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Jo Handelsman - One of the best experts on this subject based on the ideXlab platform.
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diverse Antibiotic Resistance genes in dairy cow manure
Mbio, 2014Co-Authors: Fabienne Wichmann, Nikolina Udikovickolic, S M Andrew, Jo HandelsmanAbstract:ABSTRACT Application of manure from Antibiotic-treated animals to crops facilitates the dissemination of Antibiotic Resistance determinants into the environment. However, our knowledge of the identity, diversity, and patterns of distribution of these Antibiotic Resistance determinants remains limited. We used a new combination of methods to examine the resistome of dairy cow manure, a common soil amendment. Metagenomic libraries constructed with DNA extracted from manure were screened for Resistance to beta-lactams, phenicols, aminoglycosides, and tetracyclines. Functional screening of fosmid and small-insert libraries identified 80 different Antibiotic Resistance genes whose deduced protein sequences were on average 50 to 60% identical to sequences deposited in GenBank. The Resistance genes were frequently found in clusters and originated from a taxonomically diverse set of species, suggesting that some microorganisms in manure harbor multiple Resistance genes. Furthermore, amid the great genetic diversity in manure, we discovered a novel clade of chloramphenicol acetyltransferases. Our study combined functional metagenomics with third-generation PacBio sequencing to significantly extend the roster of functional Antibiotic Resistance genes found in animal gut bacteria, providing a particularly broad resource for understanding the origins and dispersal of Antibiotic Resistance genes in agriculture and clinical settings. IMPORTANCE The increasing prevalence of Antibiotic Resistance among bacteria is one of the most intractable challenges in 21st-century public health. The origins of Resistance are complex, and a better understanding of the impacts of Antibiotics used on farms would produce a more robust platform for public policy. Microbiomes of farm animals are reservoirs of Antibiotic Resistance genes, which may affect distribution of Antibiotic Resistance genes in human pathogens. Previous studies have focused on Antibiotic Resistance genes in manures of animals subjected to intensive Antibiotic use, such as pigs and chickens. Cow manure has received less attention, although it is commonly used in crop production. Here, we report the discovery of novel and diverse Antibiotic Resistance genes in the cow microbiome, demonstrating that it is a significant reservoir of Antibiotic Resistance genes. The genomic resource presented here lays the groundwork for understanding the dispersal of Antibiotic Resistance from the agroecosystem to other settings.
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Call of the wild: Antibiotic Resistance genes in natural environments
Nature Reviews Microbiology, 2010Co-Authors: Heather K Allen, Justin Donato, Helena Huimi Wang, Karen A. Cloud-hansen, Julian Davies, Jo HandelsmanAbstract:Antibiotic-resistant pathogens are profoundly important to human health, but the environmental reservoirs of Resistance determinants are poorly understood. The origins of Antibiotic Resistance in the environment is relevant to human health because of the increasing importance of zoonotic diseases as well as the need for predicting emerging resistant pathogens. This Review explores the presence and spread of Antibiotic Resistance in non-agricultural, non-clinical environments and demonstrates the need for more intensive investigation on this subject.
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uncultured soil bacteria are a reservoir of new Antibiotic Resistance genes
Environmental Microbiology, 2004Co-Authors: Christian S Riesenfeld, Robert M Goodman, Jo HandelsmanAbstract:Antibiotic Resistance genes are typically isolated by cloning from cultured bacteria or by polymerase chain reaction (PCR) amplification from environmental samples. These methods do not access the potential reservoir of undiscovered Antibiotic Resistance genes harboured by soil bacteria because most soil bacteria are not cultured readily, and PCR detection of Antibiotic Resistance genes depends on primers that are based on known genes. To explore this reservoir, we isolated DNA directly from soil samples, cloned the DNA and selected for clones that expressed Antibiotic Resistance in Escherichia coli. We constructed four libraries that collectively contain 4.1 gigabases of cloned soil DNA. From these and two previously reported libraries, we identified nine clones expressing Resistance to aminoglycoside Antibiotics and one expressing tetracycline Resistance. Based on the predicted amino acid sequences of the Resistance genes, the Resistance mechanisms include efflux of tetracycline and inactivation of aminoglycoside Antibiotics by phosphorylation and acetylation. With one exception, all the sequences are considerably different from previously reported sequences. The results indicate that soil bacteria are a reservoir of Antibiotic Resistance genes with greater genetic diversity than previously accounted for, and that the diversity can be surveyed by a culture-independent method.
