Emergence of ST3390: A novel apigmented MRSA clone from the CC5 Lineage.

Background: One of the most successful and widely-distributed hospital-associated lineages of MRSA is clonal complex 5 (CC5). These strains are known for widespread antibiotic resistance, but less severe disease than CA-MRSA counterparts. Recently, CC5 descendant lineages have appeared globally with hypervirulent properties. Herein we identify and characterize a rare and novel CC5 MRSA sequence type, ST3390.

Methods: We used whole genome sequencing, alongside phenotypic characterizations, genetic complementation, blood viability- and neutrophil-killing assays, and a murine model of sepsis to study the pathogenic capabilities of ST3390 strains.

Results: To date, there have only been 65 recorded instances of infection caused by ST3390 globally, with 36 of those occurring in Tampa (TPA-ST3390). Genomic analysis of strains identified numerous spa-types, with a t010 cluster found only in our strains. Exploration of AMR genes detected the presence of unique hybrid SCCmec types, with ∼90% of Tampa strains possessing components of SCCmecIa, SCCmecIIa and/or SCCmecVIII. Phenotypically, all ST3390 strains lack the staphyloxanthin pigment, which is mediated by a conserved 6aa in frame deletion within the staphyloxanthin biosynthesis protein CrtN. TPA-ST3390 strains display high levels of cytotoxicity towards human neutrophils compared to other CC5 lineages, and are also virulent in animal models of infection.

Conclusions: This is the first study to characterize the pathogenicity and genomic architecture of the rare MRSA lineage ST3390. Our work provides a deeper understanding of the clonal expansion of CC5, and the wider diversification of S. aureus isolates within patient populations.