A Novel Surface Sensing Pathway in Proteus mirabilis

奇异变形杆菌中的新型表面传感途径

• 批准号: 8597943
• 负责人: Philip N. Rather
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-10-01 至 2016-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8597943
• 关键词: Address; Affect; Agar; Bacteria; Biochemical; Catheterization; Catheters; Cell Differentiation process; Cell division; Cell physiology; Cells; Complex; Elderly; Enterobacteriaceae; Funding; Gene Expression Regulation; Genes; Genetic; Gram-Negative Bacteria; Growth; Hospitalization; Infection; Lead; Membrane; Microbial Biofilms; Mirabilis; Molecular; Nosocomial Infections; Nursing Homes; O Antigens; Pathway interactions; Patients; Population; Process; Proteins; Proteus mirabilis; Regulon; Role; Salmonella typhimurium; Signal Pathway; Signal Transduction; Solid; Spinal cord injury; Surface; Surface Properties; Techniques; Urinary Calculi; Urinary Incontinence; Urinary tract infection; Veterans; Virulence; Work; base; biophysical techniques; follow-up; member; novel; prevent; prostatitis; protein B; protein protein interaction; public health relevance; response; retinal rods; transcriptome sequencing

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.

描述（由申请人提供）： 尿路感染，包括前列腺炎和传染性尿路结石，影响着我们很大一部分退伍军人。这些感染会使人衰弱，一旦发生就极难治疗。革兰氏阴性细菌奇异变形杆菌是尿路感染的主要原因，尤其是在接受广泛导尿的患者中，例如老年疗养院患者和脊髓损伤患者。当在固体表面（例如福利导管或琼脂平板）上生长时，奇异果会经历复杂的形态变化，其中细胞从典型的革兰氏阴性杆状细胞（营养细胞）分化为高度伸长的群集细胞。分化能力对于这种细菌的毒力和形成结晶生物膜的能力很重要。奇异果识别表面并启动群细胞分化的机制在很大程度上尚不清楚。该提案将研究在上一资助期间发现的一种新的信号传导途径，该途径允许奇异果使用 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，从而激活群体细胞分化。此外，Rcs 调节子中编码细胞功能的基因 群体细胞分化直接所需的作用，例如伸长和细胞分裂的抑制，尚不清楚。 为了解决这一差距，RNA-Seq 将用于识别受反应调节器 RcsB 特异性调节的基因。