Center for Bacterial Pathogenesis, Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
Research Scholar Initiative, The Graduate School of Arts and Sciences, Harvard University, Cambridge, MA 02138, USA.
Cell Rep. 2020 Nov 24;33(8):108409. doi: 10.1016/j.celrep.2020.108409.
During infection, some bacterial pathogens invade the eukaryotic cytosol and spread between cells of an epithelial monolayer. Intercellular spread occurs when these pathogens push against the plasma membrane, forming protrusions that are engulfed by adjacent cells. Here, we show that IpaC, a Shigella flexneri type 3 secretion system protein, binds the host cell-adhesion protein β-catenin and facilitates efficient protrusion formation. S. flexneri producing a point mutant of IpaC that cannot interact with β-catenin is defective in protrusion formation and spread. Spread is restored by chemical reduction of intercellular tension or genetic depletion of β-catenin, and the magnitude of the protrusion defect correlates with membrane tension, indicating that IpaC reduces membrane tension, which facilitates protrusion formation. IpaC stabilizes adherens junctions and does not alter β-catenin localization at the membrane. Thus, Shigella, like other bacterial pathogens, reduces intercellular tension to efficiently spread between cells.
在感染过程中，一些细菌病原体侵入真核细胞质，并在单层上皮细胞之间传播。当这些病原体推动质膜时，就会发生细胞间传播，形成被邻近细胞吞噬的突起。在这里，我们表明，志贺氏菌 3 型分泌系统蛋白 IpaC 与宿主细胞黏附蛋白 β-连环蛋白结合，并促进有效的突起形成。不能与 β-连环蛋白相互作用的 IpaC 点突变的志贺氏菌在突起形成和传播方面存在缺陷。通过化学还原细胞间张力或基因耗尽 β-连环蛋白可以恢复传播，突起缺陷的程度与膜张力相关，表明 IpaC 降低了膜张力，从而促进了突起的形成。IpaC 稳定黏着连接，并且不改变 β-连环蛋白在膜上的定位。因此，志贺氏菌与其他细菌病原体一样，通过降低细胞间张力来有效地在细胞间传播。
