Carbon Monoxide-Releasing Compounds as Novel Antibacterial Drugs

A team of British molecular microbiologists has demonstrated the potential use of carbon monoxide (CO)-releasing compounds for treatment of gonorrhea.

Gonorrhea, which is caused by the bacterium Neisseria gonorrhoeae, has developed some highly drug-resistant strains, which has raised concern that the second most common sexually transmitted infection in England may become untreatable.

Investigators at the University of York have been examining the potential for carbon monoxide-releasing molecules (CO-RMs) as antimicrobial agents, which represents an exciting prospective in the fight against antibiotic resistance. This field is especially attractive since Trypto-CORM, a tryptophan-containing manganese(I) carbonyl compound, was shown to be toxic against E. coli following photo-activation.

The investigators reported in the December 6, 2016, online edition of the journal MedChemComm that Trypto-CORM was toxic against Neisseria gonorrhoeae in the absence of photoactivation. Trypto-CORM toxicity could be reversed by the high CO affinity globin leg-hemoglobin (Leg-Hb), indicating that the toxicity was due to CO release.

Release of CO from Trypto-CORM in the dark was also detected with Leg-Hb (but not myoglobin) in vitro. Since N. gonorrhoeae is more sensitive to CO-based toxicity than other model bacterial pathogens, it may prove to be a viable candidate for antimicrobial therapy using CO-RMs.

Contributing author Dr. Ian Fairlamb, professor of chemistry at the University of York, said, "The carbon monoxide molecule targets the engine room, stopping the bacteria from respiring. Gonorrhea only has one enzyme that needs inhibiting and then it cannot respire oxygen and it dies. People will be well aware that CO is a toxic molecule but that is at high concentrations. Here we are using very low concentrations, which we know the bacteria are sensitive to. We are looking at a molecule that can be released in a safe and controlled way to where it is needed. We think our study is an important breakthrough. It is not the final drug yet but it is pretty close to it. People might perceive gonorrhea as a trivial bacterial infection, but the disease is becoming more dangerous and resistant to antibiotics."