title: The diguanylate cyclase SadC is a central player in Gac/Rsm-mediated biofilm formation in Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa is a Gram-negative opportunistic human pathogen and a threat for immunocompromised and cystic fibrosis patients. It is responsible for acute and chronic infections and can switch between these lifestyles upon taking an informed decision involving complex regulatory networks. The RetS/LadS/Gac/Rsm network and the cyclic-di-GMP (c-di-GMP) signaling pathways are both central to this phenomenon redirecting the P. aeruginosa population toward a biofilm mode of growth, which is associated with chronic infections. While these two pathways were traditionally studied independently from each other, we recently showed that cellular levels of c-di-GMP are increased in the hyperbiofilm retS mutant. Here, we have formally established the link between the two networks by showing that the SadC diguanylate cyclase is central to the Gac/Rsm-associated phenotypes, notably, biofilm formation. Importantly, SadC is involved in the signaling that converges onto the RsmA translational repressor either via RetS/LadS or via HptB/HsbR. Although the level of expression of the sadC gene does not seem to be impacted by the regulatory cascade, the production of the SadC protein is tightly repressed by RsmA. This adds to the growing complexity of the signaling network associated with c-di-GMP in P. aeruginosa. While this organism possesses more than 40 c-di-GMP-related enzymes, it remains unclear how signaling specificity is maintained within the c-di-GMP network. The finding that SadC but no other diguanylate cyclase is related to the formation of biofilm governed by the Gac/Rsm pathway further contributes to understanding of this insulation mechanism.
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London, United Kingdom.
authors.forename: Joana A
authors.initials: JA
authors.lastname: Moscoso
authors.affiliation: Biozentrum of the University of Basel, Basel, Switzerland.
authors.forename: Tina
authors.initials: T
authors.lastname: Jaeger
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London, United Kingdom.
authors.forename: Martina
authors.initials: M
authors.lastname: Valentini
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London, United Kingdom.
authors.forename: Kailyn
authors.initials: K
authors.lastname: Hui
authors.affiliation: Biozentrum of the University of Basel, Basel, Switzerland.
authors.forename: Urs
authors.initials: U
authors.lastname: Jenal
authors.affiliation: MRC Centre for Molecular Bacteriology and Infection, Department of Life Sciences, Imperial College London, London, United Kingdom a.filloux@imperial.ac.uk.
authors.forename: Alain
authors.initials: A
authors.lastname: Filloux
mesh_terms: D018441:Biofilms / Q000254:growth & development*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D019761:Phosphorus-Oxygen Lyases / Q000235:genetics / Q000378:metabolism*; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000502:physiology*; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D029968:Escherichia coli Proteins; D012097:Repressor Proteins; C062025:bis(3',5')-cyclic diguanylic acid; D019761:Phosphorus-Oxygen Lyases; C060720:diguanylate cyclase; D006152:Cyclic GMP