Emergence of a novel hybrid mcr-1-bearing plasmid in an NDM-7-producing ST167 Escherichia coli strain of clinical origin

Abstract

Colistin is considered as an antibiotic of ‘last resort’ for the treatment of lethal infections caused by carbapenem-resistant Enterobacterales (CRE), dissemination of plasmid-borne colistin resistance gene mcr-1, particularly into CRE, resulting in the emergence of strains that approach pan-resistance. A wide variety of plasmid types have been reported for carrying mcr-1. Among which, large IncHI2-type plasmids were multidrug-resistant (MDR) plasmids harbored multiple resistance determinants in addition to mcr-1. Herein, we characterized a novel hybrid IncHI2-like mcr-1-bearing plasmid in an NDM-7-producing ST167 Escherichia coli strain EC15-50 of clinical origin. Antimicrobial susceptibility testing showed E. coli EC15-50 exhibited an extensively drug-resistant (XDR) profile that only susceptible to amikacin and tigecycline. S1-PFGE, Southern hybridization and Whole-genome Sequencing (WGS) analysis identified a 46,161 bp blaNDM-7-harboring IncX3 plasmid pEC50-NDM7 and a 350,179 bp mcr-1-bearing IncHI2/HI2A/N/FII/FIA plasmid pEC15-MCR-50 in E. coli EC15-50. Sequence detail analysis revealed the type IV coupling protein (T4CP) gene was absent on pEC15-MCR-50, explaining that pEC15-MCR-50 was a non-conjugative plasmid. Comparative genetic analysis indicated the hybrid plasmid pEC15-MCR-50 was probably originated from pXGE1mcr-like IncHI2/HI2A/N plasmid and pSJ_94-like IncFII/FIA plasmid, and generated as a result of a replicative transposition process mediated by IS26. Currently, the prevalent mcr-1-carrying IncHI2 plasmids were rarely reported to be fused with other plasmids. The identification of the novel hybrid plasmid pEC15-MCR-50 in this study highlighted the importance of close surveillance for the emergence and dissemination of such fusion MDR plasmids, particularly in NDM-producing Enterobacterales.

Identification and Genomic Analyses of a Multidrug Resistant Avian Pathogenic Escherichia coli Coharboring mcr-1, blaTEM-176 and blaCTX-M-14 Genes

“…As the last line defense against MDR E. coli infections, colistin has been widely used to treat infections caused by CRE [3]. Additionally, as the poultry and swine industries accounted for 96% of total colistin sulfate livestock use [4], the presence of mcr in them provides evidence that colistin treatment has promoted the transmission of mcr, with livestock as the primary reservoir.…”

“…In this study, segment organized as IS1-IS6-tet(M)-tcpC-Tn3 and partial-MFS transporter-mph(A)-IS26 was found in the backbone of IncHI2-type conjugative plasmid different from MG656414.1 and MW815279.1. IS26 was indicated to be a reason for formation of mcr-1-bearing IncHI2/HI2A/N/ FII/FIA hybrid plasmid [3]. The tetracycline resistance gene tet (M) encodes a ribosomal protection protein that confers tetracycline resistance to a variety of bacterial species.…”

“…Colistin is a cationic amphiphilic lipopeptide antibacterial agent. As a last resort antimicrobial, colistin is an important antimicrobial for human treatment of Carbapenem-resistant Enterobacteriaceae (CRE) infections [3]. However, it has been widely used in livestock production, especially in pigs, for a long time [4].…”