Bis-(3' -5' ) cyclic dimeric guanosine monophosphate (c-di-GMP) controls the lifestyle transition between the sessile and motile state in many Gram-negative bacteria, including the opportunistic human pathogen Pseudomonas aeruginosa. Under laboratory conditions, high concentrations of c-di-GMP decrease motility and promote biofilm formation while low concentrations of c-di-GMP promote motility and decease biofilm formation. Here we seek to determine the contribution of c-di-GMP signaling to biofilm formation during P. aeruginosa mediated catheter-associated urinary tract infection (CAUTI). Using a murine CAUTI model, a decrease in colony forming units (CFUs) was detected in the bladder and kidneys of mice infected with strains overexpressing the phosphodiesterases (PDEs) PA3947 and PA2133 compared to wild-type P. aeruginosa. Conversely, overexpression of the diguanylate cyclases (DGCs) PA3702 and PA1107 increased the number of bacteria in bladder and significantly increased dissemination of bacteria to the kidneys compared to wild type.

 

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