Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation.
Staphylococcus aureus induces an itaconate-dominated immunometabolic response that drives biofilm formation.
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DOI：
10.1038/s41467-021-21718-y
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发表时间：
2021-03-03
影响因子：
16.6
通讯作者：
Riquelme SA
中科院分区：
文献类型：
--
作者：
Tomlinson KL;Lung TWF;Dach F;Annavajhala MK;Gabryszewski SJ;Groves RA;Drikic M;Francoeur NJ;Sridhar SH;Smith ML;Khanal S;Britto CJ;Sebra R;Lewis I;Uhlemann AC;Kahl BC;Prince AS;Riquelme SA
金黄色葡萄球菌（Staphylococcus aureus）是一种很容易适应宿主免疫防御的重要人类病原体。在这里，我们表明，与革兰氏阴性病原体相比，S。金黄色葡萄球菌诱导由亲电代谢物衣康酸盐释放主导的独特气道免疫代谢反应。衣康酸合成酶IRG1被宿主线粒体应激激活，这是由葡萄球菌糖酵解诱导的。衣康酸抑制S.金黄色葡萄球菌糖酵解，并选择重新引导碳通量以促进胞外多糖（EPS）合成和生物膜形成的菌株。衣康酸适应菌株，如S.金黄色葡萄球菌从慢性气道感染分离，表现出降低的糖酵解活性，高EPS生产，和熟练的生物膜形成，甚至在衣康酸刺激。S.因此，金黄色葡萄球菌通过产生与人气道慢性感染相关的生物膜来适应衣康酸盐主导的免疫代谢应答。作者表明，病原体金黄色葡萄球菌诱导了一种独特的气道免疫代谢反应，主要是衣康酸盐的释放。这种代谢产物反过来又增强了S.金黄色葡萄球菌，这可能会促进慢性感染。
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. The authors show that the pathogen Staphylococcus aureus induces a distinct airway immunometabolic response, dominated by release of itaconate. This metabolite, in turn, potentiates extracellular polysaccharide synthesis and biofilm formation in S. aureus, which may facilitate chronic infection.
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