Antibiotics work by targeting specific parts of a bacteria cell, such as the cell wall or its DNA. Bacteria can become resistant to antibiotics in a number of ways, including by developing efflux pumps — proteins that are located on the surface of the bacteria cell. When an antibiotic enters the cell, the efflux pump pumps it out of the cell before it can reach its target so that the antibiotic is never able to kill the bacteria.
The World Health Organization has labeled antimicrobial resistance a global threat because most clinical antibiotics are no longer effective against certain pathogenic bacteria.
However, OU researchers have contributed with a new discovery in which they found a new class of molecules that inhibit the efflux pump and make the antibiotic effective again.
The inhibitors have a novel mechanism of action, which until recently remained unclear. Zgurskaya’s team have uncovered that these inhibitors work as a “molecular wedge” that targets the area between the inner and outer cell membranes and increases antibacterial activities of antibiotics. Understanding this mechanism can facilitate the discovery of new therapeutics for clinical applications.
“We already live in a post-antibiotic era, and things will get much worse unless new solutions are found for antibiotic resistance in clinics. The discoveries we’ve made will facilitate the development of new treatments to help mitigate an impending crisis,” Zgurskaya said.
Benjamin Russell Lewis, Muhammad R. Uddin, Mohammad Moniruzzaman, Katie M. Kuo, Anna J. Higgins, Laila M. N. Shah, Frank Sobott, Jerry M. Parks, Dietmar Hammerschmid, James C. Gumbart, Helen I. Zgurskaya, Eamonn Reading. Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein. Nature Communications, 2023; 14 (1) DOI: 10.1038/s41467-023-39615-x
University of Oklahoma. “Researchers discover method to overcome antimicrobial resistance.” ScienceDaily. ScienceDaily, 31 July 2023. <www.sciencedaily.com/releases/2023/07/230731151545.htm>.
Photo by Nastya Dulhiier