Mechanisms of Yersinia Pathogenesis

合并项目8：耶尔森氏菌致病机制- Ruslan Medzhitov博士 病原微生物感染后的细胞死亡可能是宿主保护宿主的反应 并消除细菌或病毒复制的小生境，或者它可以是由致病性毒力诱导的过程 为了促进病原体的传播或消除宿主免疫细胞的目的，可以使用因子。在任一 在这种情况下，一种特定的致病生物体可能对细胞死亡的程度有一个“设定点”， 与特定宿主的互动。如何实现这种平衡或设定点是一个尚未解决的问题。 然而，使用已建立的功能丧失突变和细菌筛选方法， 毒力因子理解这种平衡对于治疗由以下原因引起的病理是重要的： 感染因子或由宿主免疫应答失调诱导的病理。文学 耶尔森氏菌领域表明，三个密切相关的致病性耶尔森氏菌种，Y。pestis，Y. pseudotuberculosis和Y.小肠结肠炎，有不同程度的细胞毒性和病理学取决于 不同血清型的Y.小肠结肠炎菌种。 我们最初通过比较高毒力野生型Y的细胞毒性来研究这个问题。小肠结肠 野生型Y染色体假结核菌株结果表明，Y. 假结核病依赖于限制一种特定毒力因子的分泌，这在结核病的发生中起着重要作用。 在增强这种生物的毒力方面起着重要作用。

MERGE PROJECT 8: Mechanisms of Yersinia Pathogenesis - Ruslan Medzhitov, Ph.D. Cell death following infection by pathogenic organisms can be a host response intended to protect the host and eliminate a niche for bacterial or viral replication, or it can be a process induced by pathogenic virulence factors for the purpose of promoting spread of the pathogen or the elimination of host immune cells. In either case, a particular pathogenic organism presumably has a 'set-point' for the extent of cell death that results from an interaction with a particular host. How this balance or set-point is achieved is a question that has not yet been addressed using established methods of loss-of-function mutations and screens for bacterial virulence factors. Understanding this balance is important for the treatment of pathologies resulting from either infectious agents or pathology induced by disregulation of host immune responses. Literature in the Yersinia field suggests that the three closely related Yersinia pathogenic species, Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica, have different degrees of cytotoxicity and pathology depending on the species, and that cytotoxicity and pathology even differ among serotypes of the Y. enterocolitica species. We initially examined this problem by comparing cytotoxicity of the highly virulent wild-type Y. enterocolitica with a wild-type Y. pseudotuberculosis strain. Our results indicate that the reduced cytotoxicity of Y. pseudotuberculosis depends on limiting the secretion of a particular virulence factor, and that this plays an important role in enhancing the virulence of this organism.