Faris Robert, Koch Rebecca, McCaslin Paige, Challagundla Naveen, Steiert Brianna, Andersen Shelby E, Smith Parker, Jabeena C A, Yau Peter, Rudel Thomas, Weber Mary M
Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
Department of Microbiology, Biocenter, University of Wuerzburg, Wuerzburg, Germany Chair of Microbiology, University of Würzburg, Würzburg, Germany.
bioRxiv. 2025 Mar 16:2025.03.16.643443. doi: 10.1101/2025.03.16.643443.
() infections can lead to severe complications due to the pathogen's ability to evade the host immune response, often resulting in asymptomatic infections. The mechanisms underlying this immune subversion remain incompletely understood but likely involve specific bacterial effector proteins. Here, we identify CT181 as a novel effector that directly binds to Mcl-1, a key regulator of neutrophil survival. While a . CT181 mutant exhibited only modest defects in epithelial cell replication and inclusion development, it was essential for . survival in neutrophils, correlating with Mcl-1 stabilization. Using a murine infection model, we demonstrate that CT181 is required for . colonization and cytokine production . Our findings establish CT181 as the first bacterial effector protein known to bind Mcl-1 to enhance neutrophil survival, revealing a critical strategy by which . promotes immune dysregulation, facilitating bacterial persistence while driving . pathogenesis.
（）感染可因病原体逃避宿主免疫反应的能力而导致严重并发症，常导致无症状感染。这种免疫颠覆的潜在机制仍未完全了解，但可能涉及特定的细菌效应蛋白。在这里，我们鉴定出CT181是一种新型效应蛋白，它直接与中性粒细胞存活的关键调节因子Mcl-1结合。虽然CT181突变体在上皮细胞复制和包涵体形成方面仅表现出适度缺陷，但它对在中性粒细胞中存活至关重要，这与Mcl-1的稳定有关。使用小鼠感染模型，我们证明CT181对于定殖和细胞因子产生是必需的。我们的发现确立了CT181作为已知的第一种结合Mcl-1以增强中性粒细胞存活的细菌效应蛋白，揭示了一种关键策略，通过该策略……促进免疫失调，促进细菌持续存在，同时推动……发病机制。
