Nenad Macesic1, Luke V Blakeway2, James D Stewart3, Jane Hawkey4, Kelly L Wyres4, Louise M Judd4, Ryan R Wick4, Adam W Jenney5, Kathryn E Holt6, Anton Y Peleg7. 1. Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia; Department of Infectious Diseases, Alfred Health, Melbourne, Australia. Electronic address: nenad.macesic@monash.edu. 2. Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia; Department of Infectious Diseases, Alfred Health, Melbourne, Australia. 3. Department of Infectious Diseases, Cairns Hospital, Cairns, Australia. 4. Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia. 5. Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia; Department of Infectious Diseases, Alfred Health, Melbourne, Australia; Microbiology Unit, Alfred Pathology Service, Alfred Health, Melbourne, Australia. 6. Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia; The London School of Hygiene and Tropical Medicine, London, United Kingdom. 7. Department of Infectious Diseases, Central Clinical School, Monash University, Melbourne, Australia; Department of Infectious Diseases, Alfred Health, Melbourne, Australia; Infection and Immunity Program, Monash Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton, Australia.
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 blaIMP-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.
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 blaIMP-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.
Authors: Javier E Cañada-García; Zaira Moure; Pedro J Sola-Campoy; Mercedes Delgado-Valverde; María E Cano; Desirèe Gijón; Mónica González; Irene Gracia-Ahufinger; Nieves Larrosa; Xavier Mulet; Cristina Pitart; Alba Rivera; Germán Bou; Jorge Calvo; Rafael Cantón; Juan José González-López; Luis Martínez-Martínez; Ferran Navarro; Antonio Oliver; Zaira R Palacios-Baena; Álvaro Pascual; Guillermo Ruiz-Carrascoso; Jordi Vila; Belén Aracil; María Pérez-Vázquez; Jesús Oteo-Iglesias Journal: Front Microbiol Date: 2022-06-30 Impact factor: 6.064
Authors: Kelly L Wyres; Jane Hawkey; James Stewart; Louise M Judd; Adam Jenney; Kathryn E Holt Journal: BMC Infect Dis Date: 2022-08-24 Impact factor: 3.667