Genetic characterization of blaNDM-harboring plasmids in carbapenem-resistant Escherichia coli from Myanmar

Abstract

The bacterial enzyme New Delhi metallo-β-lactamase hydrolyzes almost all β-lactam antibiotics, including carbapenems, which are drugs of last resort for severe bacterial infections. The spread of carbapenem-resistant Enterobacteriaceae that carry the New Delhi metallo-β-lactamase gene, blaNDM, poses a serious threat to public health. In this study, we genetically characterized eight carbapenem-resistant Escherichia coli isolates from a tertiary care hospital in Yangon, Myanmar. The eight isolates belonged to five multilocus-sequence types and harbored multiple antimicrobial-resistance genes, resulting in resistance against nearly all of the antimicrobial agents tested, except colistin and fosfomycin. Nine plasmids harboring blaNDM genes were identified from these isolates. Multiple blaNDM genes were found in the distinct Inc-replicon types of the following plasmids: an IncA/C2 plasmid harboring blaNDM-1 (n = 1), IncX3 plasmids harboring blaNDM-4 (n = 2) or blaNDM-7 (n = 1), IncFII plasmids harboring blaNDM-4 (n = 1) or blaNDM-5 (n = 3), and a multireplicon F plasmid harboring blaNDM-5 (n = 1). Comparative analysis highlighted the diversity of the blaNDM-harboring plasmids and their distinct characteristics, which depended on plasmid replicon types. The results indicate circulation of phylogenetically distinct strains of carbapenem-resistant E. coli with various plasmids harboring blaNDM genes in the hospital.

Plasmid evolution in carbapenemase‐producing Enterobacteriaceae: a review

“…This was shown in multiple A/C plasmids and in one IncF (pNDM‐EcoGN568) plasmid, which was identical to the A/C plasmids; the IncF plasmid only differed from the A/C plasmids by the number of ARG cassettes on the class 1 integron . Other NDM‐carrying plasmids, such as pM109‐FII and pGUE‐NDM, carry a 12‐kb ARG region that surrounds bla NDM . An additional gene cassette bracketed by two IS 26 elements and carrying bla TEM‐1 was found downstream of rmtB (a gene expressing an aminoglycoside resistance determinant) …”

“…Multiple plasmids have been reported, since 2012 and until recently, to carry NDM variants, particularly on IncFIB and IncFII plasmid types in K. pneumoniae and E. coli , respectively (Table and Fig. ) . Larger plasmids, such as pPMK1‐NDM (304.5 kb) and pNDM‐EcoGN568 (166.7 kb), are examples of NDM‐1–containing plasmids that contain other resistance determinants, including β‐lactamases, with pPMK1‐NDM containing a large conjugative transfer module .…”

“…These reports suggest that an essential role is played by IncX3 in the acquisition, emergence, and dissemination of bla NDM . IncX3 plasmids that have been associated with the spread of bla NDM include pEc2A (74.8 kb), pM213_X3 (43.5 kb), pNDM‐NJ‐IncX3 (39.5 kb), and pKW53T‐NDM (46.1 kb) . Other IncX3 plasmids recovered from Czech hospitals in Europe have been reported in E. cloacae isolates that express bla NDM‐4 .…”

“…bla NDM‐1 has been associated with A/C 2 plasmid types in different Enterobacteriaceae species; and recently, bla NDM‐4 was detected on A/C 2 plasmids . A/C 2 plasmids reported to carry bla NDM‐1 include pM214_AC2 (176 kb), pNDM‐EcoGN568 (166.7 kb), pNDM‐KN (162.7 kb), and pNDM‐PstGN576 (147.8 kb) . pNDM‐EcoGN568 is a multireplicon (IncF and A/C) circular plasmid reported to be identical to pNDM10‐0505, an A/C plasmid with the same size as pNDM‐EcoGN576 .…”

“…Other NDM‐carrying plasmids, such as pM109‐FII and pGUE‐NDM, carry a 12‐kb ARG region that surrounds bla NDM . An additional gene cassette bracketed by two IS 26 elements and carrying bla TEM‐1 was found downstream of rmtB (a gene expressing an aminoglycoside resistance determinant) …”