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During urinary tract infections (UTIs), uropathogenicEscherichia coli must maintain a delicate balance between sessility and motility to achieve successful infection of both the bladder and kidneys. Previous studies showed that cyclic dimeric GMP (c-di-GMP) levels aid in the control of the transition between motile and nonmotile states inE. coli . TheyfiRNB locus inE. coli CFT073 contains genes for YfiN, a diguanylate cyclase, and its activity regulators, YfiR and YfiB. Deletion ofyfiR yielded a mutant that was attenuated in both the bladder and the kidneys when tested in competition with the wild-type strain in the murine model of UTI. A doubleyfiRN mutant was not attenuated in the mouse model, suggesting that unregulated YfiN activity and likely increased cytoplasmic c-di-GMP levels cause a survival defect. Curli fimbriae and cellulose production were increased in theyfiR mutant. Expression ofyhjH , a gene encoding a proven phosphodiesterase, in CFT073 ΔyfiR suppressed the overproduction of curli fimbriae and cellulose and further verified that deletion ofyfiR results in c-di-GMP accumulation. Additional deletion ofcsgD andbcsA , genes necessary for curli fimbriae and cellulose production, respectively, returned colonization levels of theyfiR deletion mutant to wild-type levels. Peroxide sensitivity assays and iron acquisition assays displayed no significant differences between theyfiR mutant and the wild-type strain. These results indicate that dysregulation of c-di-GMP production results in pleiotropic effects that disableE. coli in the urinary tract and implicate the c-di-GMP regulatory system as an important factor in the persistence of uropathogenicE. coli in vivo .

infection and immunity

Genetic Analysis of the Role of <i>yfiR</i> in the Ability of Escherichia coli CFT073 To Control Cellular Cyclic Dimeric GMP Levels and To Persist in the Urinary Tract

Genetic Analysis of the Role of yfiR in the Ability of Escherichia coli CFT073 To Control Cellular Cyclic Dimeric GMP Levels and To Persist in the Urinary Tract