A team of researchers at the University of York, UK, has harnessed the therapeutic effects of carbon monoxide-releasing molecules to develop a new antibiotic which could be used to treat gonorrhea, a sexually transmitted disease caused by Neisseria gonorrhoeae bacteria.
This illustration depicts a 3D computer-generated image of a number of drug-resistant Neisseria gonorrhoeae diplococcal bacteria. Note that extending from the organisms’ exterior were type IV pili, or hair-like appendages, which in this case, are used to promote motility for these bacteria, and improve surface adherence. The artistic recreation was based upon scanning electron microscopic imagery. Image credit: U.S. Centers for Disease Control and Prevention.
In recent years Neisseria gonorrhoeae has developed resistance to almost every class of antibiotics used for gonorrhea treatment: sulfonilamides, penicillin, tetracycline, and fluoroquinolones, such as ciprofloxacin. There are concerns that the disease is becoming untreatable.
Professor James Moir, from the University of York’s Department of Biology, and his colleagues targeted the ‘engine room’ of Neisseria gonorrhoeae using carbon monoxide-releasing molecules (CO-RMs).
CO is produced naturally in the body, but there is increasing evidence that carbon monoxide enhances antibiotic action with huge potential for treating bacterial infections.
Prof. Moir and co-authors found that Neisseria gonorrhoeae is more sensitive to CO-based toxicity than other model bacterial pathogens, and may serve as a viable candidate for antimicrobial therapy using CO-RMs.
The CO molecule works by binding to the bacteria, preventing them from producing energy.
The team believes the breakthrough could pave the way for new treatments.
“The CO molecule targets the engine room, stopping the bacteria from respiring,” said co-author Prof. Ian Fairlamb, from the University of York’s Department of Chemistry.
“Gonorrhea only has one enzyme that needs inhibiting and then it can’t 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.”
According to the researchers, the next stage is to develop a drug, either in the form of a pill or cream, so that the fundamental research findings can be translated on to future clinical trials.
“We think our study is an important breakthrough. It isn’t the final drug yet but it is pretty close to it,” Prof. Fairlamb said.
“People might perceive gonorrhea as a trivial bacterial infection, but the disease is becoming more dangerous and resistant to antibiotics.”
“Antimicrobial resistance is a massive global problem which isn’t going away,” Prof. Moir said.
“We need to use many different approaches, and the development of new drugs using bioinorganic chemistry is one crucial way we can tackle this problem, to control important bacterial pathogens before the current therapies stop working.”
The findings were published online Dec. 6, 2016 in MedChemComm, the official journal of the European Federation for Medicinal Chemistry.
_____
Jonathan S. Ward et al. Toxicity of tryptophan manganese(I) carbonyl (Trypto-CORM), against Neisseria gonorrhoeae. MedChemComm, published online December 6, 2016; doi: 10.1039/c6md00603e
