Role of mobile genetic elements in linezolid-resistant Enterococci: a global and Australian perspective
Jia Qi Beh 2, Benjamin P. Howden 1,2,3, Christopher H. Connor 2* and Jessica R Webb 2*
1 Microbiological Diagnostic Unit Public Health Laboratory, Department of Microbiology and Immunology at the Peter Doherty Institute for Infection & Immunity, The University of Melbourne, Melbourne, Victoria, Australia.
2 Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
3 Centre for Pathogen Genomics, University of Melbourne, Melbourne, Victoria, Australia.
Plasmids are mobile genetic elements capable of horizontal transmission of antimicrobial resistance genes in bacteria. Linezolid is a last resort antibiotic to treat multidrug-resistant Enterococcus spp. Resistance can be acquired through transferable genes carried on plasmids. Notably, the linezolid resistance gene optrA represents a One Health concern and has been described from both clinical human and livestock screening, potentially exacerbated by florfenicol use in animal husbandry. Despite its widespread occurrence, there is no systematic study on the global vector diversity and pattern distribution for optrA. Here, we gathered (i) a comprehensive global dataset of 2,047 Enterococcus faecalis and 7,828 Enterococcusfaecium genomes from NCBI representing diverse geographical and ecological scales, and (ii) all known optrA plasmid and transposon vectors from PLSDB and literature searches, to understand the genomic and geographical signatures of optrA vectors. From the global dataset, we observed a higher optrA carriage rate in E. faecalis (4.7%) than E. faecium (0.65%). Using pairwise alignment detection, we showed that distinct optrA vectors and protein variants were circulating in the two enterococcal species. Notably in E. faecalis, two dominant vectors – the 12.9-kb Tn6674 transposon and a 8.3-kb plasmid context, were responsible for a significant portion (48.8%) of optrA transmission. Both vectors were widespread across different continents and persisted since 2015 but were prevalent in distinct phylogroups. In E. faecium, we found no dominant optrA vector but identified a putative linear plasmid family that was present across different phylogroups. Genomic comparison of Australian to global optrA enterococci suggested an influx of international strains which further multiplied via clonal expansion. Our findings demonstrate that diverse mobile genetic elements serve as important vehicles for global dissemination of critical resistance gene optrA in enterococci across geographical and ecological scales and underscore the significance of optrA enterococci as an ongoing concern for One Health practitioners.