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Cytochrome bd-I in Escherichia coli is less sensitive than cytochromes bd-II or bo′' to inhibition by the carbon monoxide-releasing molecule, CORM-3

Jesse, Helen E ; Nye, Tacita L ; Mclean, Samantha ; Green, Jeffrey ; Mann, Brian E ; Poole, Robert K

BBA - Proteins and Proteomics, September 2013, Vol.1834(9), pp.1693-1703 [Rivista Peer Reviewed]

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  • Titolo:
    Cytochrome bd-I in Escherichia coli is less sensitive than cytochromes bd-II or bo′' to inhibition by the carbon monoxide-releasing molecule, CORM-3
  • Autore: Jesse, Helen E ; Nye, Tacita L ; Mclean, Samantha ; Green, Jeffrey ; Mann, Brian E ; Poole, Robert K
  • Note di contenuto: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.bbapap.2013.04.019 Byline: Helen E. Jesse, Tacita L. Nye, Samantha McLean, Jeffrey Green, Brian E. Mann, Robert K. Poole Abstract: Background: CO-releasing molecules (CO-RMs) are potential therapeutic agents, able to deliver CO - a critical gasotransmitter - in biological environments. CO-RMs are also effective antimicrobial agents; although the mechanisms of action are poorly defined, haem-containing terminal oxidases are primary targets. Nevertheless, it is clear from several studies that the effects of CO-RMs on biological systems are frequently not adequately explained by the release of CO: CO-RMs are generally more potent inhibitors than is CO gas and other effects of the molecules are evident. Methods: Because sensitivity to CO-RMs cannot be predicted by sensitivity to CO gas, we assess the differential susceptibilities of strains, each expressing only one of the three terminal oxidases of E. coli -- cytochrome bd-I, cytochrome bd-II and cytochrome bo', to inhibition by CORM-3. We present the first sensitive measurement of the oxygen affinity of cytochrome bd-II (K.sub.m 0.24[mu]M) employing globin deoxygenation. Finally, we investigate the way(s) in which thiol compounds abolish the inhibitory effects of CORM-2 and CORM-3 on respiration, growth and viability, a phenomenon that is well documented, but poorly understood. Results: We show that a strain expressing cytochrome bd-I as the sole oxidase is least susceptible to inhibition by CORM-3 in its growth and respiration of both intact cells and membranes. Growth studies show that cytochrome bd-II has similar CORM-3 sensitivity to cytochrome bo'. Cytochromes bo' and bd-II also have considerably lower affinities for oxygen than bd-I. We show that the ability of N-acetylcysteine to abrogate the toxic effects of CO-RMs is not attributable to its antioxidant effects, or prevention of CO targeting to the oxidases, but may be largely due to the inhibition of CO-RM uptake by bacterial cells. Conclusions: A strain expressing cytochrome bd-I as the sole terminal oxidase is least susceptible to inhibition by CORM-3. N-acetylcysteine is a potent inhibitor of CO-RM uptake by E. coli. General significance: Rational design and exploitation of CO-RMs require a fundamental understanding of their activity. CO and CO-RMs have multifaceted effects on mammalian and microbial cells; here we show that the quinol oxidases of E. coli are differentially sensitive to CORM-3. This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins. Article History: Received 4 December 2012; Revised 18 April 2013; Accepted 19 April 2013 Article Note: (footnote) [star] This article is part of a Special Issue entitled: Oxygen Binding and Sensing Proteins., [star][star] This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
  • Fa parte di: BBA - Proteins and Proteomics, September 2013, Vol.1834(9), pp.1693-1703
  • Soggetti: Corm-3 ; Corm-2 ; Cytochrome ; Escherichia Coli ; Respiratory Oxidase ; N-Acetylcysteine ; Chemistry ; Anatomy & Physiology
  • Lingua: Inglese
  • Tipo: Articolo
  • Identificativo: ISSN: 1570-9639 ; E-ISSN: 1878-1454 ; DOI: 10.1016/j.bbapap.2013.04.019

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