A Novel Surface Sensing Pathway in Proteus mirabilis

描述(由申请人提供)： 尿路感染，包括前列腺炎和感染性尿结石，影响着我们退伍军人人口的很大比例。这些感染使人虚弱，一旦确诊，可能极难治疗。革兰氏阴性杆菌奇异变形杆菌是尿路感染的主要原因，特别是在接受广泛导尿的患者中，如老年疗养院患者和脊髓损伤患者。当生长在固体表面，如Foley导管或琼脂平板时，奇异P.mirabilis经历了复杂的形态变化，细胞从典型的革兰氏阴性杆状细胞(营养细胞)分化为高度伸长的沼泽细胞。分化的能力对于这种细菌的毒力和形成结晶生物膜的能力是重要的。奇异P.mirabilis识别表面并启动群集细胞分化的机制在很大程度上是未知的。这项提议将研究一种新的信号通路，该通路在之前的资金支持期间被发现，该通路允许奇异革兰氏菌使用O-抗原感知表面，通过RCSF、UmoD/B蛋白和RCS磷酸继电器启动信号转导级联，激活沼泽细胞分化。此外，RCS调节子中编码细胞功能的基因 游动细胞的直接分化所需的伸长和抑制细胞分裂等都是未知的。为了解决这一差距，RNA-Seq将被用于识别由反应调节因子RCSB具体调控的基因。

DESCRIPTION (provided by applicant): Urinary tract infections, including prostatitis and infectious urinary stones, affect a large percentage of our veteran population. These infections are debilitating and once established can be extremely difficult to treat. The Gram-negative bacterium Proteus mirabilis is a leading cause of urinary tract infections, especially in patients undergoing extensive catheterization, such as elderly nursing home patients and those with spinal cord injuries. When grown on solid surfaces, such as Foley catheters or agar plates, P. mirabilis undergoes a complex morphological change, where cells differentiate from the typical gram- negative rod (vegetative cells) into highly elongated swarmer cells. The ability to differentiate is important for the virulence of this bacterium and for the ability to form crystalline biofilms. The mechanisms by which P. mirabilis recognizes surfaces and initiates swarmer cell differentiation are largely unknown. This proposal will investigate a novel signaling pathway identified in the previous funding period that allows P. mirabilis to sense surfaces using O-antigen to initiate a signal transduction cascade via RcsF, the UmoD/B proteins and the Rcs phosphorelay to activate swarmer cell differentiation. In addition, genes in the Rcs regulon that encode cellular functions directly required for swarmer cell differentiation, such as elongation and the inhibition of cell division are unknown. To address this gap, RNA-Seq will be used to identify genes that are specifically regulated by the response regulator RcsB.