Regulation of the multiple polysaccharides of Bacteroides fragilis

类杆菌是人类肠道微生物区系中数量占优势的属之一，它们 作为互惠共生体，为哺乳动物宿主提供有益的功能。如果脆弱类杆菌 进入原本无菌的腹膜腔是由于天然的肠道屏障被破坏， 在创伤性或外科手术的情况下，它可以成为一种机会性的病原体。事实上，脆弱假单胞菌是 临床感染中最常见的厌氧菌。脆弱假单胞菌的荚膜多糖 已经被证明在这种有机体的能力中起到了重要作用，既为 哺乳动物在其自然的肠道生态位中寄生，如果它能进入肠外部位就会引起疾病。 长期目标是了解这组复杂的胶囊多糖是如何在 肠道和腹膜腔，以更好地认识到它们对共生和毒力的贡献。 这些目标将涉及对胶囊多糖合成的多个水平的调节。在……里面 特别是，目标1将分析控制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。Aim 2将分析 一组新的转录抑制物能够干扰基因表达的机制 特定的胶囊多糖。目标3将讨论以前未描述的胞外物质的合成 将在表型和转录水平上进行分析的多糖。最后，表达了 每一种多糖，由于DNA倒置而由启动子方向决定，将从 从体内相关部位分离的细菌。

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.