Colistin resistance in human faecal Escherichia coli as the result of two distinct evolutionary pathways in France. Colistin resistance in Escherichia coli

The emergence of colistin resistance among Escherichia coli may constitute a major threat. Beyond plasmid-encoded resistance (mcr genes) prevalence in strain collections, large epidemiological studies to estimate the human burden of the colistin-resistant E. coli gut carriage and its origin are lacking. During a three month-period (2016-2017), we prospectively screened patients in six University hospitals located in the Paris area for rectal carriage of colistin-resistant E. coli using a selective medium, a biochemical confirmatory test and MIC determination. Whole-genome sequencing of the resistant strains and their corresponding plasmids was performed. Among the 1,217 screened patients, 12.5% (152) carried a colistin-resistant E. coli strain. The mcr-1 gene was identified in only seven isolates (4.6%) onto different plasmid scaffolds. According to the databases, the genetic background of these MCR-1 producers argued for an animal origin. Conversely, the remaining 145 colistin-resistant E. coli harboured a phylogenetic distribution corresponding to human gut commensal/clinical population structure (including B2 and D phylogroup predominance); 64% of those isolates harboured convergent mutations in the PmrA and PmrB proteins, constituting a two-component system previously shown to be associated with colistin resistance. We showed that the occurrence at a relatively high rate of colistin resistance in human faecal E. coli is the result of two distinct evolutionary pathways, namely the occurrence of an endogenous E. coli population harbouring chromosomal mutations, and rare acquisition of exogenous mcr-1-bearing strains likely of animal origin. The selective pressures leading to such phenomenon need to be identified to develop preventing strategies.