Swistak Léa, Albert Marvin, Valenzuela Camila, Gokerkucuk Elif Begum, Bontems François, Tachon Stéphane, Egger Keith T, Gazi Anastasia D, Sartori-Rupp Anna, Lesser Cammie F, Paul-Gilloteaux Perrine, Tinevez Jean-Yves, Vos Matthijn, Enninga Jost
Institut Pasteur, Université Paris Cité, CNRS UMR3691, Dynamics of Host-Pathogen Interactions Unit, Paris, France.
Institut Pasteur, Université Paris Cité, Image Analysis Hub, Paris, France.
PLoS Biol. 2025 May 1;23(5):e3003135. doi: 10.1371/journal.pbio.3003135. eCollection 2025 May.
Endomembrane breaching is a crucial strategy employed by intracellular pathogens enclosed within vacuoles to access the nutrient-rich cytosol for intracellular replication. While bacteria use various mechanisms to compromise host membranes, the specific processes and factors involved are often unknown. Shigella flexneri, a major human pathogen, accesses the cytosol relying on the Type Three Secretion System (T3SS) and secreted effectors. Using in-cell correlative light and electron microscopy, we tracked the sequential steps of Shigella host cell entry. Moreover, we captured the T3SS, which projects a needle from the bacterial surface, in the process of puncturing holes in the vacuolar membrane. This initial puncture ensures disruption of the vacuole. Together this introduces the concept of mechanoporation via a bacterial secretion system as a crucial process for bacterial pathogen-induced membrane damage.
内膜突破是被包裹在液泡中的细胞内病原体采用的一种关键策略，目的是进入富含营养的胞质溶胶进行细胞内复制。虽然细菌利用各种机制破坏宿主膜，但其中涉及的具体过程和因素往往尚不明确。福氏志贺菌是一种主要的人类病原体，它依靠三型分泌系统（T3SS）和分泌的效应蛋白进入胞质溶胶。我们利用细胞内相关光电子显微镜追踪了福氏志贺菌进入宿主细胞的连续步骤。此外，我们捕捉到了从细菌表面伸出针状结构的三型分泌系统在液泡膜上打孔的过程。这一初始穿刺确保了液泡的破坏。这些共同引入了通过细菌分泌系统进行机械穿孔的概念，这是细菌病原体诱导膜损伤的一个关键过程。
