Clonal outbreak of mecC-MRSA carriage linked to phage-mediated acquisition of immune evasion cluster genes.

OBJECTIVES

mecC-carrying methicillin-resistant Staphylococcus aureus (mecC-MRSA) are predominantly animal-associated pathogens that rarely cause human infections and have not been linked to hospital outbreaks. We investigated a suspected cluster of mecC-MRSA in a Belgian hospital and contextualised the outbreak isolates within the global mecC-MRSA population using whole-genome sequencing.

METHODS

Seven mecC-MRSA isolates from screening samples from patients hospitalised in a single unit between September 2024 and January 2025 underwent whole genome sequencing alongside 16 unrelated human and 3 bovine mecC-MRSA from Belgium. Core-genome MLST (cgMLST) was performed to assess clonality. These were compared with 571 publicly available mecC-MRSA genome assemblies from NCBI. Immune evasion cluster (IEC) genes were sought. Associated prophage regions were characterised using PHASTEST.

RESULTS

All seven outbreak isolates belonged to ST599, shared the same complex type (CT47051), and differed by a maximum of 4 cgMLST allelic differences, confirming clonal transmission. Six of seven were detected within 48 hours of admission; all patients resided in a semi-rural area within a 23 km radius. The outbreak isolates harboured IEC genes sak and sea on a ΦSa3-like prophage, a novel IEC variant lacking scn and chp, while an unrelated CC599 Belgian human isolate harboured sak and scn. Among publicly available mecC-MRSA assemblies, CC599 represented only 16 isolates (2.8%), and IEC genes were carried only by 6 isolates (0.9%)- none within CC599. The outbreak cluster was most closely related to an unrelated historical Belgian bovine ST599 isolate (75 allelic differences).

CONCLUSIONS

This first documented clonal mecC-MRSA outbreak was caused by a rare ST599 clone that acquired IEC genes through phage-mediated horizontal transfer, a feature associated with human adaptation and enhanced transmissibility in other S. aureus lineages. These findings highlight the need for mecC-capable diagnostic assays and One Health genomic surveillance to detect emerging human-adaptive mecC-MRSA clones.