New Variant of mcr-3 in an Extensively Drug-Resistant Escherichia coli Clinical Isolate Carrying mcr-1 and blaNDM-5

Abstract

A colistin- and carbapenem-resistant Escherichia coli clinical isolate was found to carry two plasmid-borne colistin-resistant genes, mcr-1 and the newly identified mcr-3, and a carbapenemase gene, bla_NDM-5mcr-3 is a new variant (mcr-3.5) in the isolate and encodes three amino acid substitutions compared with the original MCR-3. mcr-3 was carried by a TnAs3-like transposon on a self-transmissible IncP plasmid in the isolate, highlighting that mcr-3 may have widely spread.

Keywords: Enterobacteriaceae; Escherichia coli; colistin; plasmids; resistance.

FIG 1

The genetic context of mcr-3 on pMCR3_LL123 (second from top). The genetic context of mcr-3 on pWJ1 (top), that of the truncated mcr-3 on pMCR_1511 (third from top), and the corresponding region on non-mcr-3-carrying plasmid pMCR_1622 (bottom) are shown for comparison. The 5-bp direct repeats (DRs) characteristic of the transposition of Tn3 family transposons, including TnAs3 in this case, are indicated. dgkA refers to a gene encoding diacylglycerol kinase. The numbers represent genes or mobile genetic elements, including: 1, an open reading frame (ORF) of unknown function, which is broken into two parts (two 1Δ); 2, ISEnca1 truncated; 3, a gene encoding an NimA/NimC family protein, which is truncated with a 219-bp remnant on pWJ1 and a 24-bp remnant on pMCR3_LL123; 4, a gene encoding a DUF4942 domain-containing protein; 5, an ORF of unknown function; 6, a truncated (41-bp remnant) ISKpn40; 7, an ORF of unknown function; 8, an ORF of unknown function, which is interrupted by the composite transposon formed by ISApl1 carrying mcr-1 on pMCR_1511 and the ISApl1-mcr-1-orf element on pMCR_1622 with the 2-bp direct repeats (AC) characteristic of the insertion of ISApl1.