Analysis of Type VI Secretion in Burkholderia pseudomallei

病原菌广泛利用分泌蛋白在宿主体内定植和生存。 最近，假腮腺伯克霍尔德氏菌的一种VI型蛋白分泌系统(T6SS)被发现。 类鼻疽病被证明是该生物体的一个主要毒力决定因素。其产生的机制基础是 T6S在假鼻疽杆菌中的作用尚不清楚。有趣的是，这种生物的基因组编码 另外5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很可能也对这种有机体起着关键作用。在发现T6S后， 密切相关的生物铜绿假单胞菌，这项提案的项目负责人约瑟夫·莫格斯博士， 已经在这一研究领域展示了专业知识。这项提案的重点是描述几个 假马利氏杆菌T6SSs的研究在目标1中，每个系统参与毒力和寄主 将测量交互作用。目标2将确定系统的调控途径，并调查 预测的翻译后控制机制的作用。在最终目标中，新型T6S基板将被 通过定量质谱学方法进行鉴定。每个分泌系统的表型特征， 调节剂的识别和T6S底物的识别将为未来提供坚实的基础 该菌中T6S的研究。

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.