Convergent adaptation in the dominant global hospital clone ST239 of methicillin-resistant Staphylococcus aureus

MBio
Sarah L BainesBenjamin P Howden

Abstract

Infections caused by highly successful clones of hospital-associated methicillin-resistant Staphylococcus aureus (HA-MRSA) are a major public health burden. The globally dominant sequence type 239 (ST239) HA-MRSA clone has persisted in the health care setting for decades, but the basis of its success has not been identified. Taking a collection of 123 ST239 isolates spanning 32 years, we have used population-based functional genomics to investigate the evolution of this highly persistent and successful clone. Phylogenetic reconstruction and population modeling uncovered a previously unrecognized distinct clade of ST239 that was introduced into Australia from Asia and has perpetuated the epidemic in this region. Functional analysis demonstrated attenuated virulence and enhanced resistance to last-line antimicrobials, the result of two different phenomena, adaptive evolution within the original Australian ST239 clade and the introduction of a new clade displaying shifts in both phenotypes. The genetic diversity between the clades allowed us to employ genome-wide association testing and identify mutations in other essential regulatory systems, including walKR, that significantly associate with and may explain these key phenotypes....Continue Reading

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Citations

Apr 9, 2016·Current Opinion in Microbiology·B Jesse Shapiro
Feb 18, 2016·Pathogens and Global Health·Stefano GaiarsaDavide Sassera
Sep 15, 2016·Expert Review of Anti-infective Therapy·Stefano G GiulieriBenjamin P Howden
Jan 9, 2020·Microbial Genomics·Stefano G GiulieriDeborah A Williamson
Mar 30, 2017·Microbial Genomics·Sebastian DuchêneEdward C Holmes
Jun 20, 2018·BMC Evolutionary Biology·Sebastian DucheneKathryn E Holt
Feb 6, 2020·Microbial Drug Resistance : MDR : Mechanisms, Epidemiology, and Disease·Ekta Kamble, Karishma Pardesi
Jun 15, 2018·Proceedings. Biological Sciences·Beth GibsonAdam Eyre-Walker
Aug 1, 2018·Infection and Immunity·Deena R AltmanHarm van Bakel
Dec 5, 2016·Nucleic Acids Research·Maria BrbićFran Supek
Mar 16, 2019·Frontiers in Microbiology·Ana Maria Nunes BotelhoAgnes Marie Sá Figueiredo
Mar 22, 2019·BMC Genomics·Anna K SzafrańskaUlrich Nübel
Nov 13, 2020·Microbial Genomics·Sarah L Baines Communicable Diseases Genomics Network Cdgn
Jul 15, 2021·Future Science OA·Yamuna Devi BathavatchalamBalaji Veeraraghavan

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Methods Mentioned

BETA
MDS
genotyping
PCR

Software Mentioned

Dendroscope
BEAST

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