THE STRUCTURAL BASIS FOR HOST-PATHOGEN INTERACTIONS AS DETERMINED USING SAXS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，但不一定是研究者所在的机构。 肺炎链球菌被描述为目前困扰人类的最重要病原体之一，能够引起包括肺炎和脑膜炎在内的几种致命感染，而产气荚膜梭菌是胃肠炎的第三大最常见原因和食源性感染的第二大最常见死亡原因。这两种革兰氏阳性病原体的毒力机制的一个统一特征是它们依赖于细胞外、细胞表面附着的聚糖降解酶（糖苷水解酶）的武库，这些酶破坏宿主组织中的糖。这些酶的一个显著特征是它们的多模块性;它们具有预测专用于催化、碳水化合物结合、蛋白质-蛋白质相互作用和细菌细胞壁附着的模块。它们的大尺寸和模块化程度是非凡的，有些酶含有多达12个不同的模块。为了帮助理解细菌病原体产生的碳水化合物活性酶的作用，本项目将重点研究这些致病细菌分泌的模块化胞外糖苷水解酶的结构和功能。

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. Streptococcus pneumoniae is described as one of the most important pathogens currently plaguing humans, being able to cause several lethal infections including pneumonia and meningitis, while Clostridium perfringens is the third most frequent cause of gastroenteritis and the second most frequent cause of death from foodborne infection. A unifying feature of the virulence mechanisms of these two Gram-positive pathogens is their reliance on an arsenal of extracellular, cell-surface attached glycan degrading enzymes (glycoside hydrolases) that destroy sugars in host tissue. A striking feature of these enzymes is their multi-modularity; they have modules predicted to be dedicated to catalysis, carbohydrate-binding, protein-protein interactions and bacterial cell-wall attachment. Their large size and extent of modularity is extraordinary, with some enzymes containing up to 12 distinct modules. In order to help understand the role of carbohydrate-active enzymes produced by bacterial pathogens, this project will focus on the structure and function of the modular extracellular glycoside hydrolase enzymes secreted by these disease causing bacteria.