Global dissemination of optrA-mediated linezolid resistance in enterococci

Acquired resistance to last-line linezolid has emerged in Enterococcus spp. and can be conferred by the optrA gene. Here, we study the global genomic context of optrA in E. faecalis and E. faecium, to understand its dissemination pattern.

We identified 565 enterococcal genomes from NCBI and 86 optrA-containing enterococcal plasmids from the plasmid database, PLSDB. We characterized the plasmid replication and antimicrobial resistance genes of optrA-containing plasmids and the plasmid pangenome. To identify prevalent optrA genetic contexts, we mapped the genomes against PLSDB plasmid and transposon Tn6674 (prevalent in E. faecalis) sequences using minimap2.

A greater proportion of E. faecium (47.3%: n = 70/149) carried the optrA gene on plasmids than E. faecalis (28.9%: n = 120/416). In E. faecalis, the major optrA contexts were represented either by a Tn6674 transposon (28.0%) or a plasmid-associated MDR fexA-optrA-erm(A) genetic unit (32.9%), and were associated with distinct E. faecalis phylogroups. In E. faecium, the dominant optrA contexts were the optrA-erm(A)/(B) genetic unit (24.2%), the fexA-optrA-erm(A) unit (16.8%), and the Tn6261 transposon (14.1%). We observed that in some E. faecalis and E. faecium plasmids, the fexA-optrA-erm(A) unit was flanked by IS1216E elements on both sides, suggesting the mobilization of this MDR gene cassette by IS1216E-like elements into diverse plasmid backgrounds.

This is the first study to investigate the genomic context of optrA in a phylogeographically diverse enterococcal genome collection. We demonstrated that mobile genetic elements play a key role in the global expansion of optrA and highlighted the underlying public health concern imposed by plasmids in drug-resistant enterococcal dissemination.