Credit: FDA
Key points:
- Dequalinium chloride (DEQ) curbs mutations in bacteria exposed to ciprofloxacin (cipro)
- Cipro triggers antibiotic resistance by activating a stress-induced mutation mechanism
- DEQ lessened resistance-causing mutations in both cultures and animal models
Researchers have discovered a drug that can reduce antibiotic resistance by slowing bacterial mutation. The drug takes aim at a mutational process induced by one of the most commonly used antibiotics.
A team at Baylor College of Medicine found that dequalinium chloride (DEQ) curbs the development of mutations in E. coli treated with ciprofloxacin (cipro) and two other antibiotics. The study demonstrated for the first time in animal models that cipro, the second-most prescribed antibiotic in the United States, triggers resistance by activating a stress-induced mutation mechanism at low concentrations.
Previous work performed at the same Baylor lab showed that this stress response boosts mutation rates in cipro-treated cell cultures. The process can cause resistance not only to cipro, but to other drugs as well.
In the recent study, the team showed that DEQ counteracts this mutational mechanism in both cultures and infected animals. The paper, published in Science Advances, describes how the researchers screened 1,120 drugs approved for human use for mutation-slowing capabilities targeting the stress response mechanism.
The findings offer a proof-of-concept for evolution-slowing drugs. For this research, the team specifically sought a “stealth” drug that would not block the proliferation of bacteria, and thus would not act as an antibiotic itself.
“We found that DEQ fulfilled both requirements,” said first author Yin Zhai, a postdoctoral associate in Susan Rosenberg’s lab at Baylor College of Medicine. “Given together with cipro, DEQ reduced the development of mutations that confer antibiotic resistance, both in laboratory cultures and in animal models of infection, and bacteria did not develop resistance to DEQ.”
Zhai added that this mutation-slowing effect can be achieved at low DEQ concentrations and that future clinical trials will be needed to determine the drug’s efficacy in patients.