Epistasis decreases with increasing antibiotic pressure but not temperature

Author:

Ghenu Ana-HerminaORCID,Amado AndréORCID,Gordo IsabelORCID,Bank ClaudiaORCID

Abstract

AbstractPredicting mutational effects is essential for the control of antibiotic resistance (ABR). Predictions are difficult when there are strong genotype-by-environment (G×E), gene-by-gene (G×G or epistatic), or gene- by-gene-by-environment (G×G×E) interactions. We quantified G×G×E effects inEscherichia coliacross 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 across a complete 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.

Publisher

Cold Spring Harbor Laboratory

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1. Epistasis decreases with increasing antibiotic pressure but not temperature;Philosophical Transactions of the Royal Society B: Biological Sciences;2023-04-03

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