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The fitness cost of horizontally transferred and mutational antimicrobial resistance in Escherichia coli

Antimicrobial resistance (AMR) in bacteria implies a tradeoff between the benefit of resistance under antimicrobial selection pressure and the incurred fitness cost in the absence of antimicrobials. The fitness cost of a resistance determinant is expected to depend on its genetic support, such as a...

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Autores principales: Vanacker, Marie, Lenuzza, Natacha, Rasigade, Jean-Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348881/
https://www.ncbi.nlm.nih.gov/pubmed/37455716
http://dx.doi.org/10.3389/fmicb.2023.1186920
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author Vanacker, Marie
Lenuzza, Natacha
Rasigade, Jean-Philippe
author_facet Vanacker, Marie
Lenuzza, Natacha
Rasigade, Jean-Philippe
author_sort Vanacker, Marie
collection PubMed
description Antimicrobial resistance (AMR) in bacteria implies a tradeoff between the benefit of resistance under antimicrobial selection pressure and the incurred fitness cost in the absence of antimicrobials. The fitness cost of a resistance determinant is expected to depend on its genetic support, such as a chromosomal mutation or a plasmid acquisition, and on its impact on cell metabolism, such as an alteration in an essential metabolic pathway or the production of a new enzyme. To provide a global picture of the factors that influence AMR fitness cost, we conducted a systematic review and meta-analysis focused on a single species, Escherichia coli. By combining results from 46 high-quality studies in a multilevel meta-analysis framework, we find that the fitness cost of AMR is smaller when provided by horizontally transferable genes such as those encoding beta-lactamases, compared to mutations in core genes such as those involved in fluoroquinolone and rifampicin resistance. We observe that the accumulation of acquired AMR genes imposes a much smaller burden on the host cell than the accumulation of AMR mutations, and we provide quantitative estimates of the additional cost of a new gene or mutation. These findings highlight that gene acquisition is more efficient than the accumulation of mutations to evolve multidrug resistance, which can contribute to the observed dominance of horizontally transferred genes in the current AMR epidemic.
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spelling pubmed-103488812023-07-15 The fitness cost of horizontally transferred and mutational antimicrobial resistance in Escherichia coli Vanacker, Marie Lenuzza, Natacha Rasigade, Jean-Philippe Front Microbiol Microbiology Antimicrobial resistance (AMR) in bacteria implies a tradeoff between the benefit of resistance under antimicrobial selection pressure and the incurred fitness cost in the absence of antimicrobials. The fitness cost of a resistance determinant is expected to depend on its genetic support, such as a chromosomal mutation or a plasmid acquisition, and on its impact on cell metabolism, such as an alteration in an essential metabolic pathway or the production of a new enzyme. To provide a global picture of the factors that influence AMR fitness cost, we conducted a systematic review and meta-analysis focused on a single species, Escherichia coli. By combining results from 46 high-quality studies in a multilevel meta-analysis framework, we find that the fitness cost of AMR is smaller when provided by horizontally transferable genes such as those encoding beta-lactamases, compared to mutations in core genes such as those involved in fluoroquinolone and rifampicin resistance. We observe that the accumulation of acquired AMR genes imposes a much smaller burden on the host cell than the accumulation of AMR mutations, and we provide quantitative estimates of the additional cost of a new gene or mutation. These findings highlight that gene acquisition is more efficient than the accumulation of mutations to evolve multidrug resistance, which can contribute to the observed dominance of horizontally transferred genes in the current AMR epidemic. Frontiers Media S.A. 2023-06-30 /pmc/articles/PMC10348881/ /pubmed/37455716 http://dx.doi.org/10.3389/fmicb.2023.1186920 Text en Copyright © 2023 Vanacker, Lenuzza and Rasigade. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Vanacker, Marie
Lenuzza, Natacha
Rasigade, Jean-Philippe
The fitness cost of horizontally transferred and mutational antimicrobial resistance in Escherichia coli
title The fitness cost of horizontally transferred and mutational antimicrobial resistance in Escherichia coli
title_full The fitness cost of horizontally transferred and mutational antimicrobial resistance in Escherichia coli
title_fullStr The fitness cost of horizontally transferred and mutational antimicrobial resistance in Escherichia coli
title_full_unstemmed The fitness cost of horizontally transferred and mutational antimicrobial resistance in Escherichia coli
title_short The fitness cost of horizontally transferred and mutational antimicrobial resistance in Escherichia coli
title_sort fitness cost of horizontally transferred and mutational antimicrobial resistance in escherichia coli
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10348881/
https://www.ncbi.nlm.nih.gov/pubmed/37455716
http://dx.doi.org/10.3389/fmicb.2023.1186920
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