Identification of a PVL-negative SCCmec-IVa sub-lineage of the methicillin-resistant Staphylococcus aureus CC80 sub-lineage

Background: Community-acquired MRSA (CA-MRSA) isolates belonging to clonal complex 80 (CC80) are known as the European CA-MRSA clone. The prevailing CC80 CA-MRSA clone carries a type IVc staphylococcal cassette chromosome mec (SCCmec) and expresses the Panton-Valentin leukocidin (PVL) encoded by lukS/F-PV. However, recently, a significant increase in the appearance of PVL-negative CC80 MRSA has been observed in Denmark. Objectives: The aim of this study was to examine the genetics and epidemiology of PVL-negative CC80 MRSA isolates and compare them to the dominant European CA-MRSA clone in order to explore the evolution of PVL-negative CC80 MRSA. Methods: Phylogenetic analysis of the CC80 S. aureus lineage was conducted from whole-genome sequences of 217 isolates (23 MSSA and 194 MRSA). All isolates were further characterized in regard to resistance and selected virulence factors. Results: The phylogenetic analysis revealed the existence of three distinct clades of the CC80 lineage: i) a MSSA clade encompassing Sub-Saharan African isolates, ii) a derived clade encompassing MRSA SCCmec-IVc isolates, and iii) a third, and novel, basal clade encompassing MRSA SCCmec-IVa isolates. In addition to carrying another SCCmec subtype, these latter isolates are distinguished from the prevailing European CA-MRSA clone by being PVL-negative and susceptible to fusidic acid and kanamycin/amikacin. Also, geospatial mapping points to a distinct geographic origin of this newly discovered PVL-negative MRSA-SCCmec-IVa sub-lineage. Conclusions: This study shows that the CC80 CA-MRSA lineage is more diverse than previously assumed and provides new insight into the general emergence and global spread of CA-MRSA.