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: 8963453
• 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/8963453
• 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; Health; 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; 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，包括前列腺炎和感染性尿路结石，影响了我们的退伍军人人口的很大比例。这些感染会使人虚弱，一旦建立起来就很难治疗。革兰氏阴性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。当在固体表面（如Foley导管或琼脂板）上生长时，奇异变形杆菌经历复杂的形态变化，其中细胞从典型的革兰氏阴性杆菌（营养细胞）分化成高度伸长的群集细胞。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。奇异变形杆菌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。该提案将研究在前一个资助期中确定的一种新的信号传导途径，该途径允许奇异变形杆菌使用O-抗原感测表面，以通过RcsF、UmoD/B蛋白和Rcs磷酸化介导启动信号转导级联，从而激活蜂群细胞分化。此外，Rcs调节子中编码细胞功能的基因 蜂群细胞分化所直接需要的蛋白质，如伸长和细胞分裂的抑制是未知的。 为了解决这一差距，RNA-Seq将用于识别由反应调节因子RcsB特异性调节的基因。