Miao E A, Miller S I
Department of Microbiology, University of Washington, HSB K-140, Box 357710, Seattle, WA 98195, USA.
Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7539-44. doi: 10.1073/pnas.97.13.7539.
Type III secretion systems (TTSS) are important virulence factors that Gram-negative bacteria use to translocate proteins into the cytoplasm of eukaryotic host cells. Salmonellae encode two virulence-associated TTSS. The Salmonella pathogenicity island 1 (SPI1)-encoded TTSS is active on contact with host cells, whereas the Salmonella pathogenicity island 2 (SPI2)-encoded TTSS is expressed after phagocytosis of bacteria by host cells. Previously, no consensus signal sequence for translocation has been identified among TTSS effector proteins. In this work, seven proteins, termed Salmonella-translocated effectors (STE), are described that contain conserved amino acid sequences that direct translocation by TTSS in Salmonella typhimurium. STE that are coordinately regulated with SPI2 gene expression contain translocation signals that are recognized by the SPI2 but not by the SPI1 TTSS. STE that are constitutively expressed contain signals that direct translocation through both SPI1 and SPI2 TTSS. Of the seven STE examined, SspH1 and SspH2 have been previously shown to be translocated and involved in virulence; SlrP and SifA were identified as virulence factors, but were not previously known to be associated with TTSS; and SseI, SseJ, and SifB were previously unidentified. Three STE genes (sspH1, sspH2, and sseI) are located within temperate bacteriophages, suggesting a common mechanism for the dissemination of more recently evolved STE.
III型分泌系统(TTSS)是革兰氏阴性菌用于将蛋白质转运到真核宿主细胞胞质中的重要毒力因子。沙门氏菌编码两种与毒力相关的TTSS。沙门氏菌致病岛1(SPI1)编码的TTSS在与宿主细胞接触时激活,而沙门氏菌致病岛2(SPI2)编码的TTSS在宿主细胞吞噬细菌后表达。此前,在TTSS效应蛋白中尚未鉴定出用于转运的共有信号序列。在这项研究中,描述了七种被称为沙门氏菌转运效应蛋白(STE)的蛋白质,它们含有保守氨基酸序列,可指导鼠伤寒沙门氏菌中的TTSS进行转运。与SPI2基因表达协同调控的STE含有可被SPI2识别但不能被SPI1 TTSS识别的转运信号。组成型表达的STE含有可指导通过SPI1和SPI2 TTSS进行转运的信号。在所检测的七种STE中,SspH1和SspH2先前已被证明可被转运并参与毒力;SlrP和SifA被鉴定为毒力因子,但此前未知与TTSS相关;而SseI、SseJ和SifB此前未被鉴定。三个STE基因(sspH1、sspH2和sseI)位于温和噬菌体中,这表明了一种传播最近进化的STE的共同机制。