Perrett Charlotte A, Jepson Mark A
Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol, UK.
Cell Microbiol. 2009 Mar;11(3):475-87. doi: 10.1111/j.1462-5822.2008.01268.x. Epub 2008 Dec 11.
The Salmonella pathogenicity island 1 (SPI-1) type three secretion system (TTSS) is essential for Salmonella invasion of host cells through its triggering of actin-dependent membrane ruffles. The SPI-1 effectors SipA, SopE, SopE2 and SopB all have actin regulating activities and contribute to invasion. The precise role of actin regulation by SipA in Salmonella invasion remains controversial since divergent data have been presented regarding the relationship between SipA and membrane ruffling. We hypothesized that the contribution of SipA to membrane ruffling and invasion might vary between Salmonella strains. We compared the effects of SipA deletion on Salmonella enterica serovar Typhimurium (S. Typhimurium) strains that possess or lack SopE. Loss of SipA reduced invasion in the early stages of infection by SopE(+) and SopE(-) strains but the number of membrane ruffles elicited was unaffected. Salmonella strains lacking both SipA and SopE induced ruffles with very different morphology from those induced by wild-type strains or ones lacking single effectors, including the presence of highly dynamic finger-like protrusions and numerous filopodia. A similar phenotype was found for sipA(-)sopE(-), sipA(-)sopE2(-) and sipA(-)sopB(-) mutants. Thus, SipA plays a more prominent role in induction of invasion-competent membrane ruffles by Salmonella lacking a full complement of SPI-1 effectors.
沙门氏菌致病岛1（SPI-1）三型分泌系统（TTSS）对于沙门氏菌通过触发肌动蛋白依赖性膜皱褶侵入宿主细胞至关重要。SPI-1效应蛋白SipA、SopE、SopE2和SopB均具有肌动蛋白调节活性并有助于细菌入侵。由于关于SipA与膜皱褶之间关系的数据存在分歧，SipA在肌动蛋白调节对沙门氏菌入侵中的精确作用仍存在争议。我们推测SipA对膜皱褶和入侵的贡献可能因沙门氏菌菌株而异。我们比较了缺失SipA对具有或缺乏SopE的肠炎沙门氏菌鼠伤寒血清型（鼠伤寒沙门氏菌）菌株的影响。SipA缺失降低了SopE（+）和SopE（-）菌株在感染早期的入侵能力，但引发的膜皱褶数量未受影响。同时缺失SipA和SopE的沙门氏菌菌株诱导产生的皱褶形态与野生型菌株或缺失单个效应蛋白的菌株诱导产生的皱褶形态非常不同，包括出现高度动态的指状突起和大量丝状伪足。在sipA（-）sopE（-）、sipA（-）sopE2（-）和sipA（-）sopB（-）突变体中也发现了类似的表型。因此，在缺乏完整SPI-1效应蛋白的沙门氏菌诱导具有入侵能力的膜皱褶过程中，SipA发挥了更突出的作用。
