown genomic heterogeneity, comprising six species: Enterobacter cloacae, Enterobacter asburiae, Enterobacter hormaechei, Enterobacter kobei, Enterobacter ludwigii and Enterobacter nimipressuralis, E. cloacae and E. hormaechei are the most frequently isolated in human clinical specimens. Phenotypic identification of all species belonging to this taxon is usually difficult and not always reliable; therefore, molecular methods are often used. Although the E. cloacae complex strains are among the most common Enterobacter spp. causing nosocomial bloodstream infections in the last decade, little is known about their virulence-associated properties. By contrast, much has been published on the antibiotic-resistance features of these microorganisms. In fact, they are capable of overproducing AmpC β-lactamases by derepression of a chromosomal gene or by the acquisition of a transferable ampC gene on plasmids conferring the antibiotic resistance. Many other resistance determinants that are able to render ineffective almost all antibiotic families have been recently acquired. Most studies on antimicrobial susceptibility are focused on E. cloacae, E. hormaechei and E. asburiae; these studies reported small variations between the species, and the only significant differences had no discriminating features.

  20. 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.

  1. 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. PMID:18502931

  2. 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. PMID:27333280

  3. 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.

  4. Occurrence and spread of antibiotic resistances in Enterococcus faecium.

    PubMed

    Klare, Ingo; Konstabel, Carola; Badstübner, Dietlinde; Werner, Guido; Witte, Wolfgang

    2003-12-01

    Enterococci are the second to third most important bacterial genus in hospital infections. Especially Enterococcus (E.) faecium possesses a broad spectrum of natural and acquired antibiotic resistances which are presented in detail in this paper. From medical point of view, the transferable resistances to glycopeptides (e.g., vancomycin, VAN, or teicoplanin, TPL) and streptogramins (e.g., quinupristin/dalfopristin, Q/D) in enterococci are of special interest. The VanA type of enterococcal glycopeptide resistance is the most important one (VAN-r, TPL-r); its main reservoir is E. faecium. Glycopeptide-resistant E. faecium (GREF) can be found in hospitals and outside of them, namely in European commercial animal husbandry in which the glycopeptide avoparcin (AVO) was used as growth promoter in the past. There are identical types of the vanA gene clusters in enterococci from different ecological origins (faecal samples of animals, animal feed, patients in hospitals, persons in the community, waste water samples). Obviously, across the food chain (by GREF-contaminated meat products), these multiple-resistant bacteria or their vanA gene clusters can reach humans. In hospital infections, widespread epidemic-virulent E. faecium isolates of the same clone with or without glycopeptide resistance can occur; these strains often harbour different plasmids and the esp gene. This indicates that hospital-adapted epidemic-virulent E. faecium strains have picked up the vanA gene cluster after they were already widely spread. The streptogramin virginiamycin was also used as feed additive in commercial animal husbandry in Europe for more than 20 years, and it created reservoirs for streptogramin-resistant E. faecium (SREF). In 1998/1999, SREF could be isolated in Germany from waste water of sewage treatment plants, from faecal samples and meat products of animals that were fed virginiamycin (cross resistance to Q/D), from stools of humans in the community, and from clinical samples

  5. Molecular Analysis of Antibiotic Resistance Determinants and Plasmids in Malaysian Isolates of Multidrug Resistant Klebsiella pneumoniae

    PubMed Central

    Al-Marzooq, Farah; Mohd Yusof, Mohd Yasim; Tay, Sun Tee

    2015-01-01

    Infections caused by multidrug resistant Klebsiella pneumoniae have been increasingly reported in many parts of the world. A total of 93 Malaysian multidrug resistant K. pneumoniae isolated from patients attending to University of Malaya Medical Center, Kuala Lumpur, Malaysia from 2010-2012 were investigated for antibiotic resistance determinants including extended-spectrum beta-lactamases (ESBLs), aminoglycoside and trimethoprim/sulfamethoxazole resistance genes and plasmid replicons. CTX-M-15 (91.3%) was the predominant ESBL gene detected in this study. aacC2 gene (67.7%) was the most common gene detected in aminoglycoside-resistant isolates. Trimethoprim/sulfamethoxazole resistance (90.3%) was attributed to the presence of sul1 (53.8%) and dfrA (59.1%) genes in the isolates. Multiple plasmid replicons (1-4) were detected in 95.7% of the isolates. FIIK was the dominant replicon detected together with 13 other types of plasmid replicons. Conjugative plasmids (1-3 plasmids of ~3-100 kb) were obtained from 27 of 43 K. pneumoniae isolates. An ESBL gene (either CTX-M-15, CTX-M-3 or SHV-12) was detected from each transconjugant. Co-detection with at least one of other antibiotic resistance determinants [sul1, dfrA, aacC2, aac(6ˊ)-Ib, aac(6ˊ)-Ib-cr and qnrB] was noted in most conjugative plasmids. The transconjugants were resistant to multiple antibiotics including β-lactams, gentamicin and cotrimoxazole, but not ciprofloxacin. This is the first study describing the characterization of plasmids circulating in Malaysian multidrug resistant K. pneumoniae isolates. The results of this study suggest the diffusion of highly diverse plasmids with multiple antibiotic resistance determinants among the Malaysian isolates. Effective infection control measures and antibiotic stewardship programs should be adopted to limit the spread of the multidrug resistant bacteria in healthcare settings. PMID:26203651

  6. Molecular Analysis of Antibiotic Resistance Determinants and Plasmids in Malaysian Isolates of Multidrug Resistant Klebsiella pneumoniae.

    PubMed

    Al-Marzooq, Farah; Mohd Yusof, Mohd Yasim; Tay, Sun Tee

    2015-01-01

    Infections caused by multidrug resistant Klebsiella pneumoniae have been increasingly reported in many parts of the world. A total of 93 Malaysian multidrug resistant K. pneumoniae isolated from patients attending to University of Malaya Medical Center, Kuala Lumpur, Malaysia from 2010-2012 were investigated for antibiotic resistance determinants including extended-spectrum beta-lactamases (ESBLs), aminoglycoside and trimethoprim/sulfamethoxazole resistance genes and plasmid replicons. CTX-M-15 (91.3%) was the predominant ESBL gene detected in this study. aacC2 gene (67.7%) was the most common gene detected in aminoglycoside-resistant isolates. Trimethoprim/sulfamethoxazole resistance (90.3%) was attributed to the presence of sul1 (53.8%) and dfrA (59.1%) genes in the isolates. Multiple plasmid replicons (1-4) were detected in 95.7% of the isolates. FIIK was the dominant replicon detected together with 13 other types of plasmid replicons. Conjugative plasmids (1-3 plasmids of ~3-100 kb) were obtained from 27 of 43 K. pneumoniae isolates. An ESBL gene (either CTX-M-15, CTX-M-3 or SHV-12) was detected from each transconjugant. Co-detection with at least one of other antibiotic resistance determinants [sul1, dfrA, aacC2, aac(6')-Ib, aac(6')-Ib-cr and qnrB] was noted in most conjugative plasmids. The transconjugants were resistant to multiple antibiotics including β-lactams, gentamicin and cotrimoxazole, but not ciprofloxacin. This is the first study describing the characterization of plasmids circulating in Malaysian multidrug resistant K. pneumoniae isolates. The results of this study suggest the diffusion of highly diverse plasmids with multiple antibiotic resistance determinants among the Malaysian isolates. Effective infection control measures and antibiotic stewardship programs should be adopted to limit the spread of the multidrug resistant bacteria in healthcare settings.