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uncultured soil bacteria are a reservoir of new Antibiotic Resistance genes
Environmental Microbiology, 2004Co-Authors: Christian S Riesenfeld, Robert M Goodman, Jo HandelsmanAbstract:Antibiotic Resistance genes are typically isolated by cloning from cultured bacteria or by polymerase chain reaction (PCR) amplification from environmental samples. These methods do not access the potential reservoir of undiscovered Antibiotic Resistance genes harboured by soil bacteria because most soil bacteria are not cultured readily, and PCR detection of Antibiotic Resistance genes depends on primers that are based on known genes. To explore this reservoir, we isolated DNA directly from soil samples, cloned the DNA and selected for clones that expressed Antibiotic Resistance in Escherichia coli. We constructed four libraries that collectively contain 4.1 gigabases of cloned soil DNA. From these and two previously reported libraries, we identified nine clones expressing Resistance to aminoglycoside Antibiotics and one expressing tetracycline Resistance. Based on the predicted amino acid sequences of the Resistance genes, the Resistance mechanisms include efflux of tetracycline and inactivation of aminoglycoside Antibiotics by phosphorylation and acetylation. With one exception, all the sequences are considerably different from previously reported sequences. The results indicate that soil bacteria are a reservoir of Antibiotic Resistance genes with greater genetic diversity than previously accounted for, and that the diversity can be surveyed by a culture-independent method.
Jose L Martinez - One of the best experts on this subject based on the ideXlab platform.
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Antibiotic Resistance evolution is contingent on the quorum sensing response in pseudomonas aeruginosa
Molecular Biology and Evolution, 2019Co-Authors: Sara Hernandoamado, Fernando Sanzgarcia, Jose L MartinezAbstract:Different works have explored independently the evolution toward Antibiotic Resistance and the role of eco-adaptive mutations in the adaptation to a new habitat (as the infected host) of bacterial pathogens. However, knowledge about the connection between both processes is still limited. We address this issue by comparing the evolutionary trajectories toward Antibiotic Resistance of a Pseudomonas aeruginosa lasR defective mutant and its parental wild-type strain, when growing in presence of two ribosome-targeting Antibiotics. Quorum-sensing lasR defective mutants are selected in P. aeruginosa populations causing chronic infections. Further, we observed they are also selected in vitro as a first adaptation for growing in culture medium. By using experimental evolution and whole-genome sequencing, we found that the evolutionary trajectories of P. aeruginosa in presence of these Antibiotics are different in lasR defective and in wild-type backgrounds, both at the phenotypic and the genotypic levels. Recreation of a set of mutants in both genomic backgrounds (either wild type or lasR defective) allowed us to determine the existence of negative epistatic interactions between lasR and Antibiotic Resistance determinants. These epistatic interactions could lead to mutual contingency in the evolution of Antibiotic Resistance when P. aeruginosa colonizes a new habitat in presence of Antibiotics. If lasR mutants are selected first, this would constraint Antibiotic Resistance evolution. Conversely, when Resistance mutations (at least those studied in the present work) are selected, lasR mutants may not be selected in presence of Antibiotics. These results underlie the importance of contingency and epistatic interactions in modulating Antibiotic Resistance evolution.
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emergence and spread of Antibiotic Resistance setting a parameter space
Upsala Journal of Medical Sciences, 2014Co-Authors: Jose L Martinez, Fernando BaqueroAbstract: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.
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natural Antibiotic Resistance and contamination by Antibiotic Resistance determinants the two ages in the evolution of Resistance to antimicrobials
Frontiers in Microbiology, 2012Co-Authors: Jose L MartinezAbstract:The study of Antibiotic Resistance has been historically concentrated on the analysis of bacterial pathogens and on the consequences of acquiring Resistance for human health. The development of Antibiotic Resistance is of course extremely relevant from the clinical point of view, because it can compromise the treatment of infectious diseases as well as other advanced therapeutic procedures as transplantation or anticancer therapy that involve immunosuppression and thus require robust anti-infective preventive therapies. Nevertheless, the studies on Antibiotic Resistance should not be confined to clinical-associated ecosystems. It was evident soon after introducing Antibiotics for human therapy, that bacteria were able to develop Resistance, not just as the consequence of mutations in the targets of Antibiotics, but by acquiring genes conferring Resistance to antimicrobials (Abraham and Chain, 1940). Since those genes were not present before in the human bacterial pathogens, the only suitable source for them was the environmental microbiota, and indeed the presence of R-factors (Resistance plasmids) in pristine environments without any record of contact with Antibiotics was described in the first studies of Antibiotic Resistance in the field (Gardner et al., 1969).
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mutation frequencies and Antibiotic Resistance
Antimicrobial Agents and Chemotherapy, 2000Co-Authors: Jose L Martinez, Fernando BaqueroAbstract:Antibiotic Resistance can be achieved by horizontal acquisition of Resistance genes (carried by plasmids or transposons), by recombination of foreign DNA into the chromosome, or by mutations in different chromosomal loci ([15][1]). In studies of molecular evolutionary biology, the term mutation rate
Mark A Valasek - One of the best experts on this subject based on the ideXlab platform.
