PUI RESEARCH-MUW-BRANDON

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 志贺氏菌属是志贺氏菌病(细菌性痢疾的一种形式)的专有细胞内病原体和病原体，估计每年造成110万人死亡。志贺氏菌的发病机制涉及结肠上皮细胞的侵袭。一旦细菌进入细胞，它们就会复制和招募肌动蛋白细丝，以便在这些细胞内定向移动，并随后入侵邻近的细胞。志贺氏菌外膜蛋白ICSA是志贺氏菌致病所必需的，因为它是肌动蛋白细丝募集所需的唯一细菌蛋白。ICSA在一个大的220kb的毒力质粒上表达，在所有种类的志贺氏菌中都存在。此外，ICSA的独特之处在于它的靶点和限制在细菌的老极点。初步研究表明，ICSA的不对称分布与志贺氏菌在结肠上皮细胞内的定向移动及其向未感染细胞的有效传播直接相关。因此，了解ICSA表达、针对旧杆状杆菌、在杆状杆菌分泌和维持的机制，对于解决志贺氏菌的致病性质是重要的。ICSA是一种自动运输的外膜蛋白，定位于志贺氏菌的旧极；在宿主结肠上皮细胞中，肌动蛋白细丝在同一极组装，用于细胞内游泳和细胞间扩散。有几条证据表明，ICSA在分泌之前定位于细胞质膜的内面，而且ICSA在分泌之前必须定位于旧极。我们利用这些发现在筛查中确定了ICSA的一个假定的极地目标。我们还开发了一种筛查，以确定导致ICSA表达和分泌的因素，并确定ICSA和志贺氏菌中其他毒力蛋白的全球调节因子。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Shigella spp. are obligate intracellular pathogens and causative agents of shigellosis (a form of bacillary dysentery) that causes an estimated 1.1 million deaths per annum. The pathogenesis of Shigella involves the invasion of colonic epithelial cells. Once the bacteria have entered a cell they replicate and recruit actin filaments for directional movement within these cells and for subsequent invasion of adjacent cells. The Shigella outer membrane protein, IcsA is essential to Shigella pathogenesis in that this is the sole bacterial protein required for the recruitment of actin filaments. IcsA is expressed on a large 220-kilobase virulence plasmid found in all species of Shigella. Furthermore, IcsA is unique in that it is targeted and restricted to the old pole of the bacterium. Preliminary studies indicate that the asymmetrical distribution of IcsA is directly correlated with directional movement of Shigella within colonic epithelial cells and its efficient dissemination to uninfected cells. Therefore an understanding of the mechanisms by which IcsA is expressed, targeted to the old pole of the bacillus, secreted and maintained at the pole is important in addressing the pathogenic nature of Shigella. IcsA, an autotransported outer membrane protein is targeted to the old pole of the Shigella; the same pole where actin filaments are assembled for intracellular swimming and intercellular dissemination in host colonic epithelial cells. Several lines of evidence suggests that IcsA is targeted to the inner face of the cytoplasmic membrane before secretion and that IcsA must be targeted to the old pole before it is secreted. We have exploited these findings in a screen to identify a putative polar target for IcsA. We have also developed a screen to identify factors that are responsible for the expression and secretion of IcsA and to identify global regulators of IcsA and other virulence proteins in Shigella.