Altered Regulation of the Diguanylate Cyclase YaiC Reduces Production of Type 1 Fimbriae in a Pst Mutant of Uropathogenic Escherichia coli CFT073.

The gene cluster encodes the phosphate-specific transport (Pst) system. Inactivation of the Pst system constitutively activates the two-component regulatory system PhoBR and attenuates the virulence of pathogenic bacteria. In uropathogenic strain CFT073, attenuation by inactivation of is predominantly attributed to the decreased expression of type 1 fimbriae. However, the molecular mechanisms connecting the Pst system and type 1 fimbriae are unknown. To address this, a transposon library was constructed in the mutant, and clones were tested for a regain in type 1 fimbrial production. Among them, the diguanylate cyclase encoded by ( in ) was identified to connect the Pst system and type 1 fimbrial expression. In the mutant, the decreased expression of type 1 fimbriae is connected by the induction of This is predominantly due to altered expression of the FimBE-like recombinase genes and , affecting at the same time the inversion of the promoter switch (). In the mutant, inactivation of restored -dependent adhesion to bladder cells and virulence. Interestingly, the expression of was activated by PhoB, since transcription of was linked to the PhoB-dependent operon. As YaiC is involved in cyclic di-GMP (c-di-GMP) biosynthesis, an increased accumulation of c-di-GMP was observed in the mutant. Hence, the results suggest that one mechanism by which deletion of the Pst system reduces the expression of type 1 fimbriae is through PhoBR-mediated activation of , which in turn increases the accumulation of c-di-GMP, represses the operon, and, consequently, attenuates virulence in the mouse urinary tract infection model. Urinary tract infections (UTIs) are common bacterial infections in humans. They are mainly caused by uropathogenic (UPEC). We previously showed that interference with phosphate homeostasis decreases the expression of type 1 fimbriae and attenuates UPEC virulence. Herein, we identified that alteration of the phosphate metabolism increases production of the signaling molecule c-di-GMP, which in turn decreases the expression of type 1 fimbriae. We also determine the regulatory cascade leading to the accumulation of c-di-GMP and identify the Pho regulon as new players in c-di-GMP-mediated cell signaling. By understanding the molecular mechanisms leading to the expression of virulence factors, we will be in a better position to develop new therapeutics.