The bacterium Pseudomonas aeruginosa is especially pathogenic, often being associated with intractable pneumonia and high mortality. How P. aeruginosa avoids immune clearance and persists in the inflamed human airway remains poorly understood. In this study, we show that P. aeruginosa can exploit the host immune response to maintain infection. Notably, unlike other opportunistic bacteria, we found that P. aeruginosa alters its metabolic and immunostimulatory properties in response to itaconate, an abundant host-derived immunometabolite in the infected lung. Itaconate induces bacterial membrane stress, resulting in downregulation of lipopolysaccharides (LPS) and upregulation of extracellular polysaccharides (EPS). These itaconate-adapted P. aeruginosa accumulate lptD mutations, which favor itaconate assimilation and biofilm formation. EPS, in turn, induces itaconate production by myeloid cells, both in the airway and systemically, skewing the host immune response to one permissive of chronic infection. Thus, the metabolic versatility of P. aeruginosa needs to be taken into account when designing therapies.

细菌绿脓杆菌特别致病的，经常被顽固性肺炎和高死亡率。铜绿假单胞菌如何避免免疫清除并在发炎的人类呼吸道中持续存在仍然知之甚少。在这项研究中，我们表明铜绿假单胞菌可以利用宿主免疫反应来维持感染。值得注意的是，与其他机会性细菌不同，我们发现铜绿假单胞菌衣康酸盐是受感染肺中丰富的宿主衍生免疫代谢物，从而改变其代谢和免疫刺激特性。衣康酸诱导细菌膜应激，导致脂多糖 (LPS) 下调和胞外多糖 (EPS) 上调。这些适应衣康酸的铜绿假单胞菌积累了lptD突变，这有利于衣康酸同化和生物膜形成。反过来，EPS 在气道和全身诱导骨髓细胞产生衣康酸，从而使宿主免疫反应偏向于慢性感染。因此，在设计治疗方法时需要考虑铜绿假单胞菌的代谢多样性。