Gasotransmitters, poisons, and antimicrobials: it's a gas, gas, gas!

Abstract

We review recent examples of the burgeoning literature on three gases that have major impacts in biology and microbiology. NO, CO and H2S are now co-classified as endogenous gasotransmitters with profound effects on mammalian physiology and, potentially, major implications in therapeutic applications. All are well known to be toxic yet, at tiny concentrations in human and cell biology, play key signalling and regulatory functions. All may also be endogenously generated in microbes. NO and H2S share the property of being biochemically detoxified, yet are beneficial in resisting the bactericidal properties of antibiotics. The mechanism underlying this protection is currently under debate. CO, in contrast, is not readily removed; mounting evidence shows that CO, and especially organic donor compounds that release the gas in biological environments, are themselves effective, novel antimicrobial agents.

Nitric Oxide: Exploring the Contextual Link with Alzheimer’s Disease

“…Although research to work out the molecular mechanisms underlying the cause and the progression of the disease is advancing rapidly, we are yet to do as much with respect to therapeutics. Currently, there is no absolute cure for AD: the few drugs available to clinicians [9] do alleviate the clinical symptoms. Therefore, it is more pertinent than ever that we devise therapeutic strategies that can arrest the disease in total absoluteness.…”

“…For many years, NO had been known pretty much for its noxious effects to the body [9]. As a result, its potential beneficial roles were of petite significance to the scientific sphere.…”

Carbon Monoxide-releasing Molecule-3 (CORM-3; Ru(CO)3Cl(Glycinate)) as a Tool to Study the Concerted Effects of Carbon Monoxide and Nitric Oxide on Bacterial Flavohemoglobin Hmp

“…One of the most attractive features of CO-RMs is the fact that they appear to be more effective than CO gas. Indeed, bacterial growing cells are inhibited by CORM-3 but not by the same concentration of dissolved CO gas, suggesting that the CO-RM is taken up by the cells delivering the CO in situ (50,64,65); this has been called "The Trojan horse mechanism" (64,66). However, data concerning the modes of action of CO and CO-RMs in biological systems are still very limited.…”

Hydrogen Sulfide (H2S) is a Mediator of Nitric Oxide (NO) Signaling Functions in Bacteria

“…They are toxic at high doses, but at the physiological doses they play the outstanding regulatory and signaling role. In 2006 H 2 S has been denominated on a "clandestine microbial messenger" [7].…”

“…H 2 S potentates the signaling effects of NO, so that both these gases can act synergistically. In E. coli mutants deficient in H 2 S production the higher amounts of NO have been synthesized [7].…”