High levels of cAMP inhibit Pseudomonas aeruginosa biofilm formation through reduction of the c-di-GMP content

• Published in: Microbiology (Society for General Microbiology) 2019-03, Vol.165 (3), p.324-333
• Main Authors: Almblad, Henrik, Rybtke, Morten, Hendiani, Saghar, Andersen, Jens Bo, Givskov, Michael, Tolker-Nielsen, Tim
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Biofilms - growth & development; Cyclic AMP - metabolism; Cyclic AMP Receptor Protein - genetics; Cyclic AMP Receptor Protein - metabolism; Cyclic GMP - analogs & derivatives; Cyclic GMP - metabolism; Extracellular Polymeric Substance Matrix - metabolism; Mutation; Phosphoric Diester Hydrolases - genetics; Phosphoric Diester Hydrolases - metabolism; Pseudomonas aeruginosa - genetics; Pseudomonas aeruginosa - growth & development; Pseudomonas aeruginosa - metabolism; Pseudomonas aeruginosa - physiology
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/mic.0.000772

The human pathogen Pseudomonas aeruginosa can cause both acute infections and chronic biofilm-based infections. Expression of acute virulence factors is positively regulated by cAMP, whereas biofilm formation is positively regulated by c-di-GMP. We provide evidence that increased levels of cAMP, caused by either a lack of degradation or increased production, inhibit P. aeruginosa biofilm formation. cAMP-mediated inhibition of P. aeruginosa biofilm formation required Vfr, and involved a reduction of the level of c-di-GMP, as well as reduced production of biofilm matrix components. A mutant screen and characterization of defined knockout mutants suggested that a subset of c-di-GMP-degrading phosphodiesterases is involved in cAMP-Vfr-mediated biofilm inhibition in P. aeruginosa.