Epithelial Responses to Enteric Organisms

描述(申请人提供)：细菌能够建立一种 与真核宿主的广泛互动关系可能是 共生、共生或寄生。在人类中，这种寄生关系 导致显性和隐性疾病。原核生物- 真核生物的相互作用特别多样，临床上相关的是 哺乳动物的肠道，在那里有一个极其复杂的细菌生态系统 与巨大的上皮表面相连。很明显， 寄主和微生物都会影响对方的生理功能 总体上，尽管不是绝对的，但互惠共存。临床 当这样做时，可能会出现特发性炎症性肠病等症状 相互容忍的态度瓦解了。此外，一些细菌已经进化出 直接或间接引起宿主反应的生活方式 组织损伤，因此这些微生物通常被认为是病原体。一个 经典的例子是常见的革兰氏阴性肠道病原体沙门氏菌。这些 生物体是各种临床症状的病因，包括 炎症性腹泻、系统性伤寒、反应性(非传染性) 关节炎和其他以前未被认识到的潜在医学上的重要问题 表现形式。最近的技术发展使大规模、 基因表达的平行分析，或“表达图谱”。这些 方法允许对给定的引起的调节程序进行全基因组分析 刺激物。在这项建议中，我们将采用 细菌感染/移居。在我们建议的大部分研究中，我们 将利用鼠伤寒沙门氏菌，我们已经确定了一种 影响毒力的一系列遗传和环境变量。我们 将分析其他沙门氏菌菌株，包括致病性和非致病性， 总的目标是定义细菌的宿主“表达谱” 对研究寄主相互作用有很大帮助的致病机制 与其他病原体的关系。更重要的是，这些数据将在 在潜在相关的人类疾病中识别这些特征 被已知和未知的生物感染。

DESCRIPTION (provided by applicant): Bacteria are capable of establishing a wide variety of interactive relationships with eukaryotic hosts that may be symbiotic, commensal or parasitic. In humans, such parasitic relationships result in both overt and covert disease. One site where prokaryotic- eukaryotic interactions are particularly diverse and clinically relevant is in the mammalian intestinal tract, where a vastly complex ecosystem of bacteria interfaces with an immense epithelial surface. It has become apparent that both host and microbe influence each other's physiological function to arrange a generally, though not absolutely, mutually beneficial coexistence. Clinical syndromes such as idiopathic inflammatory bowel disease may result when this mutual tolerance breaks down. Furthermore, some bacteria have evolved lifestyles that directly or indirectly elicit host responses characteristic of tissue injury, thus these organisms are generally considered pathogens. A classic example is the common Gram negative enteropathogen Salmonella. These organisms are causal of a variety of clinical syndromes, including inflammatory diarrhea, systemic typhoid fever, reactive (non-infectious) arthritis and potentially, other previously unrecognized, medically important manifestations. Recent technical developments have permitted large-scale, parallel analysis of gene expression, or "expression profiling". These methods allow genome-wide analysis of regulatory programs elicited by given stimuli. In this proposal we will employ the approach of infection/colonization with bacteria. For most of our proposed studies, we will utilize Salmonella typhimurium, for which we have characterized a spectrum of genetic and environmental variables that affect virulence. We will analyze other strains of Salmonella, both pathogenic and non-pathogenic, with the overall goal of defining a host "expression profile" of bacterial pathogenesis that will be of great utility in the study of host interactions with other pathogens. More significantly, these data will be invaluable in the recognition of these signatures in human diseases potentially associated with infection by known and unknown organisms.