High-risk ST772-MRSA lineage in South Asia: potential for global dissemination

Abstract

Background: Methicillin resistant Staphylococcus aureus (MRSA) is a clinically important pathogen with an abundance of virulence factors and multi-drug resistance, that are essential for survival within host. In recent decades, a community-acquired lineage, ST772-MRSA are being frequently reported cause of hospital-onset infections and outbreak. ST772-MRSA is currently circulating in South Asia, Australia and Europe. We hypothesis that the presence of multiple resistance determinants in ST772-MRSA, is the driver for potential adaptation and evolution. Genome-wide association study was conducted to understand the evolutionary events within ST772-MRSA and propensity for dissemination. Methods and materials: Whole genome sequencing was performed for ST772-MRSA (n = 33), isolated from blood culture during 2013-2018. Global collection ST772 S. aureus genome (n = 120) were retrieved from National Center for Biotechnology Information (NCBI) and European Nucleotide Archive (ENA) databases. Core genome alignment and variant calling analysis were carried out using parsnp and snippy pipeline respectively. Divergence and evolution of ST772 S. aureus were estimated using phylogenetic BEAST analysis. Results: ST772-MRSA was emerged in the early 1970s. In this lineage, mecA gene was identified on a short variant (5C2) or composite (5C2&5) SCCmec V element. Among the investigated genome, 90% carried Panton Valentine leukocicidin (PVL) toxin, which is encoded by the prophage Φ-IND772PVL. vSaα, vSaβ and vSaγ pathogenicity islands carrying exotoxins, enterotoxin gene cluster and exfoliative toxin were identified on all ST772-MRSA genome. Mutation in parC (S80Y) and gyrA (S82L), contributed for quinolone resistance in 72% of the genome. A copy of dfrA gene, encoding for trimethoprim resistance was identified on all the core genome. An integrated resistance plasmid (IRP) containing resistant determinants for beta-lactam (blaZ), aminoglycosides (aphA3-sat-aadE), macrolide (msrA, mphC), and bacitracin (bacA, bacB) was found in all MRSA genome. Another landmark event, is the acquisition of IRP, in the early 1990s, resulted in a highly distinct uniform clade comprised of multi-drug resistant variant. Most of this variant mediated intercontinental transmission is typically associated with travel from South Asia. Conclusion: Acquisition of IRP contributed for the emergence of ST772-MRSA lineage, as a multi-drug resistant variant. Genetic changes associated with the adaptation and increasing multi-drug resistance in ST772-MRSA, represents the potential threat for global dissemination.