Mechanisms of Yersinia Pathogenesis
Mechanisms of Yersinia Pathogenesis
批准号:
7645351
负责人:
Ruslan Medzhitov
金额:
$26.32万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
已结题
起止时间:
2008-03-01 至 2009-02-28
关键词:
AccountingAddressAmino AcidsAntigen PresentationAntigensApoptoticCell DeathCellsDendritic CellsDependenceDoctor of PhilosophyEngineeringEquilibriumFundingHost resistanceImmuneImmune responseImmunityIndividualInfectionInfectious AgentLiteratureMapsMethodsMitogen-Activated Protein KinasesModelingMolecularMonitorMusNF-kappa BOrganismPasteurella pseudotuberculosisPathogenesisPathologyPathway interactionsPlasmidsPlayPositioning AttributePredispositionProcessProteinsPurposeRoleSerotypingSystemT-LymphocyteTestingTransgenic MiceTransgenic OrganismsViralVirulenceVirulence FactorsVirulentYersiniaYersinia enterocoliticaYersinia pestiscell typecytotoxiccytotoxicityin vivoinsightkillingsloss of function mutationmacrophagemutantnovelpathogenreconstitutionresearch studyresponse
中文摘要
合并项目8:耶尔森氏菌致病机制--Ruslan Medzhitov博士。
被病原体感染后的细胞死亡可能是一种旨在保护宿主的宿主反应
消除细菌或病毒复制的利基,或者这可能是一个由致病毒力诱导的过程
促进病原体传播或消除宿主免疫细胞的因素。在任何一种中
在这种情况下,一种特定的病原生物体可能对导致细胞死亡的程度有一个‘设定点
来自与特定主持人的互动。如何实现这一平衡或设定点是一个尚未解决的问题
使用已建立的功能丧失突变和细菌筛选的方法来解决
毒力因素。了解这一平衡对于治疗由以下原因引起的病理很重要
由于宿主免疫反应的失调而引起的感染源或病理学。世界上的文学
耶尔森氏菌属(Yersinia Field)表明,鼠疫耶尔森氏菌(Yersinia)、鼠疫耶尔森氏菌(Yersinia)和鼠疫耶尔森氏菌(Yersinia)是三个关系密切的致病菌种。
假结核和小肠结肠炎耶尔森氏菌具有不同程度的细胞毒性和病理学,具体取决于
不同血清型的小肠结肠炎耶尔森菌的种类、细胞毒性和病理学甚至不同。
我们最初通过比较高毒力野生型小肠结肠炎耶尔森菌的细胞毒性来研究这个问题。
与一株野生型假结核耶尔森菌同源。我们的结果表明,Y.
假性结核病依赖于限制一种特定毒力因子的分泌,而这对
在增强这种有机体的毒力方面起着重要作用。
英文摘要
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.
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