Transmission dynamics and molecular characterization of methicillin-resistant <i>S. epidermidis</i> among men who have sex with men in Guangzhou, China

Methicillin-resistant <i>Staphylococcus epidermidis</i> (MRSE) is a major opportunistic pathogen associated with high morbidity and mortality. However, its transmission dynamics and molecular characteristics in high-risk populations such as men who have sex with men (MSM) remain poorly understood. A community-based cross-sectional study was performed to recruit 510 MSM, providing nasal swabs for MRSE analysis. All MRSE isolates were characterized using antimicrobial susceptibility testing, whole-genome sequencing, and phylogenetic analysis, so as to reveal genomic diversity and transmission clusters. Among 510 MSM participants, the nasal colonization rates of <i>S. epidermidis</i> and MRSE were 82.75% and 44.12%, respectively. Genomic analyses of 190 MRSE isolates identified 20.53% as homologous, forming 12 transmission clusters and 40 transmission routes. In addition, homologous isolates exhibited distinct resistance and virulence profiles (<i>tet(K</i>), <i>ANT(4')-Ib, esaA</i>, <i>esaB</i>, <i>icaA</i>, <i>icaB</i>, <i>icaC</i>, <i>icaR</i>, <i>essA</i>, <i>essB</i>, <i>essC</i>, and <i>esxA</i>; all <i>P</i> < 0.05) and genotypes (ST130, ST20, ST35, and ST57; all <i>P</i> < 0.05). The final Random Forest model achieved an accuracy of 81.58% in predicting homologous transmission risk. These findings highlight the high carriage risk and complex dynamics of MRSE transmission in this high-risk population, emphasizing the need for targeted surveillance and infection control strategies.IMPORTANCEThis study uncovers high nasal methicillin-resistant <i>Staphylococcus epidermidis</i> (MRSE) colonization (44.12%) and complex transmission dynamics among men who have sex with men (MSM), a key reservoir for multidrug-resistant <i>S. epidermidis</i>. Whole-genome analysis identified 12 transmission clusters and 40 transmission routes, with homologous isolates enriched in <i>tet(K</i>) and <i>ANT(4')-Ib</i> resistance genes but lacking biofilm-associated <i>ica</i> genes. A Random Forest model achieved a classification accuracy of 81.58% for predicting transmission risk. These findings highlight MSM as critical hubs for community MRSE spread and provide actionable targets for surveillance, guiding effective infection control strategies to curb antimicrobial resistance.