  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 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

  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. A Survey and Analysis of the American Public's Perceptions and Knowledge About Antibiotic Resistance.

    PubMed

    Carter, Rebecca R; Sun, Jiayang; Jump, Robin L P

    2016-09-01

    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

  10. A Survey and Analysis of the American Public's Perceptions and Knowledge About Antibiotic Resistance.

    PubMed

    Carter, Rebecca R; Sun, Jiayang; Jump, Robin L P

    2016-09-01

    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.

  11. Do antibiotic residues in soils play a role in amplification and transmission of antibiotic resistant bacteria in cattle populations?

    PubMed Central

    Call, Douglas R.; Matthews, Louise; Subbiah, Murugan; Liu, Jinxin

    2013-01-01

    When we consider factors that contribute to the emergence, amplification, and persistence of antibiotic resistant bacteria, the conventional assumption is that antibiotic use is the primary driver in these processes and that selection occurs primarily in the patient or animal. Evidence suggests that this may not always be the case. Experimental trials show that parenteral administration of a third-generation cephalosporin (ceftiofur) in cattle has limited or short-term effects on the prevalence of ceftiofur-resistant bacteria in the gastrointestinal tract. While this response may be sufficient to explain a pattern of widespread resistance to cephalosporins, approximately two-thirds of ceftiofur metabolites are excreted in the urine raising the possibility that environmental selection plays an important additive role in the amplification and maintenance of antibiotic resistant E. coli on farms. Consequently, we present a rationale for an environmental selection hypothesis whereby excreted antibiotic residues such as ceftiofur are a significant contributor to the proliferation of antibiotic resistant bacteria in food animal systems. We also present a mathematical model of our hypothesized system as a guide for designing experiments to test this hypothesis. If supported for antibiotics such as ceftiofur, then there may be new approaches to combat the proliferation of antibiotic resistance beyond the prudent use mantra. PMID:23874327

  12. The lack of OmpF, but not OmpC, contributes to increased antibiotic resistance in Serratia marcescens.

    PubMed

    Moya-Torres, Aniel; Mulvey, Michael R; Kumar, Ayush; Oresnik, Ivan J; Brassinga, Ann Karen C

    2014-09-01

    The environmental organism Serratia marcescens is one of the primary causes of numerous nosocomial outbreaks and opportunistic infections. Multi-drug resistance is now a common feature among S. marcescens clinical isolates, complicating the efficacy of treatment. Recent reports have attributed antibiotic resistance to altered porin expression as well as perturbation of the intrinsic AmpC beta-lactamase production pathway. In this study, we aimed to genetically correlate the absence of OmpF and OmpC classical porins with increased antibiotic resistance. In generating isogenic porin mutant strains, we avoided incorporating additional resistance through the use of antibiotic cassettes in gene replacement and adopted an alternative strategy in creating clean unmarked mutant strains. We found that lack of OmpF, but not OmpC, significantly increased antibiotic MIC values to the beta-lactam drugs such as ampicillin and cefoxitin as well as to nitrofurantoin. Furthermore, we found that cefoxitin did not induce intrinsic AmpC beta-lactamase production, indicating that the increased MIC values were a result of reduced permeability of cefoxitin due to the lack of OmpF. Genetic deletion of both ompF and ompC did not compromise the integrity of the bacterial cell envelope in optimal growth conditions, suggesting that other outer-membrane porins may function in a compensatory role to facilitate nutrient uptake and cell envelope integrity. Taken together, to our knowledge this is the first study that genetically correlates increased antibiotic resistance with altered porin expression in S. marcescens.

  13. Antibiotic resistance and stress in the light of Fisher's model.

    PubMed

    Trindade, Sandra; Sousa, Ana; Gordo, Isabel

    2012-12-01

    The role of mutations in evolution depends upon the distribution of their effects on fitness. This distribution is likely to depend on the environment. Indeed genotype-by-environment interactions are key for the process of local adaptation and ecological specialization. An important trait in bacterial evolution is antibiotic resistance, which presents a clear case of change in the direction of selection between environments with and without antibiotics. Here, we study the distribution of fitness effects of mutations, conferring antibiotic resistance to Escherichia coli, in benign and stressful environments without drugs. We interpret the distributions in the light of a fitness landscape model that assumes a single fitness peak. We find that mutation effects (s) are well described by a shifted gamma distribution, with a shift parameter that reflects the distance to the fitness peak and varies across environments. Consistent with the theoretical predictions of Fisher's geometrical model, with a Gaussian relationship between phenotype and fitness, we find that the main effect of stress is to increase the variance in s. Our findings are in agreement with the results of a recent meta-analysis, which suggest that a simple fitness landscape model may capture the variation of mutation effects across species and environments.

  14. 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.

  15. 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.

  16. 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.

  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. 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. PMID:24619620

  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. Effect of silver nanoparticles and antibiotics on antibiotic resistance genes in anaerobic digestion.

    PubMed

    Miller, Jennifer H; Novak, John T; Knocke, William R; Young, Katherine; Hong, Yanjuan; Vikesland, Peter J; Hull, Matthew S; Pruden, Amy

