Characterization of a clinicalEnterobacter hormaecheistrain belonging to epidemic clone ST418 co-carryingblaNDM-1,blaIMP-4and mcr-9.1

An Enterobacter hormaechei isolate (ECL-90) simultaneously harboring bla NDM-1 , bla IMP-4 and mcr-9 . 1 was recovered from the secretion specimen of a 24-year-old male patient in a tertiary hospital in China. The whole genome sequencing of this isolate was complete, and 4 circular plasmids with variable sizes were detected. MLST analysis assigned the isolate to ST418, known as a carbapenemase-producing epidemic clone in China. bla IMP-4 and mcr-9 . 1 genes were co-carried on an IncHI2/2A plasmid (pECL-90-2) and bla NDM-1 was harbored by an IncX3 plasmid (pECL-90-3). The genetic context of mcr-9 . 1 was identified as a prevalent structure, “ rcnR-rcnA-pcoE-pcoS -IS 903 - mcr-9-wbuC ”, which is a relatively unitary model involved in the mobilization of mcr-9 . Meanwhile, bla NDM-1 gene was detected within a globally widespread structure known as NDM-GE-U.S (“IS Aba125 – bla NDM-1 – bla MBL ”). Our study warrants that the convergence of genes mediating resistance to last-resort antibiotics in epidemic clones would largely facilitate their widespread in clinical settings, thus representing a potential challenge to clinical treatment and public health. Importance Carbapenemase-producing Enterobacteriaceae (CPE) spread at a high rate and colistin is the last-resort therapeutic for the infection caused by CPE. However, the emergence of plasmid-borne mcr genes highly facilitates the wide dissemination of colistin resistance, thus largely threatens the clinical use of colistin. Here, we for the first time characterized a clinical Enterobacter hormaechei strain co-producing bla NDM-1 , bla IMP-4 and mcr -9.1 belonging to an epidemic clone (ST418). The accumulation of genes mediating resistance to last-resort antibiotics in epidemic clones would largely facilitate their widespread in clinical settings, which may cause disastrous consequence with respect to antimicrobial resistance. Understanding how resistance genes were accumulated in a single strain could help us to track the evolutionary trajectory of drug resistance. Our finding highlights the importance of surveillance on the epidemic potential of colistin-resistant CPE, and effective infection control measures to prevent the resistance dissemination.