Silent spread of mobile colistin resistance gene mcr-9.1 on IncHI2 ‘superplasmids’ in clinical carbapenem-resistant Enterobacterales
Open accessAbstract
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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The mcr-9.1 gene was first identified in Salmonella enterica in 2019, where it conferred phenotypic resistance to colistin, and has since been associated with Enterobacter and Klebsiella species, often on mobile IncHI2 plasmids.
“The mcr-9.1 gene was first identified in Salmonella enterica in 201942, where it conferred phenotypic resistance to colistin, and has since been associated with Enterobacter and Klebsiella species, often on mobile IncHI2 plasmids43.”
From Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants. (2025) · cites this paper as [43]
The finding of mcr-9.1 aligns with previous retrospective studies that identified mcr-9 prior to its first official report, highlighting the value of metagenomics in antimicrobial resistance surveillance.
“Our finding aligns with previous retrospective studies43,44 that identified mcr-9 prior to its first official report, highlighting the value of metagenomics in AMR surveillance.”
From Impact of early life antibiotic and probiotic treatment on gut microbiome and resistome of very-low-birth-weight preterm infants. (2025) · cites this paper as [43]
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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)
- ORCID
- 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
- bronze
- doi.org
- Licence
- 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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