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铜绿假单胞菌避免免疫清除机制
作者:小柯机器人 发布时间:2020/5/20 20:28:04

美国哥伦比亚大学Alice Prince研究组取得最新进展。他们发现铜绿假单胞菌可利用宿主来源的衣康酸酯来重定向其代谢,以促进生物膜形成。这一研究成果发表在2020518日的《细胞-代谢》杂志上。

他们表明铜绿假单胞菌可以利用宿主的免疫反应来维持感染。值得注意的是,与其他机会细菌不同,他们发现铜绿假单胞菌会响应衣康酸酯(一种在感染的肺中宿主大量产生的免疫代谢物)而改变其代谢和免疫刺激特性。

衣康酸酯诱导细菌膜应力,导致脂多糖(LPS)的下调和细胞外多糖(EPS)的上调。这些适应衣康酸的铜绿假单胞菌会积累lptD突变,这有利于衣康酸同化和生物膜的形成。反过来,EPS诱导气管和全身髓样细胞产生衣康酸,从而使宿主对一种允许的慢性感染的免疫反应发生扭曲。因此,在设计疗法时需要考虑铜绿假单胞菌的代谢多功能性。

据悉,铜绿假单胞菌是特别致病的,通常与顽固性肺炎和高死亡率有关。铜绿假单胞菌如何避免免疫清除并在发炎的人类气道中持续存在,对此知之甚少。

附:英文原文

Title: Pseudomonas aeruginosa Utilizes Host-Derived Itaconate to Redirect Its Metabolism to Promote Biofilm Formation

Author: Sebastián A. Riquelme, Kalle Liimatta, Tania Wong Fok Lung, Blanche Fields, Danielle Ahn, David Chen, Carmen Lozano, Yolanda Sáenz, Anne-Catrin Uhlemann, Barbara C. Kahl, Clemente J. Britto, Emily DiMango, Alice Prince

Issue&Volume: 2020-05-18

Abstract: The bacterium Pseudomonas aeruginosa is especially pathogenic, often being associated with intractable pneumonia and highmortality. How P. aeruginosa avoids immune clearance and persists in the inflamed human airway remains poorlyunderstood. In this study, we show that P. aeruginosa can exploit the host immune response to maintain infection. Notably, unlike otheropportunistic bacteria, we found that P. aeruginosa alters its metabolic and immunostimulatory properties in response to itaconate, anabundant host-derived immunometabolite in the infected lung. Itaconate induces bacterialmembrane stress, resulting in downregulation of lipopolysaccharides (LPS) and upregulationof 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, themetabolic versatility of P. aeruginosa needs to be taken into account when designing therapies.

DOI: 10.1016/j.cmet.2020.04.017

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(20)30199-6

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx