Clonal outbreak of mecC-methicillin-resistant Staphylococcus aureus carriage linked to phage-mediated acquisition of immune evasion cluster genes.

Abstract

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 contextualized the outbreak isolates within the global mecC-MRSA population using whole-genome sequencing.

Methods: Seven mecC-MRSA isolates from screening samples from patients hospitalized 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 multilocus sequence typing was performed to assess clonality. These were compared with 571 publicly available mecC-MRSA genome assemblies retrieved from National Center for Biotechnology Information. Immune evasion cluster (IEC) genes were sought. Associated prophage regions were characterized using PHASTEST.

Results: All seven outbreak isolates belonged to ST599, shared the same complex type (CT47051), and differed by a maximum of four core-genome multilocus sequence typing allelic differences, confirming clonal transmission. Six of seven were detected within 48 hours of admission; all patients resided in a semirural 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, whereas 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.