Identification of mcr-10 carried by self-transmissible plasmids and chromosome in Enterobacter roggenkampii strains isolated from hospital sewage water

Abstract

The recent emergence of plasmid-borne mobilized colistin resistance (mcr) genes largely challenges the clinical use of colistin. Monitoring the distribution of mcr genes in environment is important for aiding to develop effective control measures. In this study, we aimed to evaluate the occurrence of a recent reported mcr variant, mcr-10, in hospital sewage water. mcr-10 was identified in three Enterobacter roggenkampii strains with high-level colistin resistance (MIC ≥ 16 mg/L). The three strains were assigned to different sequence types suggesting a sporadic dissemination of mcr-10 in the sewage water. Pairwise comparisons of the predicted protein structures of ten mcr homologues revealed that MCR-10 shares a higher similarity with MCR-3, MCR-4, MCR-7, and MCR-9. Overexpression in Escherichia coli Top10 showed that the activity of mcr-10 against colistin is lower than that of mcr-9. mcr-10 expression can be specifically induced by colistin, and it was co-upregulated with phoPQ to mediate the high-level colistin resistance. The mcr-10 gene was detected on self-transmissible plasmids in two isolates and on the chromosome in the other one. Blasting in Genbank suggested that the two mcr-10-bearing plasmids (pECL981-1 and pECL983-1) were novel plasmids, and replicon typing showed that they belong to IncFIB-FII and IncFIB, respectively. Plasmid-curing assay evidence that pECL981-1 was lack of fitness cost for the host. Three novel types of the genetic context were found for the mcr-10 gene in the three isolates. The structure xerC-mcr10 was dominant in mcr-10-positive genomes (39/42) retrieved in Genbank, suggesting that xerC might be involved in the mobilization of mcr-10. To our knowledge, this is the first report of mcr-10-producing E. roggenkampii detected in hospital sewage water. Our study highlights that continuous monitoring of mcr genes in hospital sewage water is imperative for understanding and tackling the dissemination.

Keywords: Antibiotic resistance; Colistin; Enterobacter roggenkampii; Mobilized colistin resistance; Plasmid-mediated resistance; mcr-10.