Research led by Baylor College of Medicine shows slowing bacterial evolution using dequalinium chloride could be an alternative route to combating the ongoing problem of antibiotic resistance.
“Most people with bacterial infections get better after completing antibiotic treatment, but there are also many cases in which people decline because the bacteria develop resistance to the antibiotic, which then can no longer kill the bacteria,” said lead investigator Susan Rosenberg, Ben F. Love Chair in Cancer Research and professor of molecular and human genetics at Baylor, in a press statement.
Dequalinium chloride was first discovered in 1956 and has been used as an antiseptic and disinfectant compound, for example, in lozenges, mouthwashes and creams for many years.
In this study, which is published in Science Advances, Rosenberg and colleagues showed dequalinium chloride can also slow down the ability of Escherichia coli bacteria to evolve and become resistant to antibiotic drugs.
They started by looking for a drug compound that could stop E. coli developing resistance to ciprofloxacin, the second most commonly prescribed antibiotic in the U.S. that triggers high resistance rates. They screened 1120 previously approved drugs to search for a candidate that had the potential to slow bacterial evolution.
Rosenberg and team found that dequalinium chloride reduced the speed that E. coli produced new mutations, which are the reason resistance develops. Under normal circumstances, exposure to ciprofloxacin triggers a stress response in E. coli that in turn triggers bacterial mutagenesis as a survival response. Dequalinium chloride was able to block this stress response in the bacteria without in turn triggering resistance to its own effects.
“Given together with ciprofloxacin, dequalinium chloride 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 dequalinium chloride,” said first author Yin Zhai, a postdoctoral associate in the Rosenberg lab. “In addition, we achieved this mutation-slowing effect at low dequalinium chloride concentrations, which is promising for patients.”
To ensure its safety and effectiveness, the researchers emphasize that dequalinium chloride will need to be tested in clinical trials in the future to further validate these results.
The authors also note that if proved effective, dequalinium chloride could even be used to treat infections without use of an additional antibiotic. “Slowing pathogen evolution might allow immune response somatic evolution to outstrip the pathogen to allow clearance of infections without harm to the native human microbiome,” they write.
