Analysis of Type VI Secretion in Burkholderia pseudomallei

病原菌广泛利用分泌蛋白来定殖并在其宿主中持续存在。 最近，类鼻疽伯克霍尔德氏菌的VI型蛋白分泌系统（T6 SS），类鼻疽伯克霍尔德氏菌的病原体， 类鼻疽是该生物体的主要毒力决定因素。的机械基础 T6 S在B中的作用。假鼻疽的来源不明。有趣的是，这种生物的基因组编码 另外5个尚未研究的T6 SS;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， 这些额外的T6 SS可能也对这种生物体起着关键作用。发现了T6 S后， 密切相关的微生物铜绿假单胞菌，本提案的项目负责人约瑟夫·穆戈斯博士， 在这一研究领域有着丰富的经验本建议的重点是描述几个 B的T6 SS的方面。假鼻疽在目标1中，每个系统参与毒力和宿主 互动将被衡量。目标2将确定系统的调节途径，并研究 预测的翻译后控制机制的作用。在最终的目标中，将开发新型T6 S底物。 通过定量质谱法鉴定。每个分泌系统的表型特征， 调节子的鉴定和T6 S底物的鉴定将为未来的研究提供坚实的基础。 T6 S在该生物体中的研究。

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.