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A carbon monoxide‐releasing molecule (CORM‐3) exerts bactericidal activity against Pseudomonas aeruginosa and improves survival in an animal model of bacteraemia
Author(s) -
Desmard Mathieu,
Davidge Kelly S.,
Bouvet Odile,
Morin Didier,
Roux Damien,
Foresti Roberta,
Ricard Jean D.,
Denamur Erick,
Poole Robert K.,
Montravers Philippe,
Morterlini Roberto,
Boczkowski Jorge
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-122804
Subject(s) - pseudomonas aeruginosa , antibiotics , microbiology and biotechnology , chemistry , antimicrobial , bacteria , antibacterial activity , in vitro , corm , pharmacology , biology , biochemistry , genetics , agronomy
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 50fold 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.—Desmard, M., Davidge, K. S., Bouvet, O., Morin, D., Roux, D., Foresti, R., Ricard, J. D., Denamur, E., Poole, R. K., Montravers, P., Motterlini, R., Boczkowski, J. A carbon monoxide‐releasing molecule (CORM‐3) exerts bactericidal activity against Pseudomonas aeruginosa and improves survival in an animal model of bacteraemia. FASEB J . 23, 1023–1031 (2009)