Evolutionary Conservation of Interacting Effector Complexes in P. Syringae

丁香假单胞菌相互作用效应复合物的进化保守性

• 批准号: 7383148
• 负责人: David A Baltrus
• 金额: $ 4.68万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7383148
• 关键词: Algorithms; Amaze; Animals; Bacteria; Bioinformatics; Biological Assay; Cataloging; Catalogs; Cells; Complement; Complex; Data; Depth; Development; Disease; Disruption; Environment; Evolution; Fabaceae; Family; Genbank; Genetic; Genomics; Goals; Grouping; Human; Infection; Knock-out; Laboratories; Measurable; Measures; Mentors; Methods; Microbe; Molecular; Nature; Oligonucleotides; Outcome; Pathogenesis; Pathway interactions; Phenotype; Phylogeny; Plants; Proteins; Pseudomonas syringae; Public Health; Range; Relative (related person); Research; Salmonella; Sampling; Shapes; Specificity; Structure; Sum; System; Testing; Time; Virulence; Virulence Factors; Yersinia; base; mutant; pathogen; pathogenic bacteria; preference; programs

DESCRIPTION (provided by applicant): Bacteria employ diverse mechanisms to colonize and co-exist with their eukaryotic hosts. The basis of interaction for many symbiotic and pathogenic bacteria is translocation of multiple effectors into the eukaryotic cellular environment via a type three secretion system (TTSS). Conservation of the TTSS between animal and plant associated microbes highlights the importance of this structure for delivery of effectors across kingdoms. However, it is diversification and evolution of suites of effectors within strains that determines the nature and specificity of interactions with a host. Recent efforts have shown that single strains of bacteria can contain up to 30 effectors, and that the composition of these virulence factors can differ dramatically between isolates of the same species. Despite the importance of effectors in establishing successful infection for human pathogens Salmonella and Yersinia as well as the plant pathogen Pseudomonas syringae, the evolutionary forces that shape the composition of suites of effectors within strains are not well understood. Do effectors generally act independently of one another to cause virulence, or is pathogenesis the outcome of complex interactions between groups of effectors within a host? The goal of this proposal is to understand if and how pairs of effectors interact to promote infection in Pseudomonas syringae. Evolutionary analyses will be used to identify effectors that co-associate with one another between different pathovars of P. syringae. Furthermore, conserved and variable portions of the effector repertoire within one pathovar will be identified through extensive sampling of genetically and geographically diverse isolates using oligonucleotide micro-arrays. Correlation in the presence of effectors through evolutionary time within and between pathovars implies that these effectors interact within the host to cause infection. Once potentially interacting pairs of effectors have been identified, strains containing single and double mutants will be created in order to functionally test for effects on virulence during infection of a host. Relevance To Public Health: Development of disease during infection by many bacteria, such as the human pathogens Salmonella and Yersinia, is entirely dependent on a conserved mechanism employing the translocation of effector proteins from bacterium to host. The goals of this research program are to use evolutionary analyses with the plant pathogen Pseudomonas syringae to identify pairs of effectors that potentially interact within the host and to functionally verify these interactions during infection. This research will therefore provide a greater understanding of the evolutionary forces promoting diversity in suites of effectors within and between bacterial species, and thus virulence within both human and plant hosts.

描述（由申请人提供）：细菌采用不同的机制来定殖并与其真核宿主共存。许多共生菌和致病菌相互作用的基础是多种效应子通过第三型分泌系统（TTSS）易位到真核细胞环境中。动物和植物相关微生物之间TTSS的保守性突出了这种结构对于跨界递送效应物的重要性。然而，正是菌株内效应子套件的多样化和进化决定了与宿主相互作用的性质和特异性。最近的研究表明，单一菌株的细菌可以包含多达30个效应因子，并且这些毒力因子的组成在相同物种的分离株之间可以显着不同。尽管效应子在建立成功感染人类病原体沙门氏菌和耶尔森氏菌以及植物病原体假单胞菌中的重要性，但塑造菌株内效应子组合物的进化力量尚未得到很好的理解。效应子通常是相互独立地作用而引起毒力的吗？或者致病机制是宿主内效应子组之间复杂相互作用的结果？这个建议的目的是了解是否以及如何对效应相互作用，以促进感染假单胞菌。进化分析将被用来确定的效应，相互关联的不同pathovars之间的P. pathovars的。此外，保守的和可变的一个致病变种内的效应库的部分将通过广泛的采样的遗传和地理上不同的分离株使用寡核苷酸微阵列进行鉴定。通过进化时间内和之间的pathovars效应的存在下的相关性意味着这些效应在宿主内相互作用，引起感染。一旦鉴定出潜在的相互作用效应物对，将创建含有单突变体和双突变体的菌株，以在功能上测试在宿主感染期间对毒力的影响。与公共卫生的相关性：在许多细菌（例如人类病原体沙门氏菌和耶尔森氏菌）感染期间疾病的发展完全依赖于采用效应蛋白从细菌到宿主的易位的保守机制。这项研究计划的目标是使用植物病原体假单胞菌的进化分析，以确定对效应器，可能在主机内相互作用，并在感染过程中验证这些相互作用的功能。因此，这项研究将提供一个更好的理解进化的力量，促进多样性的影响内和细菌物种之间的套件，从而在人类和植物宿主的毒力。