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.
|Anderson, Sarah E; Sherman, Edgar X; Weiss, David S et al. (2018) Aminoglycoside Heteroresistance in Acinetobacter baumannii AB5075. mSphere 3:|
|Chin, Chui Yoke; Tipton, Kyle A; Farokhyfar, Marjan et al. (2018) A high-frequency phenotypic switch links bacterial virulence and environmental survival in Acinetobacter baumannii. Nat Microbiol 3:563-569|
|Tipton, Kyle A; Chin, Chui-Yoke; Farokhyfar, Marjan et al. (2018) Role of Capsule in Resistance to Disinfectants, Host Antimicrobials, and Desiccation in Acinetobacter baumannii. Antimicrob Agents Chemother 62:|
|Howery, Kristen E; Clemmer, Katy M; ?im?ek, Emrah et al. (2015) Regulation of the Min Cell Division Inhibition Complex by the Rcs Phosphorelay in Proteus mirabilis. J Bacteriol 197:2499-507|
|Szostek, Bree A; Rather, Philip N (2013) Regulation of the swarming inhibitor disA in Proteus mirabilis. J Bacteriol 195:3237-43|
|Kurihara, Shin; Sakai, Yumi; Suzuki, Hideyuki et al. (2013) Putrescine importer PlaP contributes to swarming motility and urothelial cell invasion in Proteus mirabilis. J Biol Chem 288:15668-76|
|Stevenson, Lindsay G; Szostek, Bree A; Clemmer, Katy M et al. (2013) Expression of the DisA amino acid decarboxylase from Proteus mirabilis inhibits motility and class 2 flagellar gene expression in Escherichia coli. Res Microbiol 164:31-7|
|Morgenstein, Randy M; Rather, Philip N (2012) Role of the Umo proteins and the Rcs phosphorelay in the swarming motility of the wild type and an O-antigen (waaL) mutant of Proteus mirabilis. J Bacteriol 194:669-76|