Evolution and Global Transmission of a Multidrug-Resistant, Community-Associated Methicillin-Resistant Staphylococcus aureus Lineage from the Indian Subcontinent.

Eike J Steinig,D Ashley Robinson,Maho Yokoyama,Elizabeth Dickson,David C Coleman,Stefan Weber,Stephen D Bentley,Helen Heffernan,Anna C Shore,Geoffrey W Coombs,Birgit Strommenger,Maisem Laabei,Henrik Westh,Peter Slickers,Sharon J Peacock,Annalisa Pantosti,Leila Skakni,Franziska Layer,Nobumichi Kobayashi,Hege Vangstein Aamot,Steven Y C Tong,Andreas Petersen,Matthew V N O’Sullivan,Ralf Ehricht,Margaret Ip,Richard V Goering,Angela Kearns,Patiyan Andersson,Julian Parkhill,Stefan Monecke,Ruth C Massey,Matthew T G Holden ,Deborah A Williamson ,Derek S Sarovich ,Simon R Harris ,Hermı́nia De Lencastre ,Sebastián Duchêne ,Gráinne I Brennan

doi:10.1128/mbio.01105-19

Abstract

The evolution and global transmission of antimicrobial resistance have been well documented for Gram-negative bacteria and health care-associated epidemic pathogens, often emerging from regions with heavy antimicrobial use. However, the degree to which similar processes occur with Gram-positive bacteria in the community setting is less well understood. In this study, we traced the recent origins and global spread of a multidrug-resistant, community-associated Staphylococcus aureus lineage from the Indian subcontinent, the Bengal Bay clone (ST772). We generated whole-genome sequence data of 340 isolates from 14 countries, including the first isolates from Bangladesh and India, to reconstruct the evolutionary history and genomic epidemiology of the lineage. Our data show that the clone emerged on the Indian subcontinent in the early 1960s and disseminated rapidly in the 1990s. Short-term outbreaks in community and health care settings occurred following intercontinental transmission, typically associated with travel and family contacts on the subcontinent, but ongoing endemic transmission was uncommon. Acquisition of a multidrug resistance integrated plasmid was instrumental in the emergence of a single dominant and globally disseminated clade in the early 1990s. Phenotypic data on biofilm, growth, and toxicity point to antimicrobial resistance as the driving force in the evolution of ST772. The Bengal Bay clone therefore combines the multidrug resistance of traditional health care-associated clones with the epidemiological transmission of community-associated methicillin-resistant S. aureus (MRSA). Our study demonstrates the importance of whole-genome sequencing for tracking the evolution of emerging and resistant pathogens. It provides a critical framework for ongoing surveillance of the clone on the Indian subcontinent and elsewhere.IMPORTANCE The Bengal Bay clone (ST772) is a community-associated and multidrug-resistant Staphylococcus aureus lineage first isolated from Bangladesh and India in 2004. In this study, we showed that the Bengal Bay clone emerged from a virulent progenitor circulating on the Indian subcontinent. Its subsequent global transmission was associated with travel or family contact in the region. ST772 progressively acquired specific resistance elements at limited cost to its fitness and continues to be exported globally, resulting in small-scale community and health care outbreaks. The Bengal Bay clone therefore combines the virulence potential and epidemiology of community-associated clones with the multidrug resistance of health care-associated S. aureus lineages. This study demonstrates the importance of whole-genome sequencing for the surveillance of highly antibiotic-resistant pathogens, which may emerge in the community setting of regions with poor antibiotic stewardship and rapidly spread into hospitals and communities across the world.

Highlights

Methicillin-resistant Staphylococcus aureus (MRSA) is a major human pathogen with a propensity to develop antibiotic resistance, complicating treatment and allowing persistence in environments where there is antibiotic selection pressure
In this study, we used whole-genome sequencing in combination with epidemiological and phenotypic data to investigate the drivers behind the emergence and spread of a multidrug-resistant community-associated methicillin-resistant S. aureus (MRSA) lineage from the Indian subcontinent
Our data suggest that the Bengal Bay clone has acquired the multidrug resistance phenotype of traditional health care-associated MRSA but retains the epidemiological characteristics of community-associated MRSA

Summary

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) is a major human pathogen with a propensity to develop antibiotic resistance, complicating treatment and allowing persistence in environments where there is antibiotic selection pressure. Over the last few years, several population genomic studies have started to unravel the evolutionary history of community-associated S. aureus lineages emerging in specific regions of the world The prototype of these clones is the diverse USA300 lineage (sequence type 8 [ST8]), forming distinct genetic lineages in North America and South America [4, 5], including distinct clades in Europe and Africa [6]. On the Australian continent, ST93 emerged in indigenous communities of Western Australia and the Northern Territory and spread to the eastern seaboard and sporadically overseas, while forming a clade associated with Pacific Islander and Maori populations in New Zealand [9] This diversity of regional evolutionary histories is reflected in the various factors that have been suggested to contribute to the emergence and establishment of community-associated clones. Multidrug resistance plasmid appeared to be a driver in the emergence of a dominant clade (ST772-A) in the early 1990s

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