Fig. 8: AMR-associated genes have been found to impact numerous metabolic pathways in E. coli, many of them are also considered essential metabolic genes, and are prevalent across all metabolic pathways throughout the phylogeny of E. coli.

a An overview of the metabolic pathways affected by those AMR-associated genes significantly influencing reaction fluxes in E. coli. All genes annotated were found to have reduced the flux span through the metabolic system when knocked out, 11 of which were essential genes (i.e. gene knockouts were lethal in rich media). Significance was tested using hypergeometric enrichment tests (two-tailed) with the false discovery rate (FDR) threshold <1%. Genes highlighted in pink carried mutations that were selected in the E. coli ML models only, genes in red carried mutations that were selected in both the E. coli and S. enterica models, metabolic pathways are labelled in brown. b Heatmap showing, for each E. coli isolate (columns of the heatmap), whether the isolate contained an AMR-associated gene that if knocked out also significantly affected one or more metabolic pathways. The top part of the heatmap shows the phylogenetic relationship between each isolate. The first row of the heatmap indicates the phylogroup to which each isolate belongs. The subsequent rows indicate the metabolic pathways into which the genes were grouped, with only pathways significantly enriched with ML selected genes shown. Pink represents the presence of a mutated gene/accessory gene, blue represent the absence. For brevity, A and B1 clades, which showed presence of genes in every pathway, were collapsed.