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.