Epistasis decreases with increasing antibiotic pressure but not temperature
Publisher DOI
PubMed ID
37004727
Abstract
Predicting mutational effects is essential for the control of antibiotic resistance (ABR). Predictions are difficult when there are strong genotype-byenvironment (G× E), gene-by-gene (G ×G or epistatic) or gene-by-geneby-environment (G ×G× E) interactions. We quantified G×G× E effects in Escherichia coli across environmental gradients. We created intergenic fitness landscapes using gene knock-outs and single-nucleotide ABR mutations previously identified to vary in the extent of G× E effects in our environments of interest. Then,we measured competitive fitness acrossacomplete combinatorial
set of temperature and antibiotic dosage gradients. In this way, we assessed the predictability of 15 fitness landscapes across 12 different but related environments. We found G×G interactions and rugged fitness landscapes in the absence of antibiotic, but as antibiotic concentration increased, the fitness effects of ABR genotypes quickly overshadowed those of gene knock-outs, and the
landscapes became smoother. Our work reiterates that some single mutants, like those conferring resistance or susceptibility to antibiotics, have consistent effects across genetic backgrounds in stressful environments. Thus, although epistasis may reduce the predictability of evolution in benign environments, evolution may be more predictable in adverse environments. This article is part of the theme issue ‘Interdisciplinary approaches to predicting evolutionary biology’.
set of temperature and antibiotic dosage gradients. In this way, we assessed the predictability of 15 fitness landscapes across 12 different but related environments. We found G×G interactions and rugged fitness landscapes in the absence of antibiotic, but as antibiotic concentration increased, the fitness effects of ABR genotypes quickly overshadowed those of gene knock-outs, and the
landscapes became smoother. Our work reiterates that some single mutants, like those conferring resistance or susceptibility to antibiotics, have consistent effects across genetic backgrounds in stressful environments. Thus, although epistasis may reduce the predictability of evolution in benign environments, evolution may be more predictable in adverse environments. This article is part of the theme issue ‘Interdisciplinary approaches to predicting evolutionary biology’.
Date Issued
2023-04-03
Publication Type
Article
Subject(s)
Subjects
environmental interactions
•
cryptic epistasis
•
RNA polymerase B (rpoB)
•
genetic interactions
•
rifampicin
Language(s)
en
Author(s)
Gordo, Isabel |
Journal
Philosophical transactions of the Royal Society. Series B - biological sciences
Publisher
Royal Society of London
ISSN
0962-8436
Access(Rights)
open.access