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Tags
HERO ID
2278749
Reference Type
Journal Article
Title
Analysis of the Bacterial Response to Ru(CO)(3)Cl(Glycinate) (CORM-3) and the Inactivated Compound Identifies the Role Played by the Ruthenium Compound and Reveals Sulfur-Containing Species as a Major Target of CORM-3 Action
Author(s)
Mclean, S; Begg, R; Jesse, HE; Mann, BE; Sanguinetti, G; Poole, RK
Year
2013
Is Peer Reviewed?
Yes
Journal
Antioxidants & Redox Signaling
ISSN:
1523-0864
EISSN:
1557-7716
Volume
19
Issue
17
Page Numbers
1999-2012
Language
English
PMID
23472713
DOI
10.1089/ars.2012.5103
Web of Science Id
WOS:000328557000002
Abstract
Aims: Carbon monoxide (CO)-releasing molecules (CO-RMs) are being developed with the ultimate goal of safely utilizing the therapeutic potential of CO clinically. One such application is antimicrobial activity; therefore, we aimed to characterize and compare the effects of the CO-RM, CORM-3, and its inactivated counterpart, where all labile CO has been removed, at the transcriptomic and cellular level. Results: We found that both compounds are able to penetrate the cell, but the inactive form is not inhibitory to bacterial growth under conditions where CORM-3 is. Transcriptomic analyses revealed that the bacterial response to inactivated CORM-3 (iCORM-3) is much lower than to the active compound and that a wide range of processes appear to be affected by CORM-3 and to a lesser extent iCORM-3, including energy metabolism, membrane transport, motility, and the metabolism of many sulfur-containing species, including cysteine and methionine. Innovation: This work has demonstrated that both CORM-3 and its inactivated counterpart react with cellular functions to yield a complex response at the transcriptomic level. A full understanding of the actions of both compounds is vital to understand the toxic effects of CO-RMs. Conclusion: This work has furthered our understanding of how CORM-3 behaves at the cellular level and identifies the responses that occur when the host is exposed to the Ru compound as well as those that result from the released CO. This is a vital step in laying the groundwork for future development of optimized CO-RMs for eventual use in antimicrobial therapy. Antioxid. Redox Signal. 19, 1999-2012.
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