Regulation of the multiple polysaccharides of Bacteroides fragilis

拟杆菌属是人类肠道微生物群中数量上占优势的属之一， 作为互惠共生体，为哺乳动物宿主提供有益的功能。如果脆弱拟杆菌 由于肠屏障的自然破坏而进入否则无菌的腹膜腔， 创伤或手术情况下，它可以成为一个机会致病菌。事实上，B。fragilis是 临床感染中最常见的厌氧菌。B.脆弱拟 已经被证明是有助于这种生物体的能力，既提供共生效益， 哺乳动物宿主在其天然肠道生态位中的免疫缺陷，并且如果其获得进入肠外部位则引起疾病。 长期的目标是了解这种复杂的荚膜多糖是如何在体内合成的。 肠和腹膜腔，以更好地了解它们对共生和毒力的贡献。 目标将解决荚膜多糖合成的多个水平的调节。在 特别是，目标1将分析一组因素抑制能力的机制， 它们各自的多糖生物合成基因座的转录终止。目标2将分析 一组新的转录抑制因子能够干扰 特异性荚膜多糖。目的3将解决一个以前未描述的细胞外的合成 将在表型和转录水平上进行分析。最后，表达 每一种多糖，由DNA倒位引起的启动子方向决定，将从 从相关体内部位分离的细菌。

The Bacteroides are one of the numerically dominant genera of the human intestinal microbiota where they serve as mutualistic symbionts providing beneficial functions to the mammalian host. If Bacteroides fragilis gains access to the otherwise sterile peritoneal cavity due to a breach in the intestinal barrier from natural, traumatic, or surgical circumstances, it can become an opportunistic pathogen. In fact, B. fragilis is one of the most commonly isolated anaerobes from clinical infections. The capsular polysaccharides of B. fragilis have been shown to be instrumental in the ability of this organism to both provide symbiotic benefits to the mammalian host in its natural intestinal niche, and to cause disease if it gains access to extraintestinal sites. The long term objective is to understand how this complex set of capsular polysaccharides is synthesized in both the intestine and peritoneal cavity to better appreciate their contributions to symbiosis and virulence. The aims will address the many levels of regulation of the synthesis of the capsular polysaccharides. In particular, Aim 1 will analyze the mechanisms governing the ability of a set of factors to repress transcriptional termination of their respective polysaccharide biosynthesis loci. Aim 2 will analyze the mechanisms by which a set of novel transcriptional repressors are able to interfere with the expression of specific capsular polysaccharides. Aim 3 will address the synthesis of a previously undescribed extracellular polysaccharide which will be analyzed at the phenotypic and transcriptional levels. Lastly, the expression of each of the polysaccharides, dictated by promoter orientation due to DNA inversions, will be studied from bacteria isolated from relevant in vivo sites.