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Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation

Author

Listed:
  • Kira L. Tomlinson

    (Columbia University)

  • Tania Wong Fok Lung

    (Columbia University)

  • Felix Dach

    (Columbia University
    University Hospital)

  • Medini K. Annavajhala

    (Columbia University)

  • Stanislaw J. Gabryszewski

    (Columbia University)

  • Ryan A. Groves

    (University of Calgary)

  • Marija Drikic

    (University of Calgary)

  • Nancy J. Francoeur

    (Mt. Sinai Icahn School of Medicine)

  • Shwetha H. Sridhar

    (Mt. Sinai Icahn School of Medicine)

  • Melissa L. Smith

    (Mt. Sinai Icahn School of Medicine)

  • Sara Khanal

    (Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine)

  • Clemente J. Britto

    (Section of Pulmonary, Critical Care, and Sleep Medicine, Yale University School of Medicine)

  • Robert Sebra

    (Mt. Sinai Icahn School of Medicine)

  • Ian Lewis

    (University of Calgary)

  • Anne-Catrin Uhlemann

    (Columbia University)

  • Barbara C. Kahl

    (University Hospital)

  • Alice S. Prince

    (Columbia University)

  • Sebastián A. Riquelme

    (Columbia University)

Abstract

Staphylococcus aureus is a prominent human pathogen that readily adapts to host immune defenses. Here, we show that, in contrast to Gram-negative pathogens, S. aureus induces a distinct airway immunometabolic response dominated by the release of the electrophilic metabolite, itaconate. The itaconate synthetic enzyme, IRG1, is activated by host mitochondrial stress, which is induced by staphylococcal glycolysis. Itaconate inhibits S. aureus glycolysis and selects for strains that re-direct carbon flux to fuel extracellular polysaccharide (EPS) synthesis and biofilm formation. Itaconate-adapted strains, as illustrated by S. aureus isolates from chronic airway infection, exhibit decreased glycolytic activity, high EPS production, and proficient biofilm formation even before itaconate stimulation. S. aureus thus adapts to the itaconate-dominated immunometabolic response by producing biofilms, which are associated with chronic infection of the human airway.

Suggested Citation

  • Kira L. Tomlinson & Tania Wong Fok Lung & Felix Dach & Medini K. Annavajhala & Stanislaw J. Gabryszewski & Ryan A. Groves & Marija Drikic & Nancy J. Francoeur & Shwetha H. Sridhar & Melissa L. Smith &, 2021. "Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21718-y
    DOI: 10.1038/s41467-021-21718-y
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    Cited by:

    1. Zachary Roy & Prabakar Arumugam & Blake P. Bertrand & Dhananjay D. Shinde & Vinai C. Thomas & Tammy Kielian, 2024. "Tissue niche influences immune and metabolic profiles to Staphylococcus aureus biofilm infection," Nature Communications, Nature, vol. 15(1), pages 1-20, December.

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