    2013-05-01

    Water resource recovery facilities have been described as creating breeding ground conditions for the selection, transfer, and dissemination of antibiotic resistance genes (ARGs) among various bacteria. The objective of this study was to determine the effect of direct addition of antibiotic and silver nanoparticles (Ag NPs, or nanosilver) on the occurrence of ARGs in thermophilic anaerobic digesters. Test thermophilic digesters were amended with environmentally-relevant concentrations of Ag NP (0.01, 0.1, and 1.0 mg-Ag/L; corresponding to approximately 0.7, 7.0, and 70 mg-Ag/kg total solids) and sulfamethoxazole (SMX) that span susceptible to resistant classifications (1, 5, and 50 mg/L) as potential selection pressures for ARGs. Tetracycline (tet(O), tet(W)) and sulfonamide (sulI, sulII) ARGs and the integrase enzyme gene (intI1) associated with Class 1 integrons were measured in raw sludge, test thermophilic digesters, a control thermophilic digester, and a control mesophilic digester. There was no apparent effect of Ag NPs on thermophilic anaerobic digester performance. The maximum SMX addition (50 mg/L) resulted in accumulation of volatile fatty acids and low pH, alkalinity, and volatile solids reduction. There was no significant difference between ARG gene copy numbers (absolute or normalized to 16S rRNA genes) in amended thermophilic digesters and the control thermophilic digester. Antibiotic resistance gene copy numbers in digested sludge ranged from 10(3) to 10(6) copies per microL (approximately 8 x10(1) to 8 x 10(4) copies per microg) of sludge as result of a 1-log reduction of ARGs (2-log reduction for intI1). Quantities of the five ARGs in raw sludge ranged from 10(4) to 10(8) copies per microL (approximately 4 x 10(2) to 4 x 10(6) per microg) of sludge. Test and control thermophilic digesters (53 degrees C, 12-day solids retention time [SRT]) consistently reduced but did not eliminate levels of all analyzed genes. The mesophilic digester (37 degrees C

  2. The antibiotic resistance crisis: part 2: management strategies and new agents.

    PubMed

    Ventola, C Lee

    2015-05-01

    Controlling antibiotic-resistant bacteria calls for widespread adoption of antibiotic stewardship programs; better diagnosis, tracking and prescribing practices; optimized therapeutic regimens; prevention of infection transmission-and new drugs. PMID:25987823

  3. 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.

  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. Glycopeptide antibiotics: evolving resistance, pharmacology and adverse event profile.

    PubMed

    Henson, Karl Evans R; Levine, Miriam T; Wong, Eunice Ann H; Levine, Donald P

    2015-01-01

    The first glycopeptide antibiotic was vancomycin, isolated from the soil in the 1950s; since then, the class has expanded to include teicoplanin and the new semisynthetic glycopeptides dalbavancin, oritavancin and telavancin. They are bactericidal, active against most Gram-positive organisms, and in a concentration-dependent manner, inhibit cell wall synthesis. Resistance to vancomycin has emerged, especially among enterococci and Staphylococcus aureus through a variety of mechanisms. This emerging resistance to vancomycin makes proper dosing and monitoring of the area under the curve/MIC critically important. The chief adverse effect of vancomycin is nephrotoxicity, which is also intricately related to its dose. The efficacy of the semisynthetic glycopeptides has been demonstrated in skin and soft-tissue infections, but remains to be seen in serious methicillin-resistant Staphylococcus aureus infections.

  6. Resistance to antibiotics targeted to the bacterial cell wall

    PubMed Central

    Nikolaidis, I; Favini-Stabile, S; Dessen, A

    2014-01-01

    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. PMID:24375653

  7. Emergence of a Potent Multidrug Efflux Pump Variant That Enhances Campylobacter Resistance to Multiple Antibiotics

    PubMed Central

    Yao, Hong; Shen, Zhangqi; Wang, Yang; Deng, Fengru; Liu, Dejun; Naren, Gaowa; Dai, Lei; Su, Chih-Chia; Wang, Bing; Wang, Shaolin; Wu, Congming; Yu, Edward W.

    2016-01-01

    ABSTRACT Bacterial antibiotic efflux pumps are key players in antibiotic resistance. Although their role in conferring multidrug resistance is well documented, the emergence of “super” efflux pump variants that enhance bacterial resistance to multiple drugs has not been reported. Here, we describe the emergence of a resistance-enhancing variant (named RE-CmeABC) of the predominant efflux pump CmeABC in Campylobacter, a major zoonotic pathogen whose resistance to antibiotics is considered a serious antibiotic resistance threat in the United States. Compared to the previously characterized CmeABC transporters, RE-CmeABC is much more potent in conferring Campylobacter resistance to antibiotics, which was shown by increased MICs and reduced intracellular accumulation of antibiotics. Structural modeling suggests that sequence variations in the drug-binding pocket of CmeB possibly contribute to the enhanced efflux function. Additionally, RE-CmeABC expands the mutant selection window of ciprofloxacin, enhances the emergence of antibiotic-resistant mutants, and confers exceedingly high-level resistance to fluoroquinolones, an important class of antibiotics for clinical therapy of campylobacteriosis. Furthermore, RE-CmeABC is horizontally transferable, shifts antibiotic MIC distribution among clinical isolates, and is increasingly prevalent in Campylobacter jejuni isolates, suggesting that it confers a fitness advantage under antimicrobial selection. These findings reveal a new mechanism for enhanced multidrug resistance and an effective strategy utilized by bacteria for adaptation to selection from multiple antibiotics. PMID:27651364

  8. 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

    2016-03-01

    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.

  9. 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).

  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. PMID:27462384

  11. Abundance and dynamics of antibiotic resistance genes and integrons in lake sediment microcosms.

    PubMed

    Berglund, Björn; Khan, Ghazanfar Ali; Lindberg, Richard; Fick, Jerker; Lindgren, Per-Eric

    2014-01-01

    Antibiotic resistance in bacteria causing disease is an ever growing threat to the world. Recently, environmental bacteria have become established as important both as sources of antibiotic resistance genes and in disseminating resistance genes. Low levels of antibiotics and other pharmaceuticals are regularly released into water environments via wastewater, and the concern is that such environmental contamination may serve to create hotspots for antibiotic resistance gene selection and dissemination. In this study, microcosms were created from water and sediments gathered from a lake in Sweden only lightly affected by human activities. The microcosms were exposed to a mixture of antibiotics of varying environmentally relevant concentrations (i.e., concentrations commonly encountered in wastewaters) in order to investigate the effect of low levels of antibiotics on antibiotic resistance gene abundances and dynamics in a previously uncontaminated environment. Antibiotic concentrations were measured using liquid chromatography-tandem mass spectrometry. Abundances of seven antibiotic resistance genes and the class 1 integron integrase gene, intI1, were quantified using real-time PCR. Resistance genes sulI and ermB were quantified in the microcosm sediments with mean abundances 5 and 15 gene copies/10(6) 16S rRNA gene copies, respectively. Class 1 integrons were determined in the sediments with a mean concentration of 3.8 × 10(4) copies/106 16S rRNA gene copies. The antibiotic treatment had no observable effect on antibiotic resistance gene or integron abundances. PMID:25247418

  12. Engineered riboswitch as a gene-regulatory platform for reducing antibiotic resistance.

    PubMed

    Liu, Libing; Wang, Shu

    2014-01-01

    Antibiotic resistance (AR), the ability of a microorganism to withstand the effects of antibiotics, is a growing and increasingly serious global public health problem. Enzymatic activation of antibiotics though the production of β-lactamase is one of the main mechanisms causing AR. Synthetic riboswitch containing aptazyme is constructed in E. coli to regulate the expression of β-lactamase through small molecule-aptamer interactions, which sharply reduces the antibiotic resistance of the engineered bacteria. PMID:24549625

  13. Antibiotic Resistance in Aeromonas Upstream and Downstream of a Water Resource Recovery Facility

    PubMed Central

    Henderson, Samantha K.; Askew, Maegan L.; Risenhoover, Hollie G.; McAndrews, Chrystle R.; Kennedy, S. Dawn; Paine, C. Sue

    2014-01-01

    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 thirteen 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. PMID:25327024

  14. 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.

