LARGE RETROSPECTIVE WGS STUDY DESCRIBES GENOMIC EPIDEMIOLOGY OF S. AUREUS IN INDIA AND REVEALS TWO NOVEL MULTI-DRUG RESISTANT SUB-LINEAGES OF S. AUREUS CLONAL COMPLEX 22

Abstract

Intro: S. aureus is a major pathogen in India, causing nosocomial infections, but little is known about its molecular epidemiology and mechanisms of resistance in hospital settings. Here, we use WGS to characterize 508 S. aureus clinical isolates collected across India and analyze them in a global context. Methods: Whole-genome sequencing was performed on 508 clinical isolates of S. aureus collected from 17 sentinel sites across India between 2014 and 2019 with the Illumina platform. AMR genotypes were predicted using Staphopia. Isolates carrying novel SCCmec cassettes were further characterized using long-read sequencing. A temporal analysis of clonal complex (CC) 22 global isolates from 14 different studies was performed using BactDating. Findings: Sequencing results confirmed 478 isolates as S. aureus. ST22, ST772 & ST239 were the major clones identified. An in-depth analysis of the 175 CC22 Indian isolates identifies two novel ST22 MRSA clones, PVL+ and one harboring the tsst-1 gene. Temporal analysis showed that these two ST22 clusters shared a common ancestor in the 1980s and they became widespread after the year 2000 in India. Analyzing these in a global context, we found evidence of transmission of the two Indian clones to other parts of the world. Discussion: Temporal analysis shows that two ST22 clusters originated around 2010 in India and we found evidence of transmission of the two Indian clones in other parts of the world. The novel SCCmec types identified in our study are characterized using long reads to understand their genetic structure. Conclusion: Our study describes a large retrospective S. Aureus sampled from India. By comparing the Indian isolates globally, we show the evidence of the international transmission of ST22 Indian isolates. Even though the two of the major dominant clones (ST772 and ST239) using WGS have been reported, this is the first study that describes the third dominant clone (ST22) in India.