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

Autor: Sébastien Houle, Charles M. Dozois, Gaëlle Porcheron, Sébastien Crépin, Josée Harel
Přispěvatelé: Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Université de Montréal (UdeM), S.C. was supported by scholarships from the Fonds Québécois de la Recherche sur la Nature et les Technologies (FQRNT), the Fondation Armand-Frappier and the Centre de Recherche en Infectiologie Porcine (CRIP). G.P. was supported by scholarship from the Fondation Armand-Frappier. This work was supported by a Canada Research Chair (2009-2014) and from the Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grants (RGPIN 250129-07 and 2014-06622) to C.M.D. and by an NSERC Discovery grant (RGPIN-2015-05373) to J.H.
Rok vydání: 2017
Předmět:
0301 basic medicine
Operon
[SDV]Life Sciences [q-bio]
Fimbria
Mutant
MESH: Escherichia coli Proteins
MESH: Urinary Tract Infections
MESH: Virulence
medicine.disease_cause
MESH: Recombinases
Mice
MESH: Urinary Bladder
Recombinase
Uropathogenic Escherichia coli
MESH: Cyclic GMP
MESH: Animals
Cyclic GMP
Escherichia coli Infections
MESH: Gene Expression Regulation
Bacterial
Virulence
Escherichia coli Proteins
MESH: Phosphorus-Oxygen Lyases
food and beverages
c-di-GMP
MESH: Transcription Factors
type 1 fimbriae
Multigene Family
Urinary Tract Infections
MESH: Phosphates
MESH: Regulon
MESH: ATP-Binding Cassette Transporters
Phosphorus-Oxygen Lyases
Research Article
MESH: Operon
MESH: Mutation
Urinary Bladder
030106 microbiology
Biology
Regulon
pst
Microbiology
Phosphates
Pho regulon
MESH: Fimbriae
Bacterial
Recombinases
03 medical and health sciences
Escherichia coli
medicine
Animals
Humans
MESH: Mice
Molecular Biology
phosphate
MESH: Escherichia coli Infections
MESH: Humans
fungi
Gene Expression Regulation
Bacterial
Fimbriae
Bacterial
Mutation
MESH: Uropathogenic Escherichia coli
biology.protein
bacteria
MESH: Multigene Family
ATP-Binding Cassette Transporters
Diguanylate cyclase
UPEC
urinary tract infection
Transcription Factors
Zdroj: Journal of Bacteriology
Journal of Bacteriology, American Society for Microbiology, 2017, 199 (24), pp.e00168-17. ⟨10.1128/JB.00168-17⟩
ISSN: 1098-5530
0021-9193
Popis: The pst 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 Escherichia coli strain CFT073, attenuation by inactivation of pst 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 pst mutant, and clones were tested for a regain in type 1 fimbrial production. Among them, the diguanylate cyclase encoded by yaiC ( adrA in Salmonella ) was identified to connect the Pst system and type 1 fimbrial expression. In the pst mutant, the decreased expression of type 1 fimbriae is connected by the induction of yaiC . This is predominantly due to altered expression of the FimBE-like recombinase genes ipuA and ipbA , affecting at the same time the inversion of the fim promoter switch ( fimS ). In the pst mutant, inactivation of yaiC restored fim -dependent adhesion to bladder cells and virulence. Interestingly, the expression of yaiC was activated by PhoB, since transcription of yaiC was linked to the PhoB-dependent phoA-psiF operon. As YaiC is involved in cyclic di-GMP (c-di-GMP) biosynthesis, an increased accumulation of c-di-GMP was observed in the pst 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 yaiC , which in turn increases the accumulation of c-di-GMP, represses the fim operon, and, consequently, attenuates virulence in the mouse urinary tract infection model. IMPORTANCE Urinary tract infections (UTIs) are common bacterial infections in humans. They are mainly caused by uropathogenic Escherichia coli (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.
Databáze: OpenAIRE
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