Beyond livestock: the genomic evolution and expansion of MRSA CC398 as a healthcare- and community-associated pathogen (2017–2024)

This study employed whole-genome sequencing to elucidate the genomic diversity and population structure of Staphylococcus aureus clonal complex 398 (CC398) in the Czech Republic over a 7-year period (2017–2024). Among 1,129 MRSA isolates from human patients, 59 CC398 isolates were identified and characterized via core-genome SNP and whole-genome MLST-based phylogenetic reconstruction. The results revealed two phylogenetically and clinically divergent lineages. The ST1232 lineage ( n =27), a human-adapted community-associated (CA) MRSA clone harbouring Panton–Valentine leucocidin and immune evasion cluster (IEC) type B, showed a sharp increase in prevalence after 2022. Phylogenetic analysis suggested multiple independent introductions linked to international travel, primarily to South-East Asia, followed by local expansion within households and among vulnerable populations. In contrast, the ST398 lineage ( n =32) comprised diverse sublineages, including a swine-associated clone (SCC mec Vc) and an equine-associated sublineage (C6-EP5-Leq; SCC mec IVa, IEC type E). ST398 was primarily associated with healthcare-related colonization and long-term persistence in patients with chronic conditions. Our data demonstrate the genomic diversification of CC398 into specialized niches, with the expansion of the virulent ST1232 lineage mirroring the early evolutionary trajectory of successful CA-MRSA clones such as USA300. This study highlights the increasing complexity of CC398 epidemiology, characterized by the simultaneous expansion of livestock-derived sublineages and human-adapted clades, such as ST1232 and underscores the necessity of continuous genomic surveillance within a 'One Health' framework.