  15. Bypass of genetic constraints during mutator evolution to antibiotic resistance

    PubMed Central

    Couce, Alejandro; Rodríguez-Rojas, Alexandro; Blázquez, Jesús

    2015-01-01

    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. PMID:25716795

  16. Biophysical separation of Staphylococcus epidermidis strains based on antibiotic resistance.

    PubMed

    Jones, Paul V; Huey, Shannon; Davis, Paige; Yanashima, Ryan; McLemore, Ryan; McLaren, Alex; Hayes, Mark A

    2015-08-01

    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 × 10(9) V m(-2) for the resistant strain, versus 9.2 ± 0.4 × 10(9) 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

  17. Bypass of genetic constraints during mutator evolution to antibiotic resistance.

    PubMed

    Couce, Alejandro; Rodríguez-Rojas, Alexandro; Blázquez, Jesús

    2015-04-01

    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.

  18. 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

  19. CDC Vital Signs: Making Health Care Safer -- Protect Patients from Antibiotic Resistance

    MedlinePlus

    ... These six bacteria are among the most deadly antibiotic-resistant bacteria, identified as urgent or serious threats by CDC: CRE (carbapenem-resistant Enterobacteriaceae), MRSA (methicillin-resistant Staphylococcus aureus ), ESBL-producing Enterobacteriaceae (extended-spectrum ...

  20. Incidence of antibiotic-resistant Escherichia coli in milk produced in the west of Scotland.

    PubMed

    Johnston, D W; Bruce, J; Hill, J

    1983-02-01

    Antibiotic-resistant Esch. coli were found in 10.6% of milk samples collected from 998 farms in the west of Scotland. The incidence of both Esch. coli and antibiotic-resistant Esch. coli in milk was higher when the cattle were housed day and night than when they were outdoors. Of the 1125 Esch. coli isolates tested 22.2% were antibiotic resistant and of these 42.4% were resistant to more than one antibiotic. Escherichia coli carrying up to six resistance determinants were isolated. The possible implications to animal and human health are discussed.

  1. 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.

  2. 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. PMID:26613914

  3. Can chlorination co-select antibiotic-resistance genes?

    PubMed

    Lin, Wenfang; Zhang, Menglu; Zhang, Shenghua; Yu, Xin

    2016-08-01

    Selective pressures, such as chemical or heavy metal pollution, may co-select for bacterial antibiotic resistance in the environment. However, whether chlorination in water treatment can co-select antibiotic-resistant bacteria is controversial. In this study, high capacity quantitative polymerase chain reaction (qPCR) analysis was applied to target almost all known antibiotic-resistance genes (ARGs) (282 types) and 13 mobile genetic elements (MGEs) in bacteria detected in secondary effluents from a municipal wastewater treatment plant after chlorination. The results revealed that 125 unique ARGs were detected in non-chlorinated samples, and the number decreased (79-91 types) as the chlorine concentration was increased. Moreover, 7.49 × 10(4)-3.92 × 10(7) copies/100 ml water reduction of ARGs occurred with 4 mg Cl2/l. Considering the relative abundance of ARGs (i.e., ARG copies normalized to 16S rRNA gene copies), 119 ARGs decreased in response to chlorination, whereas only six ARGs, such as dfrA1, tetPB-03, tetPA, ampC-04, tetA-02, and erm(36), were potentially enriched by 10.90-, 10.06-, 8.63-, 6.86-, 3.77-, and 1.09-fold, respectively. Furthermore, the relative abundance of 12 detected MGEs was lower after chlorination. Therefore, chlorination was effective in reducing ARGs and MGEs rather than co-selecting them.

  4. Can chlorination co-select antibiotic-resistance genes?

    PubMed

    Lin, Wenfang; Zhang, Menglu; Zhang, Shenghua; Yu, Xin

    2016-08-01

    Selective pressures, such as chemical or heavy metal pollution, may co-select for bacterial antibiotic resistance in the environment. However, whether chlorination in water treatment can co-select antibiotic-resistant bacteria is controversial. In this study, high capacity quantitative polymerase chain reaction (qPCR) analysis was applied to target almost all known antibiotic-resistance genes (ARGs) (282 types) and 13 mobile genetic elements (MGEs) in bacteria detected in secondary effluents from a municipal wastewater treatment plant after chlorination. The results revealed that 125 unique ARGs were detected in non-chlorinated samples, and the number decreased (79-91 types) as the chlorine concentration was increased. Moreover, 7.49 × 10(4)-3.92 × 10(7) copies/100 ml water reduction of ARGs occurred with 4 mg Cl2/l. Considering the relative abundance of ARGs (i.e., ARG copies normalized to 16S rRNA gene copies), 119 ARGs decreased in response to chlorination, whereas only six ARGs, such as dfrA1, tetPB-03, tetPA, ampC-04, tetA-02, and erm(36), were potentially enriched by 10.90-, 10.06-, 8.63-, 6.86-, 3.77-, and 1.09-fold, respectively. Furthermore, the relative abundance of 12 detected MGEs was lower after chlorination. Therefore, chlorination was effective in reducing ARGs and MGEs rather than co-selecting them. PMID:27192478

  5. 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 ...

  6. Antibiotic resistance of bacteria in raw and biologically treated sewage and in groundwater below leaking sewers.

    PubMed

    Gallert, C; Fund, K; Winter, J

    2005-11-01

    More than 750 isolates of faecal coliforms (>200 strains), enterococci (>200 strains) and pseudomonads (>340 strains) from three wastewater treatment plants (WTPs) and from four groundwater wells in the vicinity of leaking sewers were tested for resistance against 14 antibiotics. Most, or at least some, strains of the three bacterial groups, isolated from raw or treated sewage of the three WTPs, were resistant against penicillin G, ampicillin, vancomycin, erythromycin, triple sulfa and trimethoprim/sulfamethoxazole (SXT). Only a few strains of pseudomonads or faecal coliforms were resistant against some of the other tested antibiotics. The antibiotic resistances of pseudomonads, faecal coliforms and enterococci from groundwater varied to a higher extent. In contrast to the faecal coliforms and enterococci, most pseudomonads from all groundwater samples, including those from non-polluted groundwater, were additionally resistant against chloramphenicol and SXT. Pseudomonads from sewage and groundwater had more multiple antibiotic resistances than the faecal coliforms or the enterococci, and many pseudomonads from groundwater were resistant to more antibiotics than those from sewage. The pseudomonads from non-polluted groundwater were the most resistant isolates of all. The few surviving faecal coliforms in groundwater seemed to gain multiple antibiotic resistances, whereas the enterococci lost antibiotic resistances. Pseudomonads, and presumably, other autochthonous soil or groundwater bacteria, such as antibiotic-producing Actinomyces sp., seem to contribute significantly to the gene pool for acquisition of resistances against antibiotics in these environments. PMID:16001254

  7. 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. PMID:27065408

  8. 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.

