Differential antibacterial activity against Pseudomonas aeruginosa by carbon monoxide-releasing molecules. - Archive ouverte HAL Access content directly
Journal Articles Antioxidants and Redox Signaling Year : 2012

Differential antibacterial activity against Pseudomonas aeruginosa by carbon monoxide-releasing molecules.

(1, 2) , (3) , (2) , (2) , (2) , (4) , (5) , (5) , (5) , (1) , (2, 6) , (2, 7)
1
2
3
4
5
6
7

Abstract

AIMS: Carbon monoxide (CO) delivered in a controlled manner to cells and organisms mediates a variety of pharmacological effects to the extent that CO-releasing molecules (CO-RMs) are being developed for therapeutic purposes. Recently, ruthenium-based CO-RMs have been shown to posses important bactericidal activity. Here we assessed the effect of fast CO releasers containing ruthenium (Ru(CO)(3)Cl(glycinate) [CORM-3] and tricarbonyldichlororuthenium(II) dimer [CORM-2]) and a novel slow manganese-based CO releaser ([Me(4)N][Mn(CO)(4)(thioacetate)(2)] [CORM-371]) on O(2) consumption and growth of Pseudomonas aeruginosa (PAO1). We then compared these effects with the action elicited by sodium boranocarbonate (CORM-A1), which lacks a transition metal but liberates CO with a rate similar to CORM-371. RESULTS: CORM-2, CORM-3, and, to a lesser extent, CORM-371 exerted a significant bactericidal effect and decreased O(2) consumption in PAO1 in vitro. The effect appeared to be independent of reactive oxygen species production, but in the case of metal-containing compounds it was prevented by the thiol donor N-acetylcysteine. In contrast, CORM-A1 was bacteriostatic rather than bactericidal in vitro eliciting only a moderate and transient decrease in O(2) consumption. INNOVATION: None of the tested CO-RMs was toxic to murine macrophages or human fibroblasts at the concentration impairing PA01 growth but only ruthenium-containing CO-RMs showed potential therapeutic properties by increasing the survival of mice infected with PA01. CONCLUSION: CO carriers inhibit bacterial growth and O(2) consumption in vitro, but transition metal carbonyls appear more powerful than compounds spontaneously liberating CO. The nature of the metal in CO-RMs also modulates the anti-bacterial effect, with ruthenium-based CO-RMs being efficacious both in vitro and in vivo.
Fichier principal
Vignette du fichier
ars.2011.pdf (1.38 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Loading...

Dates and versions

inserm-00656413 , version 1 (04-01-2012)

Identifiers

Cite

Mathieu Desmard, Roberta Foresti, Didier Morin, Maylis Dagoussat, Alain Berdeaux, et al.. Differential antibacterial activity against Pseudomonas aeruginosa by carbon monoxide-releasing molecules.. Antioxidants and Redox Signaling, 2012, 16 (2), pp.153-63. ⟨10.1089/ars.2011.3959⟩. ⟨inserm-00656413⟩
159 View
510 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More