Introduction:
Researchers at Baylor College of Medicine are making progress in their quest to address the global issue of bacterial antibiotic resistance, which resulted in nearly 1.3 million deaths in 2019. In a study published in the journal Science Advances, the team presents a drug called dequalinium chloride (DEQ) that demonstrates the ability to significantly reduce bacteria's development of antibiotic resistance in laboratory cultures and animal models. This breakthrough drug holds promise as a potential solution to prolong the effectiveness of antibiotics and combat resistance.
Study Findings:
The researchers focused on finding drugs that could hinder or slow down the development of antibiotic resistance in Escherichia coli (E. coli) bacteria when exposed to ciprofloxacin (cipro), the second most prescribed antibiotic in the United States known for its high bacterial resistance rates. The resistance is caused by new gene mutations that occur in the bacteria during infection.
The drug DEQ was found to slow down the formation of new mutations in bacteria, effectively reducing the speed at which they develop antibiotic resistance. Previous research by the team had identified a stress-induced mutation mechanism that increases the mutational rate in bacteria under stress, including exposure to low concentrations of cipro. This study demonstrated that animal infections treated with cipro also activate this stress-induced genetic mutational process.
To identify drugs that counteracted the emergence of resistance mutations, the researchers screened 1,120 drugs approved for human use. They sought drugs that suppressed the master bacterial stress response while not impeding bacterial proliferation, as slowing bacterial growth could confer an advantage to mutants resistant to the mutation-slowing drug itself.
DEQ fulfilled both criteria, effectively reducing the development of mutations that confer antibiotic resistance in laboratory cultures and animal models of infection when administered together with cipro. Importantly, bacteria did not develop resistance to DEQ itself. The mutation-slowing effect was observed at low DEQ concentrations, making it a promising candidate for future clinical trials aimed at decelerating bacterial antibiotic resistance in patients.
Conclusion:
The discovery of DEQ as a drug that slows the development of antibiotic resistance in bacteria provides hope in the battle against this global health challenge. By targeting the stress-induced mutation mechanisms, DEQ demonstrates potential for extending the effectiveness of antibiotics and reducing the emergence of resistant bacterial strains. Further research and clinical trials are required to fully evaluate the efficacy of DEQ in combating antibiotic resistance in patients. The study's findings contribute to the ongoing efforts to address antibiotic resistance, a critical issue in modern medicine.