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review article the global emergence of helicobacter pylori Antibiotic Resistance
Alimentary Pharmacology & Therapeutics, 2016Co-Authors: Irene Thung, H Aramin, Vera Vavinskaya, Samir Gupta, Jason Y Park, Sheila E Crowe, Mark A ValasekAbstract:Summary Background Helicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma. Aim To review recent trends in H. pylori Antibiotic Resistance rates, and to discuss diagnostics and treatment paradigms. Methods A PubMed literature search using the following keywords: Helicobacter pylori, Antibiotic Resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing. Results The prevalence of bacterial Antibiotic Resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin Resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas Resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other Antibiotics show similar trends, although less pronounced. Conclusions Since the choice of empiric therapies should be predicated on accurate information regarding Antibiotic Resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric Antibiotic therapy but also inform the development of better methods to identify H. pylori Antibiotic Resistance at diagnosis. Patient-specific tailoring of effective Antibiotic treatment strategies may lead to reduced treatment failures and less Antibiotic Resistance.
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review article the global emergence of helicobacter pylori Antibiotic Resistance
Alimentary Pharmacology & Therapeutics, 2016Co-Authors: Irene Thung, H Aramin, Vera Vavinskaya, Samir Gupta, Jason Y Park, Sheila E Crowe, Mark A ValasekAbstract:Author(s): Thung, I; Aramin, H; Vavinskaya, V; Gupta, S; Park, JY; Crowe, SE; Valasek, MA | Abstract: BackgroundHelicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma.AimTo review recent trends in H. pylori Antibiotic Resistance rates, and to discuss diagnostics and treatment paradigms.MethodsA PubMed literature search using the following keywords: Helicobacter pylori, Antibiotic Resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing.ResultsThe prevalence of bacterial Antibiotic Resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin Resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas Resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other Antibiotics show similar trends, although less pronounced.ConclusionsSince the choice of empiric therapies should be predicated on accurate information regarding Antibiotic Resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric Antibiotic therapy but also inform the development of better methods to identify H. pylori Antibiotic Resistance at diagnosis. Patient-specific tailoring of effective Antibiotic treatment strategies may lead to reduced treatment failures and less Antibiotic Resistance.
Irene Thung - One of the best experts on this subject based on the ideXlab platform.
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review article the global emergence of helicobacter pylori Antibiotic Resistance
Alimentary Pharmacology & Therapeutics, 2016Co-Authors: Irene Thung, H Aramin, Vera Vavinskaya, Samir Gupta, Jason Y Park, Sheila E Crowe, Mark A ValasekAbstract:Summary Background Helicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma. Aim To review recent trends in H. pylori Antibiotic Resistance rates, and to discuss diagnostics and treatment paradigms. Methods A PubMed literature search using the following keywords: Helicobacter pylori, Antibiotic Resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing. Results The prevalence of bacterial Antibiotic Resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin Resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas Resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other Antibiotics show similar trends, although less pronounced. Conclusions Since the choice of empiric therapies should be predicated on accurate information regarding Antibiotic Resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric Antibiotic therapy but also inform the development of better methods to identify H. pylori Antibiotic Resistance at diagnosis. Patient-specific tailoring of effective Antibiotic treatment strategies may lead to reduced treatment failures and less Antibiotic Resistance.
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review article the global emergence of helicobacter pylori Antibiotic Resistance
Alimentary Pharmacology & Therapeutics, 2016Co-Authors: Irene Thung, H Aramin, Vera Vavinskaya, Samir Gupta, Jason Y Park, Sheila E Crowe, Mark A ValasekAbstract:Author(s): Thung, I; Aramin, H; Vavinskaya, V; Gupta, S; Park, JY; Crowe, SE; Valasek, MA | Abstract: BackgroundHelicobacter pylori is one of the most prevalent global pathogens and can lead to gastrointestinal disease including peptic ulcers, gastric marginal zone lymphoma and gastric carcinoma.AimTo review recent trends in H. pylori Antibiotic Resistance rates, and to discuss diagnostics and treatment paradigms.MethodsA PubMed literature search using the following keywords: Helicobacter pylori, Antibiotic Resistance, clarithromycin, levofloxacin, metronidazole, prevalence, susceptibility testing.ResultsThe prevalence of bacterial Antibiotic Resistance is regionally variable and appears to be markedly increasing with time in many countries. Concordantly, the antimicrobial eradication rate of H. pylori has been declining globally. In particular, clarithromycin Resistance has been rapidly increasing in many countries over the past decade, with rates as high as approximately 30% in Japan and Italy, 50% in China and 40% in Turkey; whereas Resistance rates are much lower in Sweden and Taiwan, at approximately 15%; there are limited data in the USA. Other Antibiotics show similar trends, although less pronounced.ConclusionsSince the choice of empiric therapies should be predicated on accurate information regarding Antibiotic Resistance rates, there is a critical need for determination of current rates at a local scale, and perhaps in individual patients. Such information would not only guide selection of appropriate empiric Antibiotic therapy but also inform the development of better methods to identify H. pylori Antibiotic Resistance at diagnosis. Patient-specific tailoring of effective Antibiotic treatment strategies may lead to reduced treatment failures and less Antibiotic Resistance.
