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Inactivation of the Pst system constitutively activates the two-component regulatory system PhoBR and attenuates the virulence of pathogenic bacteria. In uropathogenic<jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>strain CFT073, attenuation by inactivation of<jats:italic>pst<\/jats:italic>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<jats:italic>pst<\/jats:italic>mutant, and clones were tested for a regain in type 1 fimbrial production. Among them, the diguanylate cyclase encoded by<jats:italic>yaiC<\/jats:italic>(<jats:italic>adrA<\/jats:italic>in<jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>) was identified to connect the Pst system and type 1 fimbrial expression. In the<jats:italic>pst<\/jats:italic>mutant, the decreased expression of type 1 fimbriae is connected by the induction of<jats:italic>yaiC<\/jats:italic>. This is predominantly due to altered expression of the FimBE-like recombinase genes<jats:italic>ipuA<\/jats:italic>and<jats:italic>ipbA<\/jats:italic>, affecting at the same time the inversion of the<jats:italic>fim<\/jats:italic>promoter switch (<jats:italic>fimS<\/jats:italic>). In the<jats:italic>pst<\/jats:italic>mutant, inactivation of<jats:italic>yaiC<\/jats:italic>restored<jats:italic>fim<\/jats:italic>-dependent adhesion to bladder cells and virulence. Interestingly, the expression of<jats:italic>yaiC<\/jats:italic>was activated by PhoB, since transcription of<jats:italic>yaiC<\/jats:italic>was linked to the PhoB-dependent<jats:italic>phoA-psiF<\/jats:italic>operon. As YaiC is involved in cyclic di-GMP (c-di-GMP) biosynthesis, an increased accumulation of c-di-GMP was observed in the<jats:italic>pst<\/jats:italic>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<jats:italic>yaiC<\/jats:italic>, which in turn increases the accumulation of c-di-GMP, represses the<jats:italic>fim<\/jats:italic>operon, and, consequently, attenuates virulence in the mouse urinary tract infection model.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Urinary tract infections (UTIs) are common bacterial infections in humans. They are mainly caused by uropathogenic<jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>(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.<\/jats:p>","DOI":"10.1128\/jb.00168-17","type":"journal-article","created":{"date-parts":[[2017,9,19]],"date-time":"2017-09-19T00:40:15Z","timestamp":1505781615000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Altered Regulation of the Diguanylate Cyclase YaiC Reduces Production of Type 1 Fimbriae in a Pst Mutant of Uropathogenic Escherichia coli CFT073"],"prefix":"10.1128","volume":"199","author":[{"given":"S\u00e9bastien","family":"Cr\u00e9pin","sequence":"first","affiliation":[{"name":"INRS-Institut Armand-Frappier, Laval, Qu\u00e9bec, Canada"},{"name":"Centre de Recherche en Infectiologie Porcine et Avicole (CRIPA), Universit\u00e9 de Montr\u00e9al, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Saint-Hyacinthe, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ga\u00eblle","family":"Porcheron","sequence":"additional","affiliation":[{"name":"INRS-Institut Armand-Frappier, Laval, Qu\u00e9bec, Canada"},{"name":"Centre de Recherche en Infectiologie Porcine et Avicole (CRIPA), Universit\u00e9 de Montr\u00e9al, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Saint-Hyacinthe, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Houle","sequence":"additional","affiliation":[{"name":"INRS-Institut Armand-Frappier, Laval, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9e","family":"Harel","sequence":"additional","affiliation":[{"name":"Centre de Recherche en Infectiologie Porcine et Avicole (CRIPA), Universit\u00e9 de Montr\u00e9al, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Saint-Hyacinthe, Qu\u00e9bec, Canada"},{"name":"Groupe de Recherche sur les Maladies Infectieuses du Porc (GREMIP), Universit\u00e9 de Montr\u00e9al, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Saint-Hyacinthe, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles M.","family":"Dozois","sequence":"additional","affiliation":[{"name":"INRS-Institut Armand-Frappier, Laval, Qu\u00e9bec, Canada"},{"name":"Centre de Recherche en Infectiologie Porcine et Avicole (CRIPA), Universit\u00e9 de Montr\u00e9al, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Saint-Hyacinthe, Qu\u00e9bec, Canada"},{"name":"Groupe de Recherche sur les Maladies Infectieuses du Porc (GREMIP), Universit\u00e9 de Montr\u00e9al, Facult\u00e9 de M\u00e9decine V\u00e9t\u00e9rinaire, Saint-Hyacinthe, Qu\u00e9bec, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0004(01)01852-7"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2010.01.014"},{"key":"e_1_3_3_4_2","first-page":"1357","volume-title":"Escherichia coli and Salmonella: cellular and molecular biology","author":"Wanner BL","year":"1996","unstructured":"Wanner BL . 1996. 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