REVIEW: Cytochrome bd Protects Bacteria against Oxidative and Nitrosative Stress: A Potential Target for Next-Generation Antimicrobial Agents

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V. B. Borisov^1*, E. Forte², S. A. Siletsky¹, M. Arese², A. I. Davletshin^1,3, P. Sarti^2,4, and A. Giuffrè⁴

¹Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, 119991 Moscow, Russia; fax: (495) 939-3181; E-mail: bor@genebee.msu.su

²Department of Biochemical Sciences and Istituto Pasteur – Fondazione Cenci Bolognetti, Sapienza University of Rome, I-00185 Rome, Italy

³Institute of Oriental and Classical Studies, Russian State University for the Humanities, 125993 Moscow, Russia

⁴CNR Institute of Molecular Biology and Pathology, I-00185 Rome, Italy

^* To whom correspondence should be addressed.

Received December 22, 2014; Revision received January 23, 2015

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Cytochrome bd is a terminal quinol oxidase of the bacterial respiratory chain. This tri-heme integral membrane protein generates a proton motive force at lower efficiency than heme-copper oxidases. This notwithstanding, under unfavorable growth conditions bacteria often use cytochrome bd in place of heme-copper enzymes as the main terminal oxidase. This is the case for several pathogenic and opportunistic bacteria during host colonization. This review summarizes recent data on the contribution of cytochrome bd to bacterial resistance to hydrogen peroxide, nitric oxide, and peroxynitrite, harmful species produced by the host as part of the immune response to microbial infections. Growing evidence supports the hypothesis that bd-type oxidases contribute to bacterial virulence by promoting microbial survival under oxidative and nitrosative stress conditions. For these reasons, cytochrome bd represents a protein target for the development of next-generation antimicrobials.

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KEY WORDS: antimicrobial agents, bacteria, oxidative stress, nitrosative stress, reactive oxygen and nitrogen species, respiratory chain, terminal oxidase, virulence

DOI: 10.1134/S0006297915050077

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