Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation
説明
<jats:title>Abstract</jats:title><jats:p><jats:italic>Staphylococcus aureus</jats:italic> is a prominent human pathogen that readily adapts to host immune defenses. Here, we show that, in contrast to Gram-negative pathogens, <jats:italic>S. aureus</jats:italic> 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 <jats:italic>S. aureus</jats:italic> 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 <jats:italic>S. aureus</jats:italic> isolates from chronic airway infection, exhibit decreased glycolytic activity, high EPS production, and proficient biofilm formation even before itaconate stimulation. <jats:italic>S. aureus</jats:italic> thus adapts to the itaconate-dominated immunometabolic response by producing biofilms, which are associated with chronic infection of the human airway.</jats:p>
収録刊行物
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- Nature Communications
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Nature Communications 12 (1), 2021-03-03
Springer Science and Business Media LLC
