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      The fitness costs of antibiotic resistance mutations

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          Abstract

          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.

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          Most cited references68

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          The competitive cost of antibiotic resistance in Mycobacterium tuberculosis.

          Mathematical models predict that the future of the multidrug-resistant tuberculosis epidemic will depend on the fitness cost of drug resistance. We show that in laboratory-derived mutants of Mycobacterium tuberculosis, rifampin resistance is universally associated with a competitive fitness cost and that this cost is determined by the specific resistance mutation and strain genetic background. In contrast, we demonstrate that prolonged patient treatment can result in multidrug-resistant strains with no fitness defect and that strains with low- or no-cost resistance mutations are also the most frequent among clinical isolates.
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            R: A language and enviornment for statistical computing

            (2010)
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              Compensatory mutations, antibiotic resistance and the population genetics of adaptive evolution in bacteria.

              In the absence of the selecting drugs, chromosomal mutations for resistance to antibiotics and other chemotheraputic agents commonly engender a cost in the fitness of microorganisms. Recent in vivo and in vitro experimental studies of the adaptation to these "costs of resistance" in Escherichia coli, HIV, and Salmonella typhimurium found that evolution in the absence of these drugs commonly results in the ascent of mutations that ameliorate these costs, rather than higher-fitness, drug-sensitive revertants. To ascertain the conditions under which this compensatory evolution, rather than reversion, will occur, we did computer simulations, in vitro experiments, and DNA sequencing studies with low-fitness rpsL (streptomycin-resistant) mutants of E. coli with and without mutations that compensate for the fitness costs of these ribosomal protein mutations. The results of our investigation support the hypothesis that in these experiments, the ascent of intermediate-fitness compensatory mutants, rather than high-fitness revertants, can be attributed to higher rates of compensatory mutations relative to that of reversion and to the numerical bottlenecks associated with serial passage. We argue that these bottlenecks are intrinsic to the population dynamics of parasitic and commensal microbes and discuss the implications of these results to the problem of drug resistance and adaptive evolution in parasitic and commmensal microorganisms in general.

                Author and article information

                Journal
                Evol Appl
                Evol Appl
                eva
                Evolutionary Applications
                Blackwell Publishing Ltd (Oxford, UK )
                1752-4571
                1752-4571
                March 2015
                27 August 2014
                : 8
                : 3
                : 273-283
                Affiliations
                [1 ]Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa Ottawa, ON, Canada
                [2 ]Department of Biology, Carleton University Ottawa, ON, Canada
                Author notes
                Anita H. Melnyk, Department of Biology, University of Ottawa, 30 Marie-Curie Priv., Ottawa, ON K1N 6N5, Canada. Tel.: +1 613 562 5800 ext: 2066; fax: +1 613 562 5486; e-mail: anita.melnyk@ 123456uottawa.ca
                Article
                10.1111/eva.12196
                4380921
                25861385
                522dd35a-e673-4f19-adee-a26b8e61ecb7
                © 2015 John Wiley & Sons Ltd

                This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 February 2014
                : 10 July 2014
                Categories
                Reviews and Syntheses

                Evolutionary Biology
                adaptation,antibiotic resistance,fitness
                Evolutionary Biology
                adaptation, antibiotic resistance, fitness

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