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: 8440574
• 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/8440574
• 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; 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，包括前列腺炎和感染性尿石，影响了我们的退伍军人人群中的很大一部分。这些感染使人衰弱，一旦建立可能很难治疗。革兰氏阴性细菌mirabilis是引起尿路感染的主要原因，尤其是在接受广泛导管插入术的患者中，例如老年疗养院患者和脊髓损伤的患者。当在固体表面（例如Foley导管或琼脂板）上生长时，Mirabilis会经历复杂的形态变化，其中细胞与典型的革兰氏阴性杆（营养细胞）区分为高度伸长的蜂窝细胞。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很重要。 Mirabilis识别表面并引发蜂群分化的机制在很大程度上是未知的。该提案将调查上一个融资期间确定的新型信号通路，该通路允许Mirabilis使用O-抗原通过RCSF，UMOD/B蛋白和RCS PhosphoreLay启动信号转导级联对表面进行启动。另外，编码细胞函数的RCS调节子中的基因 直接需要的蜂细胞分化所需的（例如伸长和抑制细胞分裂）尚不清楚。 为了解决这一差距，RNA-seq将用于识别由响应调节剂RCSB特别调节的基因。