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

作者：Kira L. Tomlinson, Tania Wong Fok Lung, Felix Dach, Medini K. Annavajhala, Stanislaw J. Gabryszewski, Ryan A. Groves, Marija Drikic, Nancy J. Francoeur, Shwetha Hara Sridhar, Melissa Laird Smith, Sara Khanal, Clemente J. Britto, Robert Sebra, Ian A. Lewis, Anne‐Catrin Uhlemann, Barbara C. Kahl, Alice S. Prince, Sebastián A. Riquelme · 发表于：Nature Communications · 年份：2021 · DOI：10.1038/s41467-021-21718-y · 被引用次数：160 · 研究领域：Antimicrobial Resistance in Staphylococcus、Bacterial biofilms and quorum sensing、Immune Response and Inflammation

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.