title: Effect of cyclic bis(3'-5')diguanylic acid and its analogs on bacterial biofilm formation.
abstract: Cyclic bis(3'-5')diguanylic acid (cyclic-di-GMP) functions as a second messenger in diverse species of bacteria to trigger wide-ranging physiological changes. We measured cyclic-di-GMP and its structural analogs such as cyclic bis(3'-5')guanylic/adenylic acid (cyclic-GpAp), cyclic bis(3'-5')guanylic/inosinic acid (cyclic-GpIp) and monophosphorothioic acid of cyclic-di-GMP (cyclic-GpGps) for effects on the biofilm formation of Staphylococcus aureus and Pseudomonas aeruginosa. We constructed a knockout mutant of SA0701, which is a GGDEF motif protein relevant to diguanylate cyclase from S. aureus 2507. We confirmed that the biofilm formation of this mutant (MS2507 Delta SA0701) was reduced. Cyclic-di-GMP corresponding to physiological intracellular levels given in the culture recovered the biofilm formation of MS2507 Delta SA0701, whereas its analogs did not, indicating that unlike a previous suggestion, cyclic-di-GMP was involved in the positive regulation of the biofilm formation of S. aureus and its action was structurally specific. At a high concentration (200 microM), cyclic-di-GMP and its analogs showed suppression effects on the biofilm formation of S. aureus and P. aeruginosa, and according to the quantification study using costat analysis, the suppression potential was in the order of cyclic-di-GMP, cyclic-GpGps, cyclic-GpAp and cyclic-GpIp, suggesting that the suppression effect was not strictly specific and the change of base structure quantitatively affected the suppression activity.
authors.affiliation: Department of Bacteriology, Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Ishihara
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hyodo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: Taichi
authors.initials: T
authors.lastname: Kamegaya
authors.forename: Keiko
authors.initials: K
authors.lastname: Yamada
authors.forename: Akira
authors.initials: A
authors.lastname: Okamoto
authors.forename: Tadao
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Michio
authors.initials: M
authors.lastname: Ohta
mesh_terms: D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D018533:Biomass; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D055786:Gene Knockout Techniques; D006133:Growth Substances / Q000494:pharmacology*; D015394:Molecular Structure; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000254:growth & development*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development*
chemical_list: D006133:Growth Substances; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP