Epistasis decreases with increasing antibiotic pressure but not temperature

Abstract

Predicting 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 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 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. This article is part of the theme issue ‘Interdisciplinary approaches to predicting evolutionary biology’.

Mechanistic causes of sign epistasis and its applications

“…Besides the inherent challenges of predicting phenotypes posed by sign epistasis, the potential influence of the environment adds further complexity. It has been demonstrated that the occurrence or magnitude of sign epistasis can be altered by the environment, including the presence of inducers or inhibitors ( Baier et al, 2023 ) and antibiotics ( Ghenu et al, 2023 ). Nevertheless, the impact of other environmental factors on sign epistasis remains unclear.…”

Regulation Transcriptional of Antibiotic Resistance Genes (ARGs) in Bacteria Isolated from WWTP

“…Furthermore, the adaptation of bacteria to high concentrations of antibiotics in their habitat will be favored in bacterial strains with genetic elements such as plasmids and integrons that allow them to survive in these conditions. A recent study where it was predicted how gene-by-gene by-environment (G × G × E) interactions affect the evolution of E. coli against pressure at various concentrations of antibiotics, it was shown that G × G interactions and rugged fitness landscapes in the absence of antibiotics, but as antibiotic concentration increased, the fitness effects of ABR genotypes quickly overshadowed those of gene knock-outs, and the landscapes became smoother [ 31 ], suggesting that the evolution of resistant bacteria to antibiotics is facilitated by extreme habitats (with the presence of antibiotics) [ 32 ].…”

Slc11 Synapomorphy: A Conserved 3D Framework Articulating Carrier Conformation Switch

“…Assuming that the h4 loss of D mutation altered MCg1 function, it seems plausible that it was compensated by an array of stabilizing mutations at various sites in the protein, fostering MCg1-specific divergence from its ancestral state [44]. Though epistatic drift through intramolecular interactions may render protein evolution less predictable [45], stressful and/or adverse environments exerting strong selective pressure can channel such a process [46]. This seems to be the case with the expansive divergence of the (D4XFA5) Bordetella-Achromobacter MCg1 clade wherein structural divergence suggests shifted constraints that could stabilize MCg1 functional evolution in these emerging bacterial spp.…”