Genomic insights into the global dissemination of linezolid resistance genes in Enterococcus faecium

BackgroundTransferable linezolid resistance determinants in Enterococcus faecium, particularly optrA, poxtA, and cfr, have raised increasing global concern due to their potential dissemination across clinical, animal, food, and environmental reservoirs. However, their population distribution, genomic contexts, and associated virulence backgrounds remain incompletely understood.MethodsWe performed a large-scale genomic analysis of 2,235 publicly available E. faecium genomes to investigate the distribution, sequence types (STs), virulence factors (VFs), and genomic contexts of transferable linezolid resistance genes. Phylogenetic analysis and comparative examination of gene flanking regions were conducted to explore the mechanisms underlying resistance gene dissemination.ResultsA total of 243 genomes (10.9%) carried at least one linezolid resistance gene. poxtA (8.1%) and optrA (6.9%) were more frequently detected than cfr (2.2%). Multiple resistance determinants were simultaneously observed within individual isolates, with optrA + poxtA representing the most frequent gene combination. These resistance genes were distributed across 90 distinct STs, indicating substantial population diversity. Comparative phylogenetic and genomic context analyses revealed significant genetic diversity and a lack of strict phylogenetic clustering, suggesting that horizontal gene transfer mediated by mobile genetic elements plays a major role in the dissemination of these determinants. VF analysis identified 44 virulence genes, with several adherence-associated genes highly conserved across isolates. Notably, certain adherence-related VFs were enriched in isolates harboring multiple resistance genes.ConclusionTogether, these findings highlight the widespread dissemination of optrA-, poxtA-, and cfr-mediated linezolid resistance in diverse E. faecium genomic backgrounds and underscore the important role of horizontal gene transfer in their spread. Continuous genomic surveillance integrating resistance and virulence analyses will be essential for understanding and controlling the global transmission of linezolid-resistant E. faecium.