Carbon Monoxide (CO) and CO-Releasing Molecules (CO-RMs) as Adjuvants to Antibiotics?

Carbon monoxide (CO) – the silent killer – is a respiratory poison of the blood and respiring cells. But surprisingly, CO is produced naturally in biology by haem oxygenase enzymes and has essential roles in cell signalling in higher organisms. Two other toxic gases, nitric oxide (NO) and hydrogen sulfide (H2S) are also produced by bacteria and protect them against antibiotics. Now we have evidence that, unlike NO and H2S, CO gas enhances antibiotic action. This discovery gives impetus to an expanding body of emerging research worldwide that shows that CO generated in living organisms does have antibacterial activity.

Of course, the use of CO in therapy has the considerable disadvantage that, at high concentrations, CO is lethal. Because of the difficulties and dangers of studying CO in the laboratory and using it therapeutically, CO-releasing molecules (CO-RMs) have been devised which release CO only in specific biological environments.  Therapies involving CO or CO-releasing molecules (CO-RMs) have great potential for treating bacterial infections. But our rudimentary knowledge of the modes of actions of CO and CO-RMs limits progress. One intriguing possibility is that because the known targets of CO and CO-RMs in bacteria are different from the targets of antibiotics, CO-RMs or CO gas might be used in combination with conventional antimicrobial agents.

In this research, supported by the Leverhulme Trust, we will:

  • Test the hypothesis that bacterial pathogens may be combatted through application of CO and/or CO-RMs, in combination with other antimicrobial agents like antibiotics
  • Better understand the interactions between CO and antimicrobial agents
  • Obtain new information on the fundamental mechanisms that underlie the antibacterial activity of CO-RMs.

Radically new, interdisciplinary approaches are urgently needed to combat pathogenic microbes, especially antibiotic-resistant 'superbugs' such as MRSA, Clostridium difficile, and common pathogens of the airways and skin. We hope that this work will make a valuable contribution to the exciting new area of gas biology, which straddles, chemistry, microbiology, biochemistry and, potentially, clinical medicine.

Professor Robert Poole
University of Sheffield

Professor Poole was awarded a Leverhulme Trust Research Project Grant in March 2013.