Global distribution and genomic characteristics of linezolid resistance gene-positive Enterococcus faecium among humans, animals, and the environment.

BACKGROUND: Over the past decade, considerable attention has been directed toward the plasmid-mediated dissemination of linezolid resistance determinants among Enterococcus faecium (E. faecium). Despite extensive epidemiological research, a systematic global genomic analysis of linezolid resistance gene-positive E. faecium (LRGPEfm) is lacking. METHODS: This study conducted a comprehensive genomic analysis of 832 LRGPEfm genomes, with the aim of investigating their antibiotic resistance genes (ARGs), virulence factor genes (VFGs), population structure, and transmission pathways. RESULTS: The greatest proportion of LRGPEfm originated from China (32.57%), with Germany following at 11.54%. In relation to host origin, humans represented the dominant category (48.08%), followed by pigs (10.58%). LRGPEfm additionally functions as a repository for ARGs, with a total of 47 ARGs identified. Isolates from China and pigs harbored the highest ARG numbers. Furthermore, 35 VFGs were identified, with isolates from hospital environments and Germany harboring the highest VFG numbers. A total of 211 sequence types were delineated through multilocus sequence typing (MLST) analysis, with ST80 being the most common. Minimal SNP differences detected in LRGPEfm originating from various countries and host sources suggest cross-border and cross-species clonal dissemination. Pan-genome-wide association studies (pan-GWAS) demonstrated that the accessory genome of LRGPEfm varies significantly by geography and host, showing a marked enrichment of genes associated with metabolic enzymes, mobile genetic elements (MGEs), and ARGs. Among the genetic contexts of linezolid resistance genes, IS1216E was the predominant carrier. CONCLUSION: LRGPEfm poses a substantial public health threat, and sustained, comprehensive surveillance is essential.