Robbins J R, Monack D, McCallum S J, Vegas A, Pham E, Goldberg M B, Theriot J A
Department of Biochemistry, Stanford University School of Medicine, 279 West Campus Drive, Stanford, CA 94305-5307, USA.
Mol Microbiol. 2001 Aug;41(4):861-72. doi: 10.1046/j.1365-2958.2001.02552.x.
The generation and maintenance of subcellular organization in bacteria is critical for many cell processes and properties, including growth, structural integrity and, in pathogens, virulence. Here, we investigate the mechanisms by which the virulence protein IcsA (VirG) is distributed on the bacterial surface to promote efficient transmission of the bacterium Shigella flexneri from one host cell to another. The outer membrane protein IcsA recruits host factors that result in actin filament nucleation and, when concentrated at one bacterial pole, promote unidirectional actin-based motility of the pathogen. We show here that the focused polar gradient of IcsA is generated by its delivery exclusively to one pole followed by lateral diffusion through the outer membrane. The resulting gradient can be modified by altering the composition of the outer membrane either genetically or pharmacologically. The gradient can be reshaped further by the action of the protease IcsP (SopA), whose activity we show to be near uniform on the bacterial surface. Further, we report polar delivery of IcsA in Escherichia coli and Yersinia pseudotuberculosis, suggesting that the mechanism for polar delivery of some outer membrane proteins is conserved across species and that the virulence function of IcsA capitalizes on a more global mechanism for subcellular organization.
细菌中亚细胞组织的形成和维持对于许多细胞过程和特性至关重要，包括生长、结构完整性以及在病原体中的毒力。在此，我们研究了毒力蛋白IcsA（VirG）在细菌表面分布的机制，以促进福氏志贺菌从一个宿主细胞高效传播到另一个宿主细胞。外膜蛋白IcsA招募宿主因子，导致肌动蛋白丝成核，并且当集中在一个细菌极时，促进病原体基于肌动蛋白的单向运动。我们在此表明，IcsA的聚焦极性梯度是通过其仅传递到一个极，随后通过外膜进行侧向扩散而产生的。通过遗传或药理学改变外膜成分可以改变由此产生的梯度。蛋白酶IcsP（SopA）的作用可进一步重塑该梯度，我们证明其活性在细菌表面几乎是均匀的。此外，我们报道了IcsA在大肠杆菌和假结核耶尔森菌中的极性传递，这表明某些外膜蛋白的极性传递机制在物种间是保守的，并且IcsA的毒力功能利用了一种更普遍的亚细胞组织机制。
