E. coli rifampicin antibiotic resistance and gene deletion fitness landscapes

Predicting mutational effects is essential for the control of antibiotic resistance (ABR). Predictions are difficult when there are strong genotype-by-environment (GxE), gene-by-gene (GxG or epistatic), or gene-by-gene-by-environment (GxGxE) interactions. We quantified GxGxE effects in Escherichia coli across a complete combinatorial set of two environmental gradients, rifampicin antibiotic concentration and high temperature. We genetically engineered intergenic fitness landscapes by combining three known ABR mutations in the rpoB gene with five whole gene deletions, resulting in 24 GFP-labeled genotypes (one WT, eight single mutants, and 15 double mutants) that were competed against a common mCherry-labeled reference genotype to get competitive fitness in 12 abiotic environments. This BioProject contains the whole-genome sequencing data for the 25 genotypes that were used to create the fitness landscapes. The pre-print manuscript is available at https://doi.org/10.1101/2022.09.01.506172