Effect of cyclic bis(3′–5′)diguanylic acid and its analogs on bacterial biofilm formation

• Published in: FEMS microbiology letters Vol. 301; no. 2; pp. 193 - 200
• Main Authors: Ishihara, Yuka, Hyodo, Mamoru, Hayakawa, Yoshihiro, Kamegaya, Taichi, Yamada, Keiko, Okamoto, Akira, Hasegawa, Tadao, Ohta, Michio
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.12.2009; Wiley-Blackwell; Oxford University Press
• Subjects: Acids; Analogs; Bacteriology; biofilm; Biofilms; Biofilms - drug effects; Biofilms - growth & development; Biological and medical sciences; Biomass; Cost analysis; Cyclic GMP - analogs & derivatives; Cyclic GMP - pharmacology; cyclic‐di‐GMP; Fundamental and applied biological sciences. Psychology; GdpS; Gene Knockout Techniques; Growth Substances - pharmacology; Intracellular levels; Microbiology; Miscellaneous; Molecular Structure; Pathogens; Physiology; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - growth & development; regulation of biofilm formation; Research Letters; Species diversity; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - growth & development; GdpS; cyclic-di-GMP; regulation of biofilm formation; biofilm; Pseudomonadales; biofilrn; GMP; Biofilm; Bacteria; Micrococcales; Pseudomonadaceae; Pseudomonas aeruginosa; Micrococcaceae; Staphylococcus aureus
• ISSN: 0378-1097; 1574-6968
• DOI: 10.1111/j.1574-6968.2009.01825.x

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 (MS2507ΔSA0701) was reduced. Cyclic-di-GMP corresponding to physiological intracellular levels given in the culture recovered the biofilm formation of MS2507ΔSA0701, 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 μM), 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.