Lon-Mediated Regulation of Type III Protein Secretion in Pseudomonas Syringae

丁香假单胞菌是一种植物病原菌，其致病性和寄主范围与III型蛋白分泌系统(TTSS)的活动有关，TTSS本质上是将细菌蛋白注入宿主细胞。这些注入的蛋白质改变宿主细胞，以帮助细菌在敏感植物中的生长，但在抗病植物中，这些蛋白质作为启动与抗病相关的细胞防御机制的信号。在与宿主细胞相互作用的过程中，TTSS的组装被诱导，并由复杂的遗传调控系统协调。控制TTSS组装的正负作用调节因子已经被确定。本项目将阐明这些调节因子如何转导在与宿主相互作用过程中产生的信号，以调节和协调TTS的组装。这项研究将确定特定调节蛋白酶的活性在疾病过程中是如何控制的，确定另一种调节蛋白HrpV在协调TTS组装中的作用，研究控制蛋白质何时从细菌中释放的可能的门控机制，并阐明关键转录因子的活性是如何调节的。这些实验将为控制植物细菌性疾病和抗病的分子机制提供新的见解，但由于哺乳动物的几种细菌病原体使用非常相似的机制，这项研究可能会应用于哺乳动物宿主的细菌性疾病的管理。

The pathogenicity and host range of Pseudomonas syringae, a plant pathogenic bacterium, has been linked to the activities of a type III protein secretion system (TTSS) that essentially injects bacterial proteins into cells of its host. These injected proteins alter the host cells to assist the growth of the bacterium in susceptible plants, but in resistant plants these proteins serve as a signal to initiate cellular defense mechanisms associated with disease resistance. The assembly of the TTSS in P. syringae is induced during the interaction with host cells and is coordinated by a complex genetic regulatory system. Positive- and negative-acting regulatory factors that control assembly of the TTSS have been identified. This project will elucidate how these regulatory factors transduce signals produced during the interaction with the host to regulate and coordinate assembly of the TTSS. This research will determine how the activity of a specific regulatory protease is controlled during the disease process, define the role of another regulatory protein, HrpV, in coordinating the assembly of the TTSS, examine a possible gating mechanism controlling when proteins are released from the bacteria, and elucidate how the activities of key transcriptional factors are modulated. The proposed experiments will provide new insight into molecular mechanisms for controlling bacterial disease and disease resistance in plants, but since several bacterial pathogens of mammals use a very similar mechanism, this research may have application to managing bacterial diseases of mammalian hosts.