PUI RESEARCH-MUW-BRANDON

这个子项目是许多利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 志贺菌是志贺氏菌病（细菌性痢疾的一种形式）的专性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，它们就会复制并招募肌动蛋白丝，以便在这些细胞内定向运动，并随后侵入相邻细胞。 志贺氏菌外膜蛋白，IcsA是志贺氏菌致病所必需的，因为这是唯一的细菌蛋白质所需的招募肌动蛋白丝。 ICSA在所有志贺菌属物种中发现的大的220-β-内酰胺酶毒力质粒上表达。此外，IcsA的独特之处在于它靶向并限制于细菌的旧极。 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运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、靶向芽孢杆菌的旧极、分泌和维持在该极的机制对于解决志贺氏菌的致病性质是重要的。IcsA是一种自动转运的外膜蛋白，靶向志贺氏菌的旧极;在宿主结肠上皮细胞中，肌动蛋白丝组装用于细胞内游泳和细胞间传播的同一极。 几条证据表明，ICSA在分泌前靶向细胞质膜的内表面，并且ICSA在分泌前必须靶向旧极。我们在筛选中利用这些发现来识别IcsA的假定极性靶点。 我们还开发了一种筛选方法，以确定负责ICSA表达和分泌的因子，并确定志贺菌中ICSA和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.