Analysis of Type VI Secretion in Burkholderia pseudomallei

鼻疽伯克霍尔德杆菌VI型分泌物分析

• 批准号: 8236994
• 负责人: Joseph David Mougous
• 金额: $ 29.78万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-03-01 至 2014-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8236994
• 关键词: Accounting; Acute; Aerosols; Antibiotics; Area; Australia; Bacteria; Biochemical Genetics; Biological Assay; Burkholderia pseudomallei; Categories; Centers for Disease Control and Prevention (U.S.); Centers of Research Excellence; Code; Complement; Complex; Disease; Emerging Communicable Diseases; Foundations; Future; Genome; Genomics; Goals; Gram-Negative Bacteria; Infection; Investigation; Laboratories; Laboratory culture; Lead; Measures; Melioidosis; Methods; Mission; Modeling; Mus; Mutation; Organism; Pathogenesis; Pathway interactions; Phenotype; Play; Post-Translational Regulation; Protein Secretion; Protein translocation; Proteins; Pseudomonas aeruginosa; Recruitment Activity; Regulation; Regulatory Pathway; Reporter; Research; Resistance; Role; Route; Serine; Solid; Southeastern Asia; System; Testing; Therapeutic Intervention; Threonine; Virulence; Virulence Factors; Work; base; biodefense; defined contribution; experience; gene replacement; insight; macrophage; mortality; novel; pathogen; pathogenic bacteria; secretion process; tool

Pathogenic bacteria make extensive use of secreted proteins in order to colonize and persist in their hosts. Recently, a type VI protein secretion system (T6SS) of Burkholderia pseudomallei, the causative agent of melioidosis, was shown to be a major virulence determinant of the organism. The mechanistic basis for the role of T6S in B. pseudomallei whence is not known. Interestingly, the genome of this organism encodes five additional T6SSs that have not been investigated; accounting for greater than 2% of its genomic coding capacity. Given the widespread relevance of this protein translocation system in bacteria-host interactions, it is likely that these additional T6SSs also play critical roles for this organism. Having discovered T6S in the closely related organism Pseudomonas aeruginosa, the project leader of this proposal, Dr. Joseph Mougous, has demonstrated expertise in this field of research. The focus of this proposal is to characterize several aspects of the T6SSs of B. pseudomallei. In Aim 1, the involvement of each system in virulence and host interactions will be measured. Aim 2 will identify regulatory pathways of the systems, and investigate the role of a predicted post-translational control mechanism. In the final aim, novel T6S substrates will be identified by a quantitative mass spectrometric approach. The phenotypic profile of each secretion system, the identification of regulators, and the identities of T6S substrates, will provide a solid foundation for future investigation of T6S in this organism.

致病细菌广泛利用分泌的蛋白质来在宿主体内定殖并持续存在。 最近，类鼻疽伯克霍尔德氏菌 (Burkholderia pseudomallei) 的 VI 型蛋白分泌系统 (T6SS) 被证实是 类鼻疽被证明是该生物体的主要毒力决定因素。其机制基础 T6S 在类鼻疽杆菌中的作用尚不清楚。有趣的是，这种生物体的基因组编码 另外五个尚未调查的 T6SS；占其基因组编码的2%以上 容量。鉴于这种蛋白质易位系统在细菌-宿主相互作用中的广泛相关性，它 这些额外的 T6SS 很可能对该生物体也发挥着关键作用。发现T6S后 密切相关的有机体铜绿假单胞菌，该提案的项目负责人 Joseph Mougous 博士， 已展示了该研究领域的专业知识。该提案的重点是描述几个特征 类鼻疽杆菌的 T6SS 方面。在目标 1 中，每个系统参与毒力和宿主 将测量相互作用。目标 2 将确定系统的监管途径，并调查 预测的翻译后控制机制的作用。最终目标是，新型 T6S 基板将 通过定量质谱方法鉴定。每个分泌系统的表型特征， 监管机构的识别以及T6S底物的身份，将为未来提供坚实的基础 对该生物体中 T6S 的研究。