Drugs help reduce antibiotic resistance in bacteria

A team of researchers at Baylor College of Medicine in the United States is making progress in their search for solutions to global problems. bacterial antibiotic resistanceabout 1.3 million people died in 2019.

Team reports in journals scientific progress When cultured in the laboratory, animal modelsignificantly reduce the ability of bacteria It can develop antibiotic resistance and prolong the effects of antibiotics. The drug called dequalinium chloride (DEQ) is a proof-of-concept drug that slows evolution.

“Most patients with bacterial infections improve their symptoms after completing antibiotic treatment, but many cases become debilitating because the bacteria develop resistance to antibiotics and are unable to kill them.” Corresponding author Susan M. Rosenberg, Ph.D. He is Professor of Molecular and Genetics, Biochemistry and Molecular Biology, Molecular Virology and Microbiology at Baylor University.

In this study, Rosenberg and her colleagues looked for drugs that could prevent or slow progression. Escherichia coli Prevents bacteria from developing resistance to two antibiotics when exposed to a third antibiotic. Ciprofloxacin (Cipro), the second most prescribed antibiotic in the United States and an antibiotic associated with high rates of bacterial resistance.

Resistance is caused by new genetic mutations that develop within the bacterium during infection.medicine DEQ The research team found that it slows down the rate at which new mutations form in bacteria.

past works Researchers in the Rosenberg lab showed that bacterial cultures in the lab were exposed to: Cipro Increase mutation rate. They discovered a mutational ‘program’ that is switched on by the bacterial stress response. The stress response is a genetic program that instructs cells to increase the production of protective molecules during stress, such as stress from low levels of stress. Cipro. Low levels occur at the beginning and end of antibiotic therapy and when doses are forgotten.

Rosenberg’s group, and many other laboratories, have shown that the same stress response increases the ability to mutate genes. Some mutations also confer resistance. CiproOn the other hand, other mutations may enable resistance to yet-to-be-encountered antibiotics. The mutagenesis process activated by the stress response is called the stress-induced mutational mechanism.

Bacteria with antibiotic resistance mutations become able to maintain infection even in the presence of antibiotics. Cipro. This study has shown that in the treatment of animal infections, Ciprobacteria activate known stress-induced gene mutation processes. Cipro Resistance arises primarily through the expression of new mutations in bacteria, both clinically and in the laboratory, rather than by acquiring genes conferring antibiotic resistance from other bacteria.

Aiming to prevent the emergence of antibiotic resistance, researchers screened 1,120 drugs approved for human use for their ability to quell key bacterial stress responses, which could lead to the emergence of resistance mutations. indicated to stop. In addition, counterintuitively, they wanted a “stealth” drug that would not slow the growth of bacteria. This provides a growth advantage for bacterial mutants that are resistant to the mutation-suppressing drug itself. In other words, it is a drug that is not an antibiotic.

“We discovered that DEQ I met both requirements. It is given together with Cipro, DEQ In both laboratory cultures and animal models of infection, the occurrence of antibiotic resistance-conferring mutations was reduced, and bacteria did not develop resistance to antibiotics. DEQconcluded lead author Ying Zai, a postdoctoral fellow in the Rosenberg lab. “Furthermore, we achieved this mutation-suppressing effect at low temperatures. DEQ This is a promising concentration for patients. Future clinical trials are needed to assess the ability of DEQ To slow down bacterial antibiotic resistance in patients. “