Researchers at the University of Oklahoma's Center for Antibiotic Discovery and Resistance have discovered molecules that inhibit bacterial efflux pumps, thereby enhancing the effectiveness of antibiotics. The breakthrough involves a "molecular wedge" mechanism and offers a promising avenue for new treatments to combat antibiotic resistance.
The World Health Organization has identified antimicrobial resistance as a global concern because most clinical antibiotics are no longer effective against certain pathogenic bacteria. The University of Oklahoma's Center for Antibiotic Discovery and Resistance, led by Helen Zgurskaya, Ph.D., and Valentin Rybenkov, Ph.D., is working to find alternative treatment solutions.
Antibiotics work by targeting specific parts of the bacterial 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 located on the surface of bacterial cells). When an antibiotic enters a cell, an efflux pump pumps it out of the cell before it reaches its target, so the antibiotic never kills the bacteria.
However, researchers at the University of Oregon recently published a finding in the journal Nature Communications. Scientists have discovered a new class of molecules that inhibit efflux pumps, allowing antibiotics to work again.
These inhibitors have novel mechanisms of action that until recently remained unclear. Zgurskaya's team, working with teams at Georgia Institute of Technology and King's College London, UK, discovered that these inhibitors act as "molecular wedges" that target the region between the inner and outer membranes of cells, enhancing the bacteria's antimicrobial activity. Understanding this mechanism could facilitate the discovery of new therapies for clinical application of antibiotics.
"We are already living in a post-antibiotic era, and unless new solutions to antibiotic resistance are found in clinics, the situation will get worse. Our findings will facilitate the development of new treatments to help alleviate the looming crisis," said Zgurskaya.