Postdoctoral researcher Arnau Domenech and his colleagues identified a new pathway for disrupting the ability of bacteria cells to develop antibiotic resistance. Photo by Veening Lab
March 3 (UPI) -- According to a new study, scientists have developed a drug that prevents bacteria from acquiring the genes needed to develop antibiotic resistance.
Bacteria evolve resistance to antibiotics by acquiring DNA fragments from their environs and incorporating them into their genomes. This ability is referred to as "competence."
Through a series of observations and lab tests, scientists were able to identify the chain of events that allow bacteria cells to become competent. Once they identified what competence looked like, scientists were able to identify drugs that interfered with the process.
"We collaborated with scientists from Heidelberg, who developed a high-throughput assay to simultaneously test cells for competence and growth," lead study author Arnau Domenech, postdoctoral researcher at the University of Groningen in the Netherlands, said in a news release. "In this assay, 1,366 approved drugs were screened. It turned out that 46 of them blocked the induction of competence, without negatively affecting growth."
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Cells can become motivated to evolve defenses against drugs if the drugs cause growth stress. Because the 46 drugs don't negatively impact cell growth, cells of the bacterium Streptococcus pneumoniae didn't develop resistance.
The drugs that prevented competence and didn't inhibit cell growth belonged to two different categories: drugs affecting ion homeostasis and antipsychotics. Further investigation showed that all of the drugs block competence by disrupting the proton-motive force, the electrochemical gradient that propels protons cellular membranes and fuels a variety of cellular processes.
"The result is that the cells fail to secrete a peptide called CSP," said Domenech.
When enough cells secrete CSP, competence genes get activated -- a process known as quorum sensing. By disrupting the proton-motive force, the 46 drugs prevented CSP secretion from crossing the necessary threshold and turning on the competence genes.
"In the lab, we observed that our competence-blocking drugs could prevent the transfer of antibiotic resistance genes to susceptible strains of Streptococcus pneumoniae and we obtained the same results in cultures of human lung epithelial cells," Domenech said.
Scientists got the same promising results when they repeated the lab tests using a mouse model. The research team published the results of their tests this week in the journal Cell Host and Microbe.
Cells can become motivated to evolve defenses against drugs if the drugs cause growth stress. Because the 46 drugs don't negatively impact cell growth, cells of the bacterium Streptococcus pneumoniae didn't develop resistance.
The drugs that prevented competence and didn't inhibit cell growth belonged to two different categories: drugs affecting ion homeostasis and antipsychotics. Further investigation showed that all of the drugs block competence by disrupting the proton-motive force, the electrochemical gradient that propels protons cellular membranes and fuels a variety of cellular processes.
"The result is that the cells fail to secrete a peptide called CSP," said Domenech.
When enough cells secrete CSP, competence genes get activated -- a process known as quorum sensing. By disrupting the proton-motive force, the 46 drugs prevented CSP secretion from crossing the necessary threshold and turning on the competence genes.
"In the lab, we observed that our competence-blocking drugs could prevent the transfer of antibiotic resistance genes to susceptible strains of Streptococcus pneumoniae and we obtained the same results in cultures of human lung epithelial cells," Domenech said.
Scientists got the same promising results when they repeated the lab tests using a mouse model. The research team published the results of their tests this week in the journal Cell Host and Microbe.
RELATED Bacterial evolution of antibiotic weapons promises new insights for drug makers
Because the proton-motive force is necessary for some vital functions in humans, scientists aren't certain whether drugs are safe for humans. Further testing is needed to determine whether these anti-evolution drugs can help
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