title: A carbon monoxide-releasing molecule (CORM-3) exerts bactericidal activity against Pseudomonas aeruginosa and improves survival in an animal model of bacteraemia.
abstract: The search for new molecules to fight Pseudomonas aeruginosa is of paramount importance. Carbon monoxide (CO) is known to act as an effective inhibitor of the respiratory chain in P. aeruginosa, but the practical use of this gas as an antibacterial molecule is hampered by its toxicity and difficulty to manipulate. Here, we show that a water-soluble CO releaser (CORM-3) possesses bactericidal properties against laboratory and antibiotic-resistant P. aeruginosa. CORM-3 reduced the bacterial count by 4 logs 180 min after in vitro treatment. CORM-3-treated bacteria had a lower O(2) consumption than vehicle-treated bacteria, and the decrease in O(2) consumption temporally preceded the bactericidal action of CORM-3. These results support the hypothesis that the antimicrobial effect of CORM-3 is mediated by an interaction of CO liberated by the carrier with the bacterial respiratory chain. The antibacterial effect occurred at concentrations of CORM-3 that are 50-fold lower than toxic concentrations for eukaryotic cells. CORM-3 treatment compared to vehicle treatment decreased bacterial counts in the spleen and increased survival in immunocompetent and immunosuppressed mice following P. aeruginosa bacteremia. Our results suggest that CORMs could form the basis for developing a new therapeutic strategy against P. aeruginosa-induced infection.
authors.affiliation: Inserm U700, Faculté de Médecine, Université Paris 7, Paris, France. desmardmathieu@yahoo.fr
authors.forename: Mathieu
authors.initials: M
authors.lastname: Desmard
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Davidge
authors.forename: Odile
authors.initials: O
authors.lastname: Bouvet
authors.forename: Didier
authors.initials: D
authors.lastname: Morin
authors.forename: Damien
authors.initials: D
authors.lastname: Roux
authors.forename: Roberta
authors.initials: R
authors.lastname: Foresti
authors.forename: Jean D
authors.initials: JD
authors.lastname: Ricard
authors.forename: Erick
authors.initials: E
authors.lastname: Denamur
authors.forename: Robert K
authors.initials: RK
authors.lastname: Poole
authors.forename: Philippe
authors.initials: P
authors.lastname: Montravers
authors.forename: Roberto
authors.initials: R
authors.lastname: Motterlini
authors.forename: Jorge
authors.initials: J
authors.lastname: Boczkowski
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016470:Bacteremia; D002460:Cell Line; D002470:Cell Survival; D015169:Colony Count, Microbial / Q000379:methods; D004305:Dose-Response Relationship, Drug; D051379:Mice; D023421:Models, Animal; D009942:Organometallic Compounds / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development*; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents; D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II)