Escherichia coli genomic diversity within extra-intestinal acute infections argues for adaptive evolution at play

Adaptive processes in chronic bacterial infections are well described but much less is known about the processes at play during acute infections. Here, by sequencing seven randomly selected isolates per patient, we analyzed Escherichia coli populations from three acute extra-intestinal infections in adults (meningitis, pyelonephritis and peritonitis), in which a high mutation rate isolate or mutator isolate was found. The isolates of single patients displayed between a few dozen to more than two hundred independent mutations, with up to half being specific to the mutator isolate. Multiple signs of positive selection were evidenced: a high ratio of nonsynonymous to synonymous mutations (Ka/Ks) and strong mutational convergence within and between patients, some of them at loci well known for their adaptive potential such as rpoS, rbsR, fimH and fliC. For all patients, the mutator isolate was likely due to a large deletion of a methyl-directed mismatch repair gene and in two instances the deletion extended to genes involved in some genetic convergence, suggesting a potential co-selection. Intrinsic extra-intestinal virulence assessed in a mouse model of sepsis showed variable pattern of virulence ranging from non-mouse killer to mouse killer for the isolates of single patients. However genomic signature and gene inactivation experiments did not establish a link between a single gene and the capacity to kill mice, highlighting the complex and multi-factorial nature of the virulence. Altogether, these data indicate that E. coli isolates are adapting under strong selective pressure when colonizing an extra-intestinal site.