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.
Urinary-tract infections are the most common of all hospital-acquired infections and prolong hospitalization an average of 3.5 days. The use of indwelling Foley catheters to manage urinary incontinence is responsible for 40% of urinary-tract infections. The Gram-negative bacterium Proteus mirabilis is a leading cause of urinary-tract infections in patients undergoing long-term catheterization. During growth on solid surfaces, 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. Understanding the molecular basis of this differentiation could lead to strategies aimed at preventing this process.
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