The population genomics of increased virulence and antibiotic resistance in human commensal Escherichia coli over 30 years in France

Abstract

ABSTRACTEscherichia coli is a commensal species of the lower intestine, but also a major pathogen causing intestinal and extra-intestinal infections. Most studies on genomic evolution of E. coli used isolates from infections, and/or focused on antibiotic resistance, but neglected the evolution of virulence. Here instead, we whole-genome sequenced a collection of 436 E. coli isolated from fecal samples of healthy adult volunteers in France between 1980 and 2010. These isolates were distributed among 159 sequence types (STs), the five most frequent being ST10 (15.6%), ST73 (5.5%) and ST95 (4.8%), ST69 (3.7%) and ST59 (3.7%), and 230 O:H serotypes. ST and serotype diversity increased over time. Comparison with 912 E. coli bacteremia isolates from similar region and time showed a greater diversity in commensal isolates. The O1, O2, O6 and O25-groups used in bioconjugate O-antigen vaccine were found in only 63% of the four main STs associated with a high risk of bacteremia (ST69, ST73, ST95 and ST131). In commensals, STs associated with a high risk of bacteremia increased in frequency. Both extra-intestinal virulence-associated genes and resistance to antibiotics increased in frequency. Evolution of virulence genes was driven by both clonal expansion of STs with more virulence genes, and increases in frequency within STs, whereas the evolution of resistance was dominated by increases in frequency within STs. This study provides a unique picture of the phylogenomic evolution of E. coli in its human commensal habitat over a 30-year period and suggests that the efficacy of O-antigen vaccines would be threatened by serotype replacement.