title: 3',5'-cyclic diguanylic acid reduces the virulence of biofilm-forming Staphylococcus aureus strains in a mouse model of mastitis infection.
abstract: The cyclic dinucleotide 3',5'-cyclic diguanylic acid (c-di-GMP) is a naturally occurring small molecule that regulates important signaling systems in bacteria. We have recently shown that c-di-GMP inhibits Staphylococcus aureus biofilm formation in vitro and its adherence to HeLa cells. We now report that c-di-GMP treatment has an antimicrobial and antipathogenic activity in vivo and reduces, in a dose-dependent manner, bacterial colonization by biofilm-forming S. aureus strains in a mouse model of mastitis infection. Intramammary injections of 5 and 50 nmol of c-di-GMP decreased colonization (bacterial CFU per gram of gland) by 0.79 (P > 0.05) and 1.44 (P < 0.01) logs, respectively, whereas 200-nmol doses allowed clearance of the bacteria below the detection limit with a reduction of more than 4 logs (P < 0.001) compared to the untreated control groups. These results indicate that cyclic dinucleotides potentially represent an attractive and novel drug platform which could be used alone or in combination with other agents or drugs in the prevention, treatment, or control of infection.
authors.affiliation: CEVDM, Département de biologie, Faculté des sciences, Université de Sherbrooke, 2500 Boul. Université, Sherbrooke, Québec, Canada.
authors.forename: Eric
authors.initials: E
authors.lastname: Brouillette
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hyodo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Hayakawa
authors.forename: David K R
authors.initials: DK
authors.lastname: Karaolis
authors.forename: François
authors.initials: F
authors.lastname: Malouin
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002417:Cattle; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D008414:Mastitis, Bovine / Q000188:drug therapy* / Q000382:microbiology / Q000503:physiopathology; D051379:Mice; D023421:Models, Animal; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; C062025:bis(3',5')-cyclic diguanylic acid; D006152:Cyclic GMP