Predictable Phenotypes of Antibiotic Resistance Mutations

MBio
M Knopp, Dan I Andersson

Abstract

Antibiotic-resistant bacteria represent a major threat to our ability to treat bacterial infections. Two factors that determine the evolutionary success of antibiotic resistance mutations are their impact on resistance level and the fitness cost. Recent studies suggest that resistance mutations commonly show epistatic interactions, which would complicate predictions of their stability in bacterial populations. We analyzed 13 different chromosomal resistance mutations and 10 host strains of Salmonella enterica and Escherichia coli to address two main questions. (i) Are there epistatic interactions between different chromosomal resistance mutations? (ii) How does the strain background and genetic distance influence the effect of chromosomal resistance mutations on resistance and fitness? Our results show that the effects of combined resistance mutations on resistance and fitness are largely predictable and that epistasis remains rare even when up to four mutations were combined. Furthermore, a majority of the mutations, especially target alteration mutations, demonstrate strain-independent phenotypes across different species. This study extends our understanding of epistasis among resistance mutations and shows that interactions ...Continue Reading

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Citations

Nov 2, 2018·Journal of Clinical Microbiology·Michelle SuTimothy D Read
May 7, 2019·Molecular Biology and Evolution·Gábor ApjokBálint Csörgő
Jun 23, 2019·Molecular Biology and Evolution·Sara Hernando-AmadoJosé Luis Martínez
Jan 26, 2020·FEMS Microbiology Reviews·Dan I AnderssonTone Tønjum
Nov 9, 2018·Frontiers in Genetics·Fernando Sanz-GarcíaJosé L Martínez
May 28, 2020·MBio·Michelle R ScribnerVaughn S Cooper
Jul 8, 2020·Nature Ecology & Evolution·Luís Leónidas CardosoIsabel Gordo
Jan 8, 2021·PLoS Genetics·Michael KnoppDan I Andersson
Jan 9, 2021·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Abdelaziz TouatiAssia Mairi
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Jun 4, 2021·Cell Death & Disease·Yanfei LiJunwei Shen
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Jul 1, 2021·Clinical Microbiology Reviews·F BaqueroT M Coque
Jul 10, 2019·ACS Infectious Diseases·Sol R MartínezAndrés M Durantini

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Methods Mentioned

BETA
Bioscreen
PCR

Software Mentioned

ModelFinder
IQ
TREE
CLC Genomics Workbench
MAFFT
Adobe Illustrator
FigTree

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