  9. Bacterial antibiotic resistance: frequency of gentamicin-resistant strains of Escherichia coli in the fecal microflora of commercial turkeys.

    PubMed

    Dubel, J R; Zink, D L; Kelley, L M; Naqi, S A; Renshaw, H W

    1982-10-01

    The relationship of subtherapeutic feeding and parenteral injection of antibiotics to the presence of antibiotic resistant strains of Escherichia coli in the fecal microflora of commercial turkeys has been investigated. Cloacal swabs collected from 137 commercial turkeys were examined for E coli resistant to gentamicin. Gentamicin-resistant E coli organisms were isolated and tested for resistance to ampicillin, chloramphenicol, kanamycin, streptomycin, and tetracycline. Strains of E coli resistant to gentamicin were identified in 118 of 137 (86.1%) specimens evaluated. There were 5 different antibiotic resistance patterns exhibited by the gentamicin-resistant strains of E coli. All strains showed a common antibiotic resistance pattern of gentamicin, kanamycin, and streptomycin. The results of the antibiotic susceptibility tests were compared to the known history of antibiotic usage in each flock. There was no significant correlation between the use of subtherapeutic concentrations of antibiotics and the frequency of gentamicin resistant E coli. However, the frequency of gentamicin-resistant E coli was closely related to the age of the bird, with birds less than 12 weeks of age being most likely to harbor E coli resistant to gentamicin. This age-dependent frequency of gentamicin-resistant E coli was associated with the common practice of dipping eggs in gentamicin and injecting newly hatched poults with gentamicin, but not with the feeding of subtherapeutic concentrations of antibiotics.

  10. Magnetic isotope effect of magnesium (25)Mg on E. coli resistance to antibiotics.

    PubMed

    Letuta, U G; Vekker, A S; Kornilova, T A; Gryaznov, A A; Cheplakov, I A

    2016-07-01

    Effects of synergism and antagonism of antibacterial drugs and magnetic isotope of magnesium (25)Mg on antibiotic resistance of bacteria E. coli were discovered. Fourteen antibiotics from seven different groups were tested. The increase in antibiotic resistance in the presence of the ion (25)Mg(2+) was discovered in E. coli cells incubated with quinolones/fluoroquinolones, indicating the inhibiting effect of the magnetic moments of nuclei (25)Mg on DNA synthesis. The change in antibiotic resistance was also detected in bacteria affected by magnesium (25)Mg and certain antibiotics from aminoglycoside and lincosamide groups. PMID:27599512

  11. Potential ecological and human health impacts of antibiotics and antibiotic-resistant bacteria from wastewater treatment plants.

    PubMed

    Kim, Sungpyo; Aga, Diana S

    2007-12-01

    The occurrence of antibiotics and other pharmaceuticals in the environment has become an increasing public concern as recent environmental monitoring activities reveal the presence of a broad range of persistent pharmaceuticals in soil and water. Studies show that municipal wastewater treatment plants (WWTPs) are important point sources of antibiotics and antibiotic-resistant bacteria in the environment. The fate of antibiotics and other pharmaceuticals in WWTPs is greatly influenced by the design and operation of treatment systems. Because knowledge on the fate of antibiotics and resistant bacteria in WWTPs is important in estimating their potential impacts on ecology and human health, investigations on occurrence, treatment, and observed effects are reviewed in this article. In addition, human health risk assessment protocols for antibiotic and resistant bacteria are described. Although data on other pharmaceutical compounds are also presented, discussion is focused on antibiotics in the environment because of the potential link to increased emergence of resistance among pathogenic bacteria. The applications of modern analytical methods that facilitate the identification of novel transformation products of pharmaceuticals in environmental matrices are also included to illustrate that the disappearance of the parent pharmaceuticals in WWTPs does not necessarily equate to their complete removal.

  12. 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.

  13. 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. PMID:26976842

  14. 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

  15. How Should We Be Determining Background and Baseline Antibiotic Resistance Levels in Agroecosystem Research?

    PubMed

    Rothrock, Michael J; Keen, Patricia L; Cook, Kimberly L; Durso, Lisa M; Franklin, Alison M; Dungan, Robert S

    2016-03-01

    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 understand the potential risks to human, animal, and ecological health in systems altered by antibiotic-resistance-related contamination. At present, analyzing and interpreting the effects of human and animal inputs on antibiotic resistance in agroecosystems is difficult, since standard research terminology and protocols do not exist for studying background and baseline levels of resistance in the environment. To improve the state of science in antibiotic-resistance-related research in agroecosystems, researchers are encouraged to incorporate baseline data within the study system and background data from outside the study system to normalize the study data and determine the potential impact of antibiotic-resistance-related determinants on a specific agroecosystem. Therefore, the aims of this review were to (i) present standard definitions for commonly used terms in environmental antibiotic resistance research and (ii) illustrate the need for research standards (normalization) within and between studies of antibiotic resistance in agroecosystems. To foster synergy among antibiotic resistance researchers, a new surveillance and decision-making tool is proposed to assist researchers in determining the most relevant and important antibiotic-resistance-related targets to focus on in their given agroecosystems. Incorporation of these components within antibiotic-resistance-related studies should allow for a more comprehensive and accurate picture of the current and future states of antibiotic resistance in the environment. PMID:27065388

  16. How Should We Be Determining Background and Baseline Antibiotic Resistance Levels in Agroecosystem Research?

    PubMed

    Rothrock, Michael J; Keen, Patricia L; Cook, Kimberly L; Durso, Lisa M; Franklin, Alison M; Dungan, Robert S

    2016-03-01

    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 understand the potential risks to human, animal, and ecological health in systems altered by antibiotic-resistance-related contamination. At present, analyzing and interpreting the effects of human and animal inputs on antibiotic resistance in agroecosystems is difficult, since standard research terminology and protocols do not exist for studying background and baseline levels of resistance in the environment. To improve the state of science in antibiotic-resistance-related research in agroecosystems, researchers are encouraged to incorporate baseline data within the study system and background data from outside the study system to normalize the study data and determine the potential impact of antibiotic-resistance-related determinants on a specific agroecosystem. Therefore, the aims of this review were to (i) present standard definitions for commonly used terms in environmental antibiotic resistance research and (ii) illustrate the need for research standards (normalization) within and between studies of antibiotic resistance in agroecosystems. To foster synergy among antibiotic resistance researchers, a new surveillance and decision-making tool is proposed to assist researchers in determining the most relevant and important antibiotic-resistance-related targets to focus on in their given agroecosystems. Incorporation of these components within antibiotic-resistance-related studies should allow for a more comprehensive and accurate picture of the current and future states of antibiotic resistance in the environment.

