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Idiosyncratic Fitness Costs of Ampicillin-Resistant Mutants Derived from a Long-Term Experiment with Escherichia coli

Antibiotic resistance is a growing concern that has prompted a renewed focus on drug discovery, stewardship, and evolutionary studies of the patterns and processes that underlie this phenomenon. A resistant strain’s competitive fitness relative to its sensitive counterparts in the absence of drug ca...

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Autores principales: Jordan, Jalin A., Lenski, Richard E., Card, Kyle J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944548/
https://www.ncbi.nlm.nih.gov/pubmed/35326810
http://dx.doi.org/10.3390/antibiotics11030347
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author Jordan, Jalin A.
Lenski, Richard E.
Card, Kyle J.
author_facet Jordan, Jalin A.
Lenski, Richard E.
Card, Kyle J.
author_sort Jordan, Jalin A.
collection PubMed
description Antibiotic resistance is a growing concern that has prompted a renewed focus on drug discovery, stewardship, and evolutionary studies of the patterns and processes that underlie this phenomenon. A resistant strain’s competitive fitness relative to its sensitive counterparts in the absence of drug can impact its spread and persistence in both clinical and community settings. In a prior study, we examined the fitness of tetracycline-resistant clones that evolved from five different Escherichia coli genotypes, which had diverged during a long-term evolution experiment. In this study, we build on that work to examine whether ampicillin-resistant mutants are also less fit in the absence of the drug than their sensitive parents, and whether the cost of resistance is constant or variable among independently derived lines. Like the tetracycline-resistant lines, the ampicillin-resistant mutants were often less fit than their sensitive parents, with significant variation in the fitness costs among the mutants. This variation was not associated with the level of resistance conferred by the mutations, nor did it vary across the different parental backgrounds. In our earlier study, some of the variation in fitness costs associated with tetracycline resistance was explained by the effects of different mutations affecting the same cellular pathway and even the same gene. In contrast, the variance among the ampicillin-resistant mutants was associated with different sets of target genes. About half of the resistant clones suffered large fitness deficits, and their mutations impacted major outer-membrane proteins or subunits of RNA polymerases. The other mutants experienced little or no fitness costs and with, one exception, they had mutations affecting other genes and functions. Our findings underscore the importance of comparative studies on the evolution of antibiotic resistance, and they highlight the nuanced processes that shape these phenotypes.
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spelling pubmed-89445482022-03-25 Idiosyncratic Fitness Costs of Ampicillin-Resistant Mutants Derived from a Long-Term Experiment with Escherichia coli Jordan, Jalin A. Lenski, Richard E. Card, Kyle J. Antibiotics (Basel) Article Antibiotic resistance is a growing concern that has prompted a renewed focus on drug discovery, stewardship, and evolutionary studies of the patterns and processes that underlie this phenomenon. A resistant strain’s competitive fitness relative to its sensitive counterparts in the absence of drug can impact its spread and persistence in both clinical and community settings. In a prior study, we examined the fitness of tetracycline-resistant clones that evolved from five different Escherichia coli genotypes, which had diverged during a long-term evolution experiment. In this study, we build on that work to examine whether ampicillin-resistant mutants are also less fit in the absence of the drug than their sensitive parents, and whether the cost of resistance is constant or variable among independently derived lines. Like the tetracycline-resistant lines, the ampicillin-resistant mutants were often less fit than their sensitive parents, with significant variation in the fitness costs among the mutants. This variation was not associated with the level of resistance conferred by the mutations, nor did it vary across the different parental backgrounds. In our earlier study, some of the variation in fitness costs associated with tetracycline resistance was explained by the effects of different mutations affecting the same cellular pathway and even the same gene. In contrast, the variance among the ampicillin-resistant mutants was associated with different sets of target genes. About half of the resistant clones suffered large fitness deficits, and their mutations impacted major outer-membrane proteins or subunits of RNA polymerases. The other mutants experienced little or no fitness costs and with, one exception, they had mutations affecting other genes and functions. Our findings underscore the importance of comparative studies on the evolution of antibiotic resistance, and they highlight the nuanced processes that shape these phenotypes. MDPI 2022-03-06 /pmc/articles/PMC8944548/ /pubmed/35326810 http://dx.doi.org/10.3390/antibiotics11030347 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Jordan, Jalin A.
Lenski, Richard E.
Card, Kyle J.
Idiosyncratic Fitness Costs of Ampicillin-Resistant Mutants Derived from a Long-Term Experiment with Escherichia coli
title Idiosyncratic Fitness Costs of Ampicillin-Resistant Mutants Derived from a Long-Term Experiment with Escherichia coli
title_full Idiosyncratic Fitness Costs of Ampicillin-Resistant Mutants Derived from a Long-Term Experiment with Escherichia coli
title_fullStr Idiosyncratic Fitness Costs of Ampicillin-Resistant Mutants Derived from a Long-Term Experiment with Escherichia coli
title_full_unstemmed Idiosyncratic Fitness Costs of Ampicillin-Resistant Mutants Derived from a Long-Term Experiment with Escherichia coli
title_short Idiosyncratic Fitness Costs of Ampicillin-Resistant Mutants Derived from a Long-Term Experiment with Escherichia coli
title_sort idiosyncratic fitness costs of ampicillin-resistant mutants derived from a long-term experiment with escherichia coli
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8944548/
https://www.ncbi.nlm.nih.gov/pubmed/35326810
http://dx.doi.org/10.3390/antibiotics11030347
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