MRSA lineage USA300 isolated from bloodstream infections exhibit altered virulence regulation

Sophie Dyzenhaus, Mitchell J. Sullivan, Bremy Alburquerque, Daiane Boff, Adriana van de Guchte, Marilyn Chung, Yi Fulmer, Richard Copin, Juliana K. Ilmain, Anna O'Keefe, Deena R. Altman, François Xavier Stubbe, Magdalena Podkowik, Amy C. Dupper, Bo Shopsin, Harm van Bakel, Victor J. Torres

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

The epidemic community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) USA300 lineage has recently become a leading cause of hospital-associated bloodstream infections (BSIs). Here, we leveraged this recent introduction into hospitals and the limited genetic variation across USA300 isolates to identify mutations that contribute to its success in a new environment. We found that USA300 BSI isolates exhibit altered virulence regulation. Using comparative genomics to delineate the genes involved in this phenotype, we discovered repeated and independent mutations in the transcriptional regulator sarZ. Mutations in sarZ resulted in increased virulence of USA300 BSI isolates in a murine model of BSI. The sarZ mutations derepressed the expression and production of the surface protein ClfB, which was critical for the pathogenesis of USA300 BSI isolates. Altogether, these findings highlight ongoing evolution of a major MRSA lineage and suggest USA300 strains can optimize their fitness through altered regulation of virulence.

Original languageEnglish
Pages (from-to)228-242.e8
JournalCell Host and Microbe
Volume31
Issue number2
DOIs
StatePublished - 8 Feb 2023

Keywords

  • GWAS
  • MRSA
  • SarZ
  • USA300
  • bloodstream infections
  • gene regulation
  • pathogenesis
  • virulence

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