Global genomic landscape of Staphylococcus lugdunensis: population structure, antimicrobial resistance, and virulence determinants.

Staphylococcus lugdunensis, a coagulase-negative staphylococcus, has emerged as an opportunistic pathogen causing severe infections. It exhibits genetic diversity, with multiple sequence types, antimicrobial resistance (AMR) genes, and virulence factors. This study aimed to explore its genomic features and clinical implications. Six clinical isolates from Fujian, Beijing, and Wuhan were sequenced using Illumina and Oxford Nanopore platforms, and antimicrobial susceptibility was tested. Other 139 genomes were retrieved from GenBank. Multi-locus sequence typing, phylogenetic and recombination analyses, resistance/virulence gene detection, plasmid replicon identification, and staphylococcal cassette chromosome mec (SCCmec) typing were performed. Among 144 genomes, 19 sequence types (STs) were grouped into five clonal complexes (CCs), with CC3 (notably ST3) and ST27 predominating. Eighteen AMR genes were identified, with blaZ (37.5%), qacD (34.7%), and mecA (14.6%) most frequent. Seven isolates carried ≥5 AMR genes. Virulence genes, including cap8E and esxA, were widely distributed. SCCmec elements were identified in all mecA-positive isolates, with type V predominant in ST3 and type II in ST6. Importantly, 76.2% of SCCmec-positive isolates were infection-associated. Novel plasmids carrying multiple resistance genes were identified in two ST3 isolates. This study reveals extensive genetic diversity, widespread AMRs, and virulence determinants in S. lugdunensis, providing insights for surveillance and therapy.IMPORTANCEThis study highlights a direct public health threat: we found that infection-associated strains of S. lugdunensis frequently carry antimicrobial resistance genes and virulence factors, underscoring their potential to cause severe, hard-to-treat infections. It provides a genetic foundation for surveillance: the identification of predominant high-risk lineages and novel plasmids carrying multiple resistance genes offers crucial molecular targets for future tracking and monitoring of this emerging pathogen. It informs clinical decision-making: understanding the genetic basis of its resistance and virulence is a critical step toward developing more effective strategies for infection control and guiding targeted antibiotic therapy.