Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA, USA.
Cell Microbiol. 2013 Nov;15(11):1796-808. doi: 10.1111/cmi.12179. Epub 2013 Sep 3.
Enteropathogenic and enterohaemorrhagic Escherichia coli use a novel infection strategy to colonize the gut epithelium, involving translocation of their own receptor, Tir, via a type III secretion system and subsequent formation of attaching and effecting (A/E) lesions. Following integration into the host cell plasma membrane of cultured cells, and clustering by the outer membrane adhesin intimin, Tir triggers multiple actin polymerization pathways involving host and bacterial adaptor proteins that converge on the host Arp2/3 actin nucleator. Although initially thought to be involved in A/E lesion formation, recent data have shown that the known Tir-induced actin polymerization pathways are dispensable for this activity, but can play other major roles in colonization efficiency, in vivo fitness and systemic disease. In this review we summarize the roadmap leading from the discovery of Tir, through the different actin polymerization pathways it triggers, to our current understanding of their physiological functions.
肠致病性和肠出血性大肠杆菌使用一种新颖的感染策略来定殖肠道上皮细胞,涉及通过 III 型分泌系统易位其自身的受体 Tir,随后形成附着和效应(A/E)病变。在培养细胞的宿主细胞质膜中整合,并通过外膜黏附素 intimin 聚类后,Tir 触发涉及宿主和细菌衔接蛋白的多种肌动蛋白聚合途径,这些途径汇聚到宿主 Arp2/3 肌动蛋白成核因子上。尽管最初认为 Tir 诱导的肌动蛋白聚合途径参与 A/E 病变的形成,但最近的数据表明,已知的 Tir 诱导的肌动蛋白聚合途径对于这种活性是可有可无的,但可以在定植效率、体内适应性和全身性疾病中发挥其他主要作用。在这篇综述中,我们总结了从 Tir 的发现,到它引发的不同肌动蛋白聚合途径,再到我们目前对其生理功能的理解的路线图。