  17. Applying the emergency risk management process to tackle the crisis of antibiotic resistance.

    PubMed

    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

  18. 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.

  19. 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

  20. Resident microbiota of the gypsy moth midgut harbors antibiotic resistance determinants.

    PubMed

    Allen, Heather K; Cloud-Hansen, Karen A; Wolinski, Joseph M; Guan, Changhui; Greene, Serena; Lu, Shyue; Boeyink, Mallory; Broderick, Nichole A; Raffa, Kenneth F; Handelsman, Jo

    2009-03-01

    Little is known about the significance of insects as environmental reservoirs of antibiotic-resistant bacteria. We characterized the antibiotic resistome of the microbial community in gypsy moth larval midguts by applying functional metagenomics to cultured isolates. The minimum inhibitory concentrations of 12 antibiotics were determined for 44 cultured isolates, and antibiotic resistance genes were selected from metagenomic libraries derived from DNA extracted from a pool of the isolates. Six unique clones were identified. Two were highly resistant to penicillin-type beta-lactams, two were moderately resistant to erythromycin, and two were moderately resistant to a range of antibiotics, including erythromycin, carbenicillin, and chloramphenicol. Sequence analysis predicted that the active genes encoded efflux pumps, a transcriptional activator of efflux pump protein expression, and an extended-spectrum class A beta-lactamase. Insect guts are a reservoir of antibiotic resistance genes with the potential for dissemination.

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Antibiotic resistant Staphylococcus aureus: a paradigm of adaptive power

    PubMed Central

    de Lencastre, Herminia; Oliveira, Duarte; Tomasz, Alexander

    2009-01-01

    Summary Nothing documents better the spectacular adaptive capacity of Staphylococcus aureus than the response of this important human and animal pathogen to the introduction of antimicrobial agents into the clinical environment. The effectiveness of penicillin introduced in the early 1940s was virtually annulled within a decade due to the plasmid epidemics that spread the ß-lactamase gene through the entire species of S. aureus. In 1960 within one to two years of the introduction of penicillinase resistant ß-lactams (methicillin), methicillin resistant S. aureus (MRSA) strains were identified in clinical specimens. By the 1980s, epidemic clones of MRSA acquired multidrug resistant traits and spread worldwide to become one of the most important causative agents of hospital acquired infections. In the early 2000s, MRSA strains carrying the Tn1546 transposon-based enterococcal vancomycin resistant mechanism were identified in clinical specimens, bringing the specter of a totally resistant bacterial pathogen closer to reality. Then, in the late 1990s, just as effective hygienic and antibiotic use policies managed to bring down the frequency of MRSA in hospitals of several countries, MRSA strains began to show up in the community. PMID:17921044

  7. Exploring antibiotic resistance genes and metal resistance genes in plasmid metagenomes from wastewater treatment plants.

    PubMed

    Li, An-Dong; Li, Li-Guan; Zhang, Tong

    2015-01-01

    Plasmids operate as independent genetic elements in microorganism communities. Through horizontal gene transfer (HGT), they can provide their host microorganisms with important functions such as antibiotic resistance and heavy metal resistance. In this study, six metagenomic libraries were constructed with plasmid DNA extracted from influent, activated sludge (AS) and digested sludge (DS) of two wastewater treatment plants (WWTPs). Compared with the metagenomes of the total DNA extracted from the same sectors of the wastewater treatment plant, the plasmid metagenomes had significantly higher annotation rates, indicating that the functional genes on plasmids are commonly shared by those studied microorganisms. Meanwhile, the plasmid metagenomes also encoded many more genes related to defense mechanisms, including ARGs. Searching against an antibiotic resistance genes (ARGs) database and a metal resistance genes (MRGs) database revealed a broad-spectrum of antibiotic (323 out of a total 618 subtypes) and MRGs (23 out of a total 23 types) on these plasmid metagenomes. The influent plasmid metagenomes contained many more resistance genes (both ARGs and MRGs) than the AS and the DS metagenomes. Sixteen novel plasmids with a complete circular structure that carried these resistance genes were assembled from the plasmid metagenomes. The results of this study demonstrated that the plasmids in WWTPs could be important reservoirs for resistance genes, and may play a significant role in the horizontal transfer of these genes. PMID:26441947

  8. Exploring antibiotic resistance genes and metal resistance genes in plasmid metagenomes from wastewater treatment plants

    PubMed Central

    Li, An-Dong; Li, Li-Guan; Zhang, Tong

    2015-01-01

    Plasmids operate as independent genetic elements in microorganism communities. Through horizontal gene transfer (HGT), they can provide their host microorganisms with important functions such as antibiotic resistance and heavy metal resistance. In this study, six metagenomic libraries were constructed with plasmid DNA extracted from influent, activated sludge (AS) and digested sludge (DS) of two wastewater treatment plants (WWTPs). Compared with the metagenomes of the total DNA extracted from the same sectors of the wastewater treatment plant, the plasmid metagenomes had significantly higher annotation rates, indicating that the functional genes on plasmids are commonly shared by those studied microorganisms. Meanwhile, the plasmid metagenomes also encoded many more genes related to defense mechanisms, including ARGs. Searching against an antibiotic resistance genes (ARGs) database and a metal resistance genes (MRGs) database revealed a broad-spectrum of antibiotic (323 out of a total 618 subtypes) and MRGs (23 out of a total 23 types) on these plasmid metagenomes. The influent plasmid metagenomes contained many more resistance genes (both ARGs and MRGs) than the AS and the DS metagenomes. Sixteen novel plasmids with a complete circular structure that carried these resistance genes were assembled from the plasmid metagenomes. The results of this study demonstrated that the plasmids in WWTPs could be important reservoirs for resistance genes, and may play a significant role in the horizontal transfer of these genes. PMID:26441947

  9. 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

  10. Rapid identification of antibiotic resistance using droplet microfluidics.

    PubMed

    Keays, Marie C; O'Brien, Mark; Hussain, Anam; Kiely, Patrick A; Dalton, Tara

    2016-04-01

    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.

