Identification of a PVL-negative SCCmec-IVa sub-lineage of the methicillin-resistant Staphylococcus aureus CC80 lineage: Understanding the clonal origin of CA-MRSA

OBJECTIVES: Community-acquired MRSA (CA-MRSA) isolates belonging to clonal complex 80 (CC80) are recognized as the European CA-MRSA. The prevailing European CA-MRSA clone carries a type IVc staphylococcal cassette chromosome mec (SCCmec) and expresses Panton-Valentine leukocidin (PVL). Recently, a significant increase of PVL-negative CC80 MRSA has been observed in Denmark. The aim of this study was to examine the genetics and the epidemiology of these, and to compare them to the European CA-MRSA clone in order to understand the emergence 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) from 22 countries. All isolates were further genetically characterized in regard to resistance determinants and PVL carriage, and epidemiological data was obtained for selected isolates.

RESULTS: The phylogenetic analysis revealed the existence of three distinct clades of the CC80 lineage: i) an MSSA clade encompassing Sub-Saharan African isolates (n=13); ii) a derived clade encompassing the European CA-MRSA SCCmec-IVc clone (n=185); and iii) a novel and genetically distinct clade encompassing MRSA SCCmec-IVa isolates (n=19). All isolates in the novel clade were PVL negative, but carried remnant parts (8 -12 kb) of the PVL-encoding prophage ΦSa2, and were susceptible to fusidic acid and kanamycin/amikacin. Geospatial mapping could link these isolates to regions in the Middle East, Asia and South Pacific.

CONCLUSIONS: This study reports the emergence of a novel CC80 CA-MRSA sub-lineage, showing that the CC80 lineage is more diverse than previously assumed.