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

Abstract

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 (SCCmec) types, multi-locus sequence types (MLST) and staphylococcal protein A (spa) types. Whole genome sequence data of ST772-SCCmec V (n=32) isolates were generated and analysed along with the publically available ST772-SCCmec 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-SCCmec V was emerged on the Indian subcontinent in 1960s. The acquisition of integrated resistance plasmid (IRP) in the ST772-SCCmec V lineage during 1990s, fixation of SCCmec 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 (blaZ), aminoglycosides (aphA3-sat-aadE), macrolide (mphC), macrolide-lincosamide-streptogramin B (msrA) and bacitracin (bacA, bacB). Conclusions: The Panton Valentine Leukocidin (PVL) positive ST772 and ST22 MRSA lineages are observed in the hospital settings. ST772-SCCmec 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.