Characterization of Enterococcus faecium Based on Multi-Omics Approaches: Genomic, Transcriptomic, and Phenotypic Analyses

Animal-derived <i>E. faecium</i> poses a public health risk due to its capacity to acquire antimicrobial resistance (AMR) and virulence genes. However, the pathogenicity and cross-host transmission potential of strains originating from unique environments, such as the Qinghai-Tibet Plateau, remain poorly understood. In this study, a strain of <i>E. faecium</i> was isolated from yak feces. We constructed a phylogenetic tree and identified AMR and virulence genes via whole-genome sequencing. Antimicrobial susceptibility testing was performed to determine its resistance phenotype. An in vivo mouse infection model was established to assess pathogenicity, and transcriptomic analysis was utilized to investigate the host's molecular response mechanisms in infected intestinal tissue. The results indicated that this yak-derived strain is closely related to human clinical isolates, suggesting a risk of cross-host transmission. The strain harbored the AMR genes <i>AAC(6')-Ii</i>, <i>msrC</i>, and <i>eatAv</i> and exhibited resistance to penicillin, kanamycin, erythromycin, and clindamycin. The strain harbored key virulence genes, such as <i>bopD</i>, <i>Acm</i>, and <i>ClpP</i>. Infection with this strain caused characteristic inflammatory damage in mouse intestinal tissue, as revealed by histopathological examination, including epithelial necrosis, vascular congestion, and inflammatory cell infiltration. Transcriptomics further delineated a complete "Recognition-Response-Damage" signaling axis: pathogen recognition through Toll-like receptors and NOD-like receptors activates the NF-κB and MAPK signaling pathways. This activation is accompanied by significant upregulation of various inflammatory factors and recruits immune cells via chemokine signaling, ultimately leading to tissue damage. Our findings provide insights into the pathogenic pathway of this strain from genetic determinants to phenotypic manifestations, providing a theoretical foundation for assessing the public health risk posed by animal-derived <i>E. faecium</i> and for developing targeted intervention strategies.