  11. Tragedy of the commons among antibiotic resistance plasmids.

    PubMed

    Smith, Jeff

    2012-04-01

    As social interactions are increasingly recognized as important determinants of microbial fitness, sociobiology is being enlisted to better understand the evolution of clinically relevant microbes and, potentially, to influence their evolution to aid human health. Of special interest are situations in which there exists a "tragedy of the commons," where natural selection leads to a net reduction in fitness for all members of a population. Here, I demonstrate the existence of a tragedy of the commons among antibiotic resistance plasmids of bacteria. In serial transfer culture, plasmids evolved a greater ability to superinfect already-infected bacteria, increasing plasmid fitness when evolved genotypes were rare. Evolved plasmids, however, fell victim to their own success, reducing the density of their bacterial hosts when they became common and suffering reduced fitness through vertical transmission. Social interactions can thus be an important determinant of evolution for the molecular endosymbionts of bacteria. These results also identify an avenue of evolution that reduces proliferation of both antibiotic resistance genes and their bacterial hosts. PMID:22486703

  12. Tragedy of the commons among antibiotic resistance plasmids.

    PubMed

    Smith, Jeff

    2012-04-01

    As social interactions are increasingly recognized as important determinants of microbial fitness, sociobiology is being enlisted to better understand the evolution of clinically relevant microbes and, potentially, to influence their evolution to aid human health. Of special interest are situations in which there exists a "tragedy of the commons," where natural selection leads to a net reduction in fitness for all members of a population. Here, I demonstrate the existence of a tragedy of the commons among antibiotic resistance plasmids of bacteria. In serial transfer culture, plasmids evolved a greater ability to superinfect already-infected bacteria, increasing plasmid fitness when evolved genotypes were rare. Evolved plasmids, however, fell victim to their own success, reducing the density of their bacterial hosts when they became common and suffering reduced fitness through vertical transmission. Social interactions can thus be an important determinant of evolution for the molecular endosymbionts of bacteria. These results also identify an avenue of evolution that reduces proliferation of both antibiotic resistance genes and their bacterial hosts.

  13. 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

  14. 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.

  15. Clusters of antibiotic resistance genes enriched together stay together in swine agriculture

    DOE PAGES

    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 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

  16. Educational interventions to improve antibiotic use in the community: report from the International Forum on Antibiotic Resistance (IFAR) colloquium, 2002.

    PubMed

    Finch, Roger G; Metlay, Joshua P; Davey, Peter G; Baker, Lee J

    2004-01-01

    National and international strategies for the control of antibiotic resistance recommend education for health-care professionals and the public to promote prudent antibiotic use. This paper, based on discussions at the 2002 colloquium of the International Forum on Antibiotic Resistance (IFAR), provides an international discourse between theoretical approaches to behaviour change and practical experience gained in large-scale antibiotic use educational campaigns. Interventions are more likely to be effective if their aim is to change behaviour, rather than provide information. They should target all relevant groups, especially parents, children, day-care staff, and health-care professionals. They should use clear and consistent messages concerning bacterial versus viral infection, prudent antibiotic use, symptomatic treatment, and infection-control measures (eg, handwashing). Campaigns should use a range of communications using pilot-testing, strong branding, and sociocultural adaptation. Prime-time television is likely to be the most effective public medium, while academic detailing is especially useful for health-care professionals. Multifaceted interventions can improve antibiotic prescribing to some degree. However, there are few data on their effects on resistance patterns and patient outcomes, and on their cost-effectiveness. Current research aims include the application of behaviour-change models, the development and validation of prudent antibiotic prescribing standards, and the refinement of tools to assess educational interventions. PMID:14720568

  17. 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

  18. Temporal Variabilities in Genetic Patterns and Antibiotic Resistance Profiles of Enterococci Isolated from Human Feces.

    PubMed

    Nishiyama, Masateru; Shimauchi, Hidetaka; Suzuki, Yoshihiro

    2016-06-25

    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.

  19. 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

  20. 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

  1. 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 ...

  2. 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.

  3. [The roles of epigenetics and protein post-translational modifications in bacterial antibiotic resistance].

    PubMed

    Xie, Longxiang; Yu, Zhaoxiao; Guo, Siyao; Li, Ping; Abdalla, Abualgasim Elgaili; Xie, Jianping

    2015-08-01

    The increasing antibiotic resistance is now threatening to take us back to a pre-antibiotic era. Bacteria have evolved diverse resistance mechanisms, on which in-depth research could help the development of new strategies to control antibiotic-resistant infections. Epigenetic alterations and protein post-translational modifications (PTMs) play important roles in multiple cellular processes such as metabolism, signal transduction, protein degradation, DNA replication regulation and stress response. Recent studies demonstrated that epigenetics and PTMs also play vital roles in bacterial antibiotic resistance. In this review, we summarize the regulatory roles of epigenetic factors including DNA methylation and regulatory RNAs as well as PTMs such as phosphorylation and succinylation in bacterial antibiotic resistance, which may provide innovative perspectives on selecting antibacterial targets and developing antibiotics. PMID:26266782

  4. Antibiotic resistance and virulence: Understanding the link and its consequences for prophylaxis and therapy.

    PubMed

    Guillard, Thomas; Pons, Stéphanie; Roux, Damien; Pier, Gerald B; Skurnik, David

    2016-07-01

    "Antibiotic resistance is usually associated with a fitness cost" is frequently accepted as common knowledge in the field of infectious diseases. However, with the advances in high-throughput DNA sequencing that allows for a comprehensive analysis of bacterial pathogenesis at the genome scale, including antibiotic resistance genes, it appears that this paradigm might not be as solid as previously thought. Recent studies indicate that antibiotic resistance is able to enhance bacterial fitness in vivo with a concomitant increase in virulence during infections. As a consequence, strategies to minimize antibiotic resistance turn out to be not as simple as initially believed. Indeed, decreased antibiotic use may not be sufficient to let susceptible strains outcompete the resistant ones. Here, we put in perspective these findings and review alternative approaches, such as preventive and therapeutic anti-bacterial immunotherapies that have the potential to by-pass the classic antibiotics.

  5. 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...

  6. Monitoring of antibiotic resistance rates of Helicobacter pylori in Austrian children, 2002-2009.

    PubMed

    Prechtl, Johannes; Deutschmann, Andrea; Savic, Tamara; Jahnel, Jörg; Bogiatzis, Athanasios; Muntean, Wolfgang; Hauer, Almuthe C; Hoffmann, Karl Martin

    2012-03-01

    We retrospectively studied antibiotic resistance rates of H. pylori and their temporal changes in children. Resistance rates were 21.6% for both clarithromycin and metronidazole. There was no overall difference between children with or without migrational background. Resistance rates increased over time, and patients without migrational background showed a significant increase in metronidazole resistance. Our study emphasizes antibiotic resistance monitoring of H. pylori in children.

