While many bacteria are developing a resistance to antibiotics, a gas harmful to humans in large doses could actually be our secret weapon.
It seems hard to avoid all the talk of an ‘antibiotic apocalypse’ these days, especially when an influential body such as the World Health Organisation has issued a desperate plea on more than one occasion for pharmaceutical researchers to find new drug candidates.
In the meantime, however, a team of researchers from Georgia State University in the US has found a way to significantly boost the power of existing antibiotics in what would appear an unlikely source: carbon monoxide.
The noxious gas is particularly harmful to humans in large doses, with a carbon monoxide alarm a common item in many people’s homes.
In the pharmaceutical business, however, it has an altogether more positive effect by a factor of 25.
In a paper published to Organic Letters, the research team found that when it paired carbon monoxide with the antibiotic metronidazole, the gas enhanced the efficacy of the antibiotic against H pylori, a type of bacteria that infects the stomach and causes peptic ulcers.
Because the gas is produced naturally in the human body, it is essential for our survival and plays an important role in reducing inflammation, promoting cell proliferation and regulating cellular immune response to pathogens.
Resensitising the bacteria
For the study, the team developed a prodrug system that releases three components: carbon monoxide, metronidazole and a fluorescent molecule used to monitor the release of carbon monoxide.
A prodrug is the state before a drug becomes effective, as it must undergo a chemical conversion before becoming an active pharmacological agent, but can be triggered once it is placed in water.
“We always hear about the discussions of drug resistance. When we have drug resistance, it’s not because these bacteria will not respond to antibiotics anymore,” said Dr Binghe Wang of the research team.
“Most of the time, it means there is decreased sensitivity. If you can resensitise bacteria or sensitise them, then that would allow you to either use a smaller amount of antibiotic or use the same amount that would kill many, many more bacteria.”
Updated, 4.46pm, 22 February 2018: The article has been amended to correct previous statements concerning the effects of carbon monoxide.