Wilson, J.L, Jesse, H.E, Hughes, B et al. (6 more authors) (2013) Ru(CO)(3)Cl(Glycinate) (CORM-3): A Carbon Monoxide-Releasing Molecule with Broad-Spectrum Antimicrobial and Photosensitive Activities Against Respiration and Cation Transport in Escherichia coli. Antioxidants and Redox Signaling, 19 (5). 497 - 509. ISSN 1523-0864
Abstract
Aims: Carbon monoxide (CO) delivered to cells and tissues by CO-releasing molecules (CO-RMs) has beneficial and toxic effects not mimicked by CO gas. The metal carbonyl Ru(CO)3Cl(glycinate) (CORM-3) is a novel, potent antimicrobial agent. Here, we established its mode of action. Results: CORM-3 inhibits respiration in several bacterial and yeast pathogens. In anoxic Escherichia coli suspensions, CORM-3 first stimulates, then inhibits respiration, but much higher concentrations of CORM-3 than of a classic protonophore are required for stimulation. Proton translocation measurements (H+/O quotients, i.e., H+ extrusion on pulsing anaerobic cells with O2) show that respiratory stimulation cannot be attributed to true ‘‘uncoupling,’’ that is, dissipation of the protonmotive force, or to direct stimulation of oxidase activity. Our data are consistent with CORM-3 facilitating the electrogenic transmembrane movement of K+ (or Na+), causing a stimulation of respiration and H+ pumping to compensate for the transient drop in membrane potential (DJ). The effects on respiration are not mimicked by CO gas or control Ru compounds that do not release CO. Inhibition of respiration and loss of bacterial viability elicited by CORM-3 are reversible by white light, unambiguously identifying heme-containing oxidase(s) as target(s). Innovation: This is the most complete study to date of the antimicrobial action of a CO-RM. Noteworthy are the demonstration of respiratory stimulation, electrogenic ion transport, and photosensitive activity, establishing terminal oxidases and ion transport as primary targets. Conclusion: CORM-3 has multifaceted effects: increased membrane permeability, inhibition of terminal oxidases, and perhaps other unidentified mechanisms underlie its effectiveness in tackling microbial pathogenesis.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2013 The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution Licence (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Funding Information: | Funder Grant number BBSRC BB/H016805/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 07 May 2014 14:04 |
Last Modified: | 07 May 2014 14:04 |
Published Version: | http://dx.doi.org/10.1089/ars.2012.4784 |
Status: | Published |
Publisher: | Mary Ann Liebert |
Refereed: | Yes |
Identification Number: | 10.1089/ars.2012.4784 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:78847 |