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

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, Sara Khanal, Clemente J. Britto, Robert Sebra, Ian Lewis, Anne-Catrin Uhlemann, Barbara C. Kahl, Alice S. Prince and Sebastián A. Riquelme ()
Additional contact information
Kira L. Tomlinson: Columbia University
Tania Wong Fok Lung: Columbia University
Felix Dach: Columbia University
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

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-21718-y

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DOI: 10.1038/s41467-021-21718-y

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