Researchers at the University of Oklahoma’s Center for Antibiotic Discovery and Resistance have made a groundbreaking discovery in the fight against antibiotic resistance. They have identified molecules that inhibit bacterial efflux pumps, thus enhancing the efficacy of antibiotics. This breakthrough offers a promising avenue for new treatments against antibiotic resistance, a concern identified by the World Health Organization.
Antibiotics typically work by targeting specific parts of a bacteria cell, such as the cell wall or DNA. However, bacteria can develop resistance to antibiotics by developing efflux pumps, which are proteins located on the surface of the cell. These efflux pumps effectively pump out antibiotics from the cell before they can kill the bacteria.
Led by Helen Zgurskaya, Ph.D., and Valentin Rybenkov, Ph.D., the Center for Antibiotic Discovery and Resistance at the University of Oklahoma is focused on finding alternative therapeutic solutions. Their recent discovery, published in the journal Nature Communications, showcases the findings of a new class of molecules that inhibit efflux pumps and restore the effectiveness of antibiotics.
The inhibitors identified by the researchers have a novel mechanism of action, which was previously unclear. Collaborating with teams at the Georgia Institute of Technology and King’s College London, Zgurskaya’s team uncovered that these inhibitors work as a “molecular wedge” that targets the area between the inner and outer cell membranes, increasing the antibacterial activities of antibiotics. This understanding of the mechanism behind the inhibitors’ effectiveness opens up possibilities for the discovery of new therapeutics for clinical applications.
Zgurskaya emphasized the urgent need for new solutions to combat antibiotic resistance. She stated, “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.”
The research paper, titled “Conformational restriction shapes the inhibition of a multidrug efflux adaptor protein,” provides more detailed information on the findings. The research team includes 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, and Eamonn Reading.
Helen Zgurskaya is a George Lynn Cross Research Professor, and Valentin Rybenkov is a professor of biochemistry, both in the Department of Chemistry and Biochemistry at the University of Oklahoma’s Dodge Family College of Arts and Sciences. Their research at the Center for Antibiotic Discovery and Resistance holds promise for combating antibiotic resistance and developing new treatments for various infectious diseases.