Simon Fraser University, Burnaby, BC, Canada.
BMC Microbiol. 2012 Mar 16;12:36. doi: 10.1186/1471-2180-12-36.
The spectrin cytoskeleton is emerging as an important host cell target of enteric bacterial pathogens. Recent studies have identified a crucial role for spectrin and its associated proteins during key pathogenic processes of Listeria monocytogenes and Salmonella Typhimurium infections. Here we investigate the involvement of spectrin cytoskeletal components during the pathogenesis of the invasive pathogen Shigella flexneri.
Immunofluorescent microscopy reveals that protein 4.1 (p4.1), but not adducin or spectrin, is robustly recruited to sites of S. flexneri membrane ruffling during epithelial cell invasion. Through siRNA-mediated knockdowns, we identify an important role for spectrin and the associated proteins adducin and p4.1 during S. flexneri invasion. Following internalization, all three proteins are recruited to the internalized bacteria, however upon generation of actin-rich comet tails, we observed spectrin recruitment to those structures in the absence of adducin or p4.1.
These findings highlight the importance of the spectrin cytoskeletal network during S. flexneri pathogenesis and further demonstrate that pathogenic events that were once thought to exclusively recruit the actin cytoskeletal system require additional cytoskeletal networks.
血影蛋白细胞骨架正在成为肠道细菌病原体的重要宿主细胞靶标。最近的研究已经确定了血影蛋白及其相关蛋白在李斯特菌和沙门氏菌感染的关键致病过程中的关键作用。在这里,我们研究了血影蛋白细胞骨架成分在侵袭性病原体福氏志贺菌发病机制中的参与情况。
免疫荧光显微镜显示,在福氏志贺菌侵袭上皮细胞过程中,蛋白 4.1(p4.1)而不是内收蛋白或血影蛋白强烈募集到膜皱襞部位。通过 siRNA 介导的敲低,我们确定了血影蛋白以及相关蛋白内收蛋白和 p4.1 在福氏志贺菌侵袭中的重要作用。内化后,这三种蛋白都被招募到内化的细菌中,然而,在形成富含肌动蛋白的彗星尾巴时,我们观察到在没有内收蛋白或 p4.1 的情况下,血影蛋白被招募到这些结构中。
这些发现强调了血影蛋白细胞骨架网络在福氏志贺菌发病机制中的重要性,并进一步表明,曾经被认为仅募集肌动蛋白细胞骨架系统的致病事件需要其他细胞骨架网络。