Thomas Heberer - One of the best experts on this subject based on the ideXlab platform.
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human health risk assessment hhra for environmental development and transfer of Antibiotic Resistance
Environmental Health Perspectives, 2013Co-Authors: Nicholas J Ashbolt, Alejandro Amezquita, Thomas Backhaus, Peter Borriello, Kristian K Brandt, Peter Collignon, Anja Coors, Rita Finley, William H Gaze, Thomas HebererAbstract:Background: Only recently has the environment been clearly implicated in the risk of Antibiotic Resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks. Objective: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of Antibiotic treatment caused by Antibiotic-resistant pathogens. Methods: The authors participated in a workshop held 4–8 March 2012 in Quebec, Canada, to define the scope and objectives of an environmental assessment of Antibiotic-Resistance risks to human health. We focused on key elements of environmental-Resistance-development “hot spots,” exposure assessment (unrelated to food), and dose response to characterize risks that may improve Antibiotic-Resistance management options. Discussion: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental Antibiotic Resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of Antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental “hot spot” compartments; and c) modifying traditional dose–response approaches to address doses of ARB for various health outcomes and pathways. Conclusions: We propose that environmental aspects of Antibiotic-Resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental Antibiotic Resistance that informs risk managers. Citation: Ashbolt NJ, Amezquita A, Backhaus T, Borriello P, Brandt KK, Collignon P, Coors A, Finley R, Gaze WH, Heberer T, Lawrence JR, Larsson DG, McEwen SA, Ryan JJ, Schonfeld J, Silley P, Snape JR, Van den Eede C, Topp E. 2013. Human health risk assessment (HHRA) for environmental development and transfer of Antibiotic Resistance. Environ Health Perspect 121:993–1001; http://dx.doi.org/10.1289/ehp.1206316
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human health risk assessment hhra for environmental development and transfer of Antibiotic Resistance
Environmental Health Perspectives, 2013Co-Authors: Nicholas J Ashbolt, Alejandro Amezquita, Thomas Backhaus, Peter Borriello, Kristian K Brandt, Peter Collignon, Anja Coors, Rita Finley, William H Gaze, Thomas HebererAbstract:Background: Only recently has the environment been clearly implicated in the risk of Antibiotic Resistance to clinical outcome, but to date there have been few documented approaches to formally assess these risks. Objective: We examined possible approaches and sought to identify research needs to enable human health risk assessments (HHRA) that focus on the role of the environment in the failure of Antibiotic treatment caused by Antibiotic-resistant pathogens. Methods: The authors participated in a workshop held 4–8 March 2012 in Quebec, Canada, to define the scope and objectives of an environmental assessment of Antibiotic-Resistance risks to human health. We focused on key elements of environmental-Resistance-development “hot spots,” exposure assessment (unrelated to food), and dose response to characterize risks that may improve Antibiotic-Resistance management options. Discussion: Various novel aspects to traditional risk assessments were identified to enable an assessment of environmental Antibiotic Resistance. These include a) accounting for an added selective pressure on the environmental resistome that, over time, allows for development of Antibiotic-resistant bacteria (ARB); b) identifying and describing rates of horizontal gene transfer (HGT) in the relevant environmental “hot spot” compartments; and c) modifying traditional dose–response approaches to address doses of ARB for various health outcomes and pathways. Conclusions: We propose that environmental aspects of Antibiotic-Resistance development be included in the processes of any HHRA addressing ARB. Because of limited available data, a multicriteria decision analysis approach would be a useful way to undertake an HHRA of environmental Antibiotic Resistance that informs risk managers. Citation: Ashbolt NJ, Amezquita A, Backhaus T, Borriello P, Brandt KK, Collignon P, Coors A, Finley R, Gaze WH, Heberer T, Lawrence JR, Larsson DG, McEwen SA, Ryan JJ, Schonfeld J, Silley P, Snape JR, Van den Eede C, Topp E. 2013. Human health risk assessment (HHRA) for environmental development and transfer of Antibiotic Resistance. Environ Health Perspect 121:993–1001; http://dx.doi.org/10.1289/ehp.1206316