Drug Decelerates Bacterial Race to Antibiotic Resistance
Published:25 Jul.2023 Source:Baylor College of Medicine
A team of researchers at Baylor College of Medicine is gaining ground in their search for solutions to the global problem of bacterial antibiotic resistance, which was responsible for nearly 1.3 million deaths in 2019. The team reports in the journal Science Advances a drug that, in laboratory cultures and animal models, significantly reduces the ability of bacteria to develop antibiotic resistance, which might prolong antibiotic effectiveness. The drug, called dequalinium chloride (DEQ), is a proof-of-concept for evolution-slowing drugs.
In this study, Rosenberg and her colleagues looked for drugs that could prevent or slow down E. coli bacteria from developing resistance to two antibiotics when exposed to a third antibiotic, ciprofloxacin (cipro), the second most prescribed antibiotic in the U.S. and one associated with high bacterial resistance rates.The resistance is caused by new gene mutations that occur in the bacteria during infection. Previous work from the Rosenberg lab had shown that bacterial cultures in the lab exposed to cipro turn up mutation rate. They found a mutational "program" that is switched on by bacterial stress responses. The same stress responses also increase the ability to make genetic mutations, the Rosenberg group, then many other labs, have shown.Bacteria with antibiotic resistance mutations can then sustain an infection in the presence of cipro. This study is the first to show that in animal infections treated with cipro, the bacteria activate a known stress-induced genetic mutational process.
Looking to prevent the development of antibiotic resistance, the researchers screened 1 120 drugs approved for human use for their ability to dial down the master bacterial stress response, which they showed counters the emergence of resistance mutations.