Colistin resistance in Parisian inpatient faecal Escherichia coli as the result of two distinct evolutionary pathways

Abstract

Background: Beyond plasmid-encoded resistance (mcr genes) prevalence in strain collections, large epidemiological studies to estimate the human burden of colistin-resistant Escherichia coli gut carriage are lacking. Objectives: To evaluate the prevalence of colistin-resistant E. coli carriage in inpatients and decipher the molecular support of resistance and the genetic background of the strains. Methods: During a 3 month period in 2017, we prospectively screened patients in six Parisian hospitals for rectal carriage of colistin-resistant E. coli using a selective medium, a biochemical confirmatory test and MIC determination. WGS of the resistant strains and their corresponding plasmids was performed. Results: Among the 1217 screened patients, 153 colistin-resistant E. coli strains were isolated from 152 patients (12.5%). The mcr-1 gene was identified in only seven isolates (4.6%) on different plasmid scaffolds. The genetic background of these MCR-1 producers argued for an animal origin. Conversely, the remaining 146 colistinresistant E. coli exhibited a phylogenetic distribution corresponding to human gut commensal/clinical population structure (B2 and D phylogroup predominance); 72.6% of those isolates harboured convergent mutations in the PmrA and PmrB proteins, constituting a two-component system shown to be associated with colistin resistance. Conclusions: We showed that the occurrence at a high rate of colistin resistance in human faecal E. coli is the result of two distinct evolutionary pathways, i.e. the occurrence of chromosomal mutations in an endogenous E. coli population and the rare acquisition of exogenous mcr-1-bearing strains probably of animal origin. The involved selective pressures need to be identified in order to develop preventative strategies.

mcr-9 , an Inducible Gene Encoding an Acquired Phosphoethanolamine Transferase in Escherichia coli, and Its Origin

“…In a recent prospective study performed in six different French university hospitals, despite the fact that the prevalence of fecal colistin-resistant E. coli carried by inpatients was found to be unexpectedly high (12.7%), the rate of MCR-1 producers was low (4.6% of the colistin-resistant isolates), and no other known MCR-like enzyme was identified (22). Two-thirds of the resistant isolates had mutations in the PmrA/PmrB chromosomally encoded two-component systems that are the likely sources of the resistance phenotype (22).…”

Characterization and rapid identification of phylogroup G in Escherichia coli, a lineage with high virulence and antibiotic resistance potential

“…To describe the diversity of the G phylogroup, we first searched in our personal collections for strains located in a phylogenetic tree of E. coli between the F and B2 phylogroups. The French collections used were: NILS (Bleibtreu et al ., ), Coliville (Massot et al ., ), ColiRed (Bourrel et al ., ), Guyana (Lescat et al ., ), Septicoli (http://clinicaltrials.gov, NCT02890901), COLOCOLI (La Combe et al ., ) and CEREMI (Burdet et al ., ), whereas the Australian collections represented strains recovered from humans, native vertebrates, poultry meat and water samples (Gordon and FitzGibbon, ; Gordon and Cowling, ; Power et al ., ; Blyton et al ., ; Blyton et al ., ; Vangchhia et al ., ). Inspection of the French and Australian strain collections yielded 19 strains from the French collections and 30 from the Australian collections.…”

Functional Characterization of a Miniature Inverted Transposable Element at the Origin of mcr-5 Gene Acquisition in Escherichia coli

“…No mcr-like genes were identified among the other colistin-resistant isolates. They likely possessed mutations in chromosomally encoded proteins involved in lipid A modifications, as recently reported, and are under investigation (18). All MCR-positive isolates were identified from a single pig farm, being the only one where colistin is frequently given for treating piglet diarrhea.…”