Oleate Hydratase (OhyA) Is a Virulence Determinant in Staphylococcus aureus

Christopher D. Radka, Justin L. Batte, Matthew W. Frank, Jason W. Rosch, Charles O. Rock

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Staphylococcus aureus is an important pathogen that relies on a variety of mechanisms to evade and counteract the immune system. We show that S. aureus uses oleate hydratase (OhyA) to convert host cis-9 unsaturated fatty acids to their 10-hydroxy derivatives in human serum and at the infection site in a mouse neutropenic thigh model. Wild-type and DohyA strains were equally infective in the neutropenic thigh model, but recovery of the DohyA strain was 2 orders of magnitude lower in the immunocompetent skin infection model. Despite the lower bacterial abundance at the infection site, the levels of interleukin 6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), IL-1b, and tumor necrosis factor alpha (TNF-a) elicited by the DohyA strain were as robust as those of either the wild-type or the complemented strain, indicating that the immune system was more highly activated by the DohyA strain. Thus, OhyA functions to promote S. aureus virulence. IMPORTANCE The oleate hydratase protein family was discovered in commensal bacteria that utilize host unsaturated fatty acids as the substrates to produce a spectrum of hydroxylated products. These hydroxy fatty acids are thought to act as signaling molecules that suppress the inflammatory response to create a more tolerant environment for the microbiome. S. aureus is a significant human pathogen, and defining the mechanisms used to evade the immune response is critical to understanding pathogenesis. S. aureus expresses an OhyA that produces at least three 10-hydroxy fatty acids from host unsaturated fatty acids at the infection site, and an S. aureus strain lacking the ohyA gene has compromised virulence in an immunocompetent infection model. These data suggest that OhyA plays a role in immune modulation in S. aureus pathogenesis similar to that in commensal bacteria.

Original languageEnglish
Article numbere01546
JournalMicrobiology spectrum
Volume9
Issue number3
DOIs
StatePublished - Dec 2021

Bibliographical note

Publisher Copyright:
Copyright © 2021 Radka et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.

Keywords

  • Hydroxy fatty acids
  • Oleate hydratase
  • Soft tissue infection
  • Staphylococcus aureus
  • Unsaturated fatty acids
  • Virulence
  • Virulence determinants

ASJC Scopus subject areas

  • Physiology
  • Ecology
  • General Immunology and Microbiology
  • Genetics
  • Microbiology (medical)
  • Cell Biology
  • Infectious Diseases

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