Cited by 75Antibiotic Resistance in BacteriaAntibiotic Use and ResistanceSalmonella and Campylobacter epidemiology

Silent spread of mobile colistin resistance gene mcr-9.1 on IncHI2 ‘superplasmids’ in clinical carbapenem-resistant Enterobacterales

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Macesic, Nenad, Blakeway, Luke V., Stewart, James D., Hawkey, Jane, Wyres, Kelly L., Judd, Louise M., Wick, Ryan R., Jenney, Adam W. +2 more·2021·Clinical Microbiology and Infection

Abstract

Objectives mcr-9.1 is a newly described mobile colistin resistance gene. We have noted its presence in multiple species of carbapenem-resistant Enterobacterales (CRE) from our institution. We aimed to determine the clinical features, genomic context and phenotypic impact of mcr-9.1 carriage in a series of patients between 2010 and 2019.Methods We identified 32 patients with mcr-9.1-carrying CRE isolates (mCRE) and collected demographic, antimicrobial exposure and infection data. Whole-genome sequencing (including short and long reads) was performed on 32 isolates. We assessed sequence similarity of mcr-9.1-harbouring plasmids, then compared our findings with plasmids for which sequence data were publicly available.Results There was no colistin exposure in patients prior to isolation of mCRE. mcr-9.1 was identified on IncHI2 plasmids across four different bacterial species and was co-located with bla IMP-4 in 23/30 plasmids studied. mCRE isolates did not demonstrate phenotypic colistin resistance, either at baseline or following sublethal colistin exposure, thus showing that mcr-9.1 alone is not sufficient for resistance. Publicly available sequence data indicated the presence of carbapenemase genes in 236/619 mcr-9.1-carrying genomes (38%). IncHI2 plasmids carrying mcr-9.1 and carbapenemase genes were detected in genomes from North America, Europe, North Africa, Asia and Oceania.Conclusions Spread of mcr-9.1 in CRE from our institution was driven by IncHI2 'superplasmids', so termed because of their large size and their prolific carriage of resistance determinants. These were also detected in global CRE genomes. Phenotypic colistin resistance was not detected in our isolates but remains to be determined from global mCRE.

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Crossref · 10.1016/j.cmi.2021.04.020

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Authors
Macesic, N., Blakeway, L. V., Stewart, J. D., Hawkey, J., Wyres, K. L., Judd, L. M., Wick, R. R., Jenney, A. W., Holt, K. E., & Peleg, A. Y.
Affiliations
  • The Alfred Hospital (AU)
  • Cairns Hospital (AU)
  • Monash University (AU)
  • London School of Hygiene & Tropical Medicine (GB)
Venue
Clinical Microbiology and Infection
Publisher
Elsevier BV
Published
2021-12
Volume
27
Issue
12
Pages
1856.e7-1856.e13
ISSN
1198-743X (ISSN-L)
OpenAlex
W3157990845
Cited by
75
References
40
Citations by year
2026: 17 · 2025: 16 · 2024: 8 · 2023: 12 · 2022: 18 · 2021: 4
FWCI
3.32
Type
journal article
Language
en
Open access
Locations
  • Clinical Microbiology and Infection (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • GlaxoSmithKline
  • Meso Scale Diagnostics
  • National Health and Medical Research Council (APP1117940, APP1176324)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Antibiotic Resistance in Bacteria
  • Life Sciences › Immunology and Microbiology › Applied Microbiology and Biotechnology › Antibiotic Use and Resistance
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Salmonella and Campylobacter epidemiology
Keywords
colistin resistance, IncHI2 plasmid, carbapenem-resistant Enterobacteriaceae, carbapenemase genes, mobile resistance genes, antimicrobial resistance dissemination, clinical isolates
MeSH terms
Anti-Bacterial Agents, Colistin, Enterobacteriaceae, Genes, Bacterial, Microbial Sensitivity Tests, Plasmids, Carbapenems, Drug Resistance, Bacterial

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