Origin and evolutionary dynamics of multi-drug resistant and highly virulent community-associated methicillin-resistantStaphylococcus aureusST772-SCCmecV lineage

Background Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) are increasing in prevalence across the world. However, studies on the molecular epidemiology and the genomic investigation of MRSA are limited in India. Objectives To understand the molecular epidemiology of MRSA and to reconstruct the origin and evolution of S. aureus belonged to the sequence type (ST772). Methods A total of 233 non-repetitive MRSA isolates were screened for the presence staphylococcal cassette chromosome (SCC mec ) types, multi-locus sequence types (MLST) and staphylococcal protein A ( spa ) types. Whole genome sequence data of ST772-SCC mec V (n=32) isolates were generated and analysed along with the publically available ST772-SCC mec V (n=273) genome. Results ST772 (27%), ST22 (19%) and ST239 (16%) were found as the predominant STs. Analysis of the core SNPs using Bayesian time scaled phylogenetic analysis showed ST772-SCC mec V was emerged on the Indian subcontinent in 1960s. The acquisition of integrated resistance plasmid (IRP) in the ST772-SCC mec V lineage during 1990s, fixation of SCC mec V (5C2) and the double serine mutations (S84L, S80Y) appears to have played a key role in the successful expansion. The IRP carries the loci for multiple antibiotic resistant genes: beta-lactam ( bla Z), aminoglycosides ( aph A3- sat - aad E), macrolide ( mphC ), macrolide-lincosamide-streptogramin B ( msrA ) and bacitracin ( bac A, bac B). Conclusion The Panton Valentine Leukocidin (PVL) positive ST772 and ST22 MRSA lineages are observed in the hospital settings. ST772-SCC mec V has the multi-drug resistance trait of hospital-associated (HA) MRSA and the epidemiological characteristics of CA-MRSA. The antimicrobial use pattern may have driven the spread and survival of ST772 MRSA in hospitals.