Carbon monoxide in biology and microbiology: surprising roles for the "Detroit perfume".

Carbon monoxide (CO) is a colorless, odorless gas with a reputation for being an anthropogenic poison; there is extensive documentation of the modes of human exposure, toxicokinetics, and health effects. However, CO is also generated endogenously by heme oxygenases (HOs) in mammals and microbes, and its extraordinary biological activities are now recognized and increasingly utilized in medicine and physiology. This review introduces recent advances in CO biology and chemistry and illustrates the exciting possibilities that exist for a deeper understanding of its biological consequences. However, the microbiological literature is scant and is currently restricted to: 1) CO-metabolizing bacteria, CO oxidation by CO dehydrogenase (CODH) and the CO-sensing mechanisms that enable CO oxidation; 2) the use of CO as a heme ligand in microbial biochemistry; and 3) very limited information on how microbes respond to CO toxicity. We demonstrate how our horizons in CO biology have been extended by intense research activity in recent years in mammalian and human physiology and biochemistry. CO is one of several "new" small gas molecules that are increasingly recognized for their profound and often beneficial biological activities, the others being nitric oxide (NO) and hydrogen sulfide (H2S). The chemistry of CO and other heme ligands (oxygen, NO, H2S and cyanide) and the implications for biological interactions are briefly presented. An important advance in recent years has been the development of CO-releasing molecules (CO-RMs) for aiding experimental administration of CO as an alternative to the use of CO gas. The chemical principles of CO-RM design and mechanisms of CO release from CO-RMs (dissociation, association, reduction and oxidation, photolysis, and acidification) are reviewed and we present a survey of the most commonly used CO-RMs. Amongst the most important new applications of CO in mammalian physiology and medicine are its vasoactive properties and the therapeutic potentials of CO-RMs in vascular disease, anti-inflammatory effects, CO-mediated cell signaling in apoptosis, applications in organ preservation, and the effects of CO on mitochondrial function. The very limited literature on microbial growth responses to CO and CO-RMs in vitro, and the transcriptomic and physiological consequences of microbial exposure to CO and CO-RMs are reviewed. There is current interest in CO and CO-RMs as antimicrobial agents, particularly in the control of bacterial infections. Future prospects are suggested and unanswered questions posed.