  7. Autoimmune mechanisms in antibiotic treatment-resistant lyme arthritis.

    PubMed

    Steere, A C; Gross, D; Meyer, A L; Huber, B T

    2001-05-01

    In about 10% of patients with Lyme arthritis in the United States, joint inflammation persists for months or even several years after the apparent eradication of the spirochete, Borrelia burgdorferi, from the joint with antibiotic treatment. We propose a model of molecular mimicry affecting genetically susceptible individuals to explain this treatment-resistant course. The majority of patients with treatment-resistant Lyme arthritis have HLA-DRB1*0401 or related alleles, and the severity and duration of their arthritis correlate with cellular and humoral immune responses to outer-surface protein A OspA) of the spirochete. Using an algorithm, the immunodominant epitope of OspA presented by the DRB1*0401 molecule was predicted to be located at aa 165-173. In a search of the Genetics Computer Group gene bank, only one human protein was identified, lymphocyte function associated antigen-1 (hLFA-1), that had sequence homology with OspA(165-173)and predicted binding in the DRB1*0401 molecule. Synovial fluid T cells from most patients with treatment-resistant arthritis responded to both OspA and hLFA-1, whereas those from patients with other forms of chronic inflammatory arthritis did not. Molecular mimicry between a dominant T cell epitope of OspA and hLFA-1 may be an important factor in the persistence of joint inflammation in genetically susceptible patients with treatment-resistant Lyme arthritis.

  8. 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.

  9. 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.

  10. 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. PMID:27194288

  11. Effects of antibiotic resistance alleles on bacterial evolutionary responses to viral parasites

    PubMed Central

    Hall, Alex R.

    2016-01-01

    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. PMID:27194288

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. Prevalence and characterization of antibiotic resistant Enterococcus faecalis in French cheeses.

    PubMed

    Jamet, Emmanuel; Akary, Elodie; Poisson, Marie-Ange; Chamba, Jean-François; Bertrand, Xavier; Serror, Pascale

    2012-09-01

    Prevalence of enterococci and antibiotic resistance profiles of Enterococcus faecalis was analyzed in 126 French cheeses from retail stores. Forty-four percent of pasteurized or thermised-milk cheeses, and up to 92% of raw-milk cheeses contained detectable enterococci. A total of 337 antibiotic resistant enterococci were isolated in 29% and 60% of pasteurized-milk and raw-milk cheeses, respectively. E. faecalis was the predominant antibiotic resistant species recovered (81%), followed by Enterococcus faecium (13%), and Enterococcus durans (6%). The most prevalent antibiotic resistances were tetracycline (Tet) and minocycline (Min), followed by erythromycin (Ery), kanamycin (Kan) and chloramphenicol (Cm). The most common multiple antibiotic resistance phenotype was Cm Ery Kan Min Tet. The occurrence of antibiotic genes, as searched by PCR, was 100 % for aph3'IIIa, 96 % for ermB, 90 % for tetM and 80 % for catA in isolates resistant to Kan, Ery, Tet or Cm, respectively. MLST analysis of 30 multidrug resistant E. faecalis revealed that ST19, CC21, CC25 and CC55 isolates were the most common in cheeses. In conclusion, as in many other European countries, French cheeses do contain enterococci with multiple antibiotics resistances. However, low occurrence of high-level gentamicin resistant or sulfamethoxazole/trimethoprim-resistant enterococci and absence of vancomycin- or ampicillin- resistant enterococci indicate that cheeses cannot be considered as a major reservoir for nosocomial multi-drug resistant enterococci.

  19. Occurrence of antibiotics and antibiotic resistance genes in hospital and urban wastewaters and their impact on the receiving river.

    PubMed

    Rodriguez-Mozaz, Sara; Chamorro, Sara; Marti, Elisabet; Huerta, Belinda; Gros, Meritxell; Sànchez-Melsió, Alexandre; Borrego, Carles M; Barceló, Damià; Balcázar, Jose Luis

    2015-02-01

    Antibiotic resistance has become a major health concern; thus, there is a growing interest in exploring the occurrence of antibiotic resistance genes (ARGs) in the environment as well as the factors that contribute to their emergence. Aquatic ecosystems provide an ideal setting for the acquisition and spread of ARGs due to the continuous pollution by antimicrobial compounds derived from anthropogenic activities. We investigated, therefore, the pollution level of a broad range of antibiotics and ARGs released from hospital and urban wastewaters, their removal through a wastewater treatment plant (WWTP) and their presence in the receiving river. Several antimicrobial compounds were detected in all water samples collected. Among antibiotic families, fluoroquinolones were detected at the highest concentration, especially in hospital effluent samples. Although good removal efficiency by treatment processes was observed for several antimicrobial compounds, most antibiotics were still present in WWTP effluents. The results also revealed that copy numbers of ARGs, such as blaTEM (resistance to β-lactams), qnrS (reduced susceptibility to fluoroquinolones), ermB (resistance to macrolides), sulI (resistance to sulfonamides) and tetW (resistance to tetracyclines), were detected at the highest concentrations in hospital effluent and WWTP influent samples. Although there was a significant reduction in copy numbers of these ARGs in WWTP effluent samples, this reduction was not uniform across analyzed ARGs. Relative concentration of ermB and tetW genes decreased as a result of wastewater treatment, whereas increased in the case of blaTEM, sulI and qnrS genes. The incomplete removal of antibiotics and ARGs in WWTP severely affected the receiving river, where both types of emerging pollutants were found at higher concentration in downstream waters than in samples collected upstream from the discharge point. Taken together, our findings demonstrate a widespread occurrence of

  20. Long-Term Shifts in Patterns of Antibiotic Resistance in Enteric Bacteria

    PubMed Central

    Houndt, Tara; Ochman, Howard

    2000-01-01

    Several mechanisms are responsible for the ability of microorganisms to tolerate antibiotics, and the incidence of resistance to these compounds within bacterial species has increased since the commercial use of antibiotics became widespread. To establish the extent of and changes in the diversity of antibiotic resistance patterns in natural populations, we determined the MICs of five antibiotics for collections of enteric bacteria isolated from diverse hosts and geographic locations and during periods before and after commercial application of antibiotics began. All of the pre-antibiotic era strains were susceptible to high levels of these antibiotics, whereas 20% of strains from contemporary populations of Escherichia coli and Salmonella enterica displayed high-level resistance to at least one of the antibiotics. In addition to the increase in the frequency of high-level resistance, background levels, conferred by genes providing nonspecific low-level resistance to multiple antibiotics, were significantly higher among contemporary strains. Changes in the incidence and levels of antibiotic resistance are not confined to particular segments of the bacterial population and reflect responses to the increased exposure of bacteria to antimicrobial compounds over the past several decades. PMID:11097921

  1. 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