Plasmid analysis of NDM metallo-β-lactamase-producing Enterobacterales isolated in Vietnam

PLoS One. 2021 Jul 28;16(7):e0231119. doi: 10.1371/journal.pone.0231119. eCollection 2021.

Abstract

Carbapenem-resistant Enterobacterales (CRE) represent a serious threat to public health due to the lack of treatment and high mortality. The rate of antimicrobial resistance of Enterobacterales isolates to major antimicrobials, including carbapenems, is much higher in Vietnam than in Western countries, but the reasons remain unknown due to the lack of genomic epidemiology research. A previous study suggested that carbapenem resistance genes, such as the carbapenemase gene blaNDM, spread via plasmids among Enterobacterales in Vietnam. In this study, we characterized blaNDM-carrying plasmids in Enterobacterales isolated in Vietnam, and identified several possible cases of horizontal transfer of plasmids both within and among species of bacteria. Twenty-five carbapenem-nonsusceptible isolates from a medical institution in Hanoi were sequenced on Illumina short-read sequencers, and 13 blaNDM-positive isolates, including isolates of Klebsiella pneumoniae, Escherichia coli, Citrobacter freundii, Morganella morganii, and Proteus mirabilis, were further sequenced on an Oxford Nanopore Technologies long-read sequencer to obtain complete plasmid sequences. Almost identical 73 kb IncFII(pSE11)::IncN hybrid plasmids carrying blaNDM-1 were found in a P. mirabilis isolate and an M. morganii isolate. A 112 kb IncFII(pRSB107)::IncN hybrid plasmid carrying blaNDM-1 in an E. coli isolate had partially identical sequences with a 39 kb IncR plasmid carrying blaNDM-1 and an 88 kb IncFII(pHN7A8)::IncN hybrid plasmid in a C. freundii isolate. 148-149 kb IncFIA(Hl1)::IncA/C2 plasmids and 75-76 kb IncFII(Yp) plasmids, both carrying blaNDM-1 were shared among three sequence type 11 (ST11) isolates and three ST395 isolates of K. pneumoniae, respectively. Most of the plasmids co-carried genes conferring resistance to clinically relevant antimicrobials, including third-generation cephalosporins, aminoglycosides, and fluoroquinolones, in addition to blaNDM-1. These results provide insight into the genetic basis of CRE in Vietnam, and could help control nosocomial infections.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Carbapenems / pharmacology
  • Enterobacteriaceae / drug effects
  • Enterobacteriaceae / enzymology
  • Enterobacteriaceae / genetics
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / epidemiology
  • Enterobacteriaceae Infections / microbiology
  • Escherichia coli / drug effects
  • Escherichia coli / genetics
  • Escherichia coli / isolation & purification
  • Humans
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / isolation & purification
  • Microbial Sensitivity Tests
  • Plasmids* / genetics
  • Vietnam
  • beta-Lactamases* / genetics

Substances

  • beta-Lactamases
  • beta-lactamase NDM-1
  • Anti-Bacterial Agents
  • Carbapenems

Grants and funding

This study was supported by Nagasaki University (2019-Ippan-20 to MS), the Japan Society for the Promotion of Science (20K07509 to MS and 21K15440 to AH), and the Japan Agency for Medical Research and Development (JP20fk0108061, JP18fm0108003, JP19fm0108006, and JP21fk0108604 to KS) (JP21fk0108093, JP21fk0108139, JP21fk0108133, JP21wm0325003, JP21wm0325022, JP21wm0225004, and JP21wm0225008 to MS) (JP17fm0108023 to TI).