Hayward R D, Koronakis V
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
EMBO J. 1999 Sep 15;18(18):4926-34. doi: 10.1093/emboj/18.18.4926.
Salmonella causes severe gastroenteritis in humans, entering non-phagocytic cells to initiate intracellular replication. Bacterial engulfment occurs by macropinocytosis, which is dependent upon nucleation of host cell actin polymerization and condensation ('bundling') of actin filaments into cables. This is stimulated by contact-induced delivery of an array of bacterial effector proteins, including the four Sips (Salmonella invasion proteins). Here we show in vitro that SipC bundles actin filaments independently of host cell components, a previously unknown pathogen activity. Bundling is directed by the SipC N-terminal domain, while additionally the C-terminal domain nucleates actin polymerization, an activity so far known only in eukaryotic proteins. The ability of SipC to cause actin condensation and cytoskeletal rearrangements was confirmed in vivo by microinjection into cultured cells, although as SipC associates with lipid bilayers it is possible that these activities are normally directed from the host cell membrane. The data suggest a novel mechanism by which a pathogen directly modulates the cytoskeletal architecture of mammalian target cells.
沙门氏菌可导致人类严重肠胃炎，它进入非吞噬细胞以启动细胞内复制。细菌通过巨吞饮作用被吞噬，这依赖于宿主细胞肌动蛋白聚合的成核作用以及肌动蛋白丝凝聚（“成束”）形成束状结构。这一过程由一系列细菌效应蛋白接触诱导传递所刺激，其中包括四种Sip蛋白（沙门氏菌入侵蛋白）。我们在此体外实验中表明，SipC能独立于宿主细胞成分使肌动蛋白丝成束，这是一种此前未知的病原体活性。成束作用由SipC的N端结构域引导，此外，C端结构域能引发肌动蛋白聚合，这种活性迄今为止仅在真核蛋白中发现。通过向培养细胞中显微注射，SipC在体内引发肌动蛋白凝聚和细胞骨架重排的能力得到了证实，不过由于SipC与脂质双层相关联，这些活性有可能通常是从宿主细胞膜引导而来的。这些数据提示了一种病原体直接调节哺乳动物靶细胞细胞骨架结构的新机制。
