In this edition:
Research from the Raman and Henzler-Wildman Labs in the Department of Biochemistry uncovers new details about how bacterial cells balance energetic needs to expel antibiotics. Here’s the run down on their latest research, published in PNAS:
What background information do you need to know?
Cells use energy to expel unwanted molecules through various transport proteins. One important class of these proteins is efflux pumps, which sit in the cell membrane and remove harmful substances, such as metals, toxins, and metabolic waste, from the cell. While most transport proteins interact with only a few specific molecules, many efflux pumps can recognize and remove a wide range of molecules, an ability known as broad specificity. The relationship between an efflux pump’s energy requirements and the breadth its specificity is not known.
Why does this matter?
Efflux pumps play critical roles in human health and disease. In bacterial and cancer cells, mutations can enable these pumps to recognize and expel a broad range of antibiotics or chemotherapeutic agents, driving multidrug resistance. Targeting these pumps offers a potential strategy for treating resistant infections and tumors.
Efflux pumps also have implications for bioenergy research. The industrial processes used when microbes produce biofuels can result in toxic byproducts that inhibit microbe growth, impacting their biofuels production. Engineering efflux pumps that selectively remove these toxic compounds has potential to enhance biofuel production.
How have scientists made progress?
Led by graduate student Silas Miller, the Raman and Henzler-Wildman Labs screened all possible single-point mutations of a multidrug efflux pump from Staphylococcus aureus, a notoriously difficult-to-treat bacterium that infects more than 100,000 people in the U.S. each year (Centers for Disease Control and Prevention). The researchers then analyzed how each mutation affected the pump’s broad specificity and energy efficiency.
Their results suggest a link between broad specificity and energy efficiency: mutated pumps that demonstrated broad specificity were also more energetically efficient. These findings indicate that mutations altering specificity, energy use, or both could inform biofuel production and serve as potential targets for combating drug-resistant pathogens.
Written by Renata Solan.
In Research In Brief: The What, Why, and How, we explore new research from the UW–Madison Department of Biochemistry to learn more about the world around us — and inside us.
This edition of Research in Brief: The What, Why, and How is based on the following publication: Miller, Henzler-Wildman, and Raman. Energetic and structural control of polyspecificity in a multidrug transporter. PNAS, 2025, 122(52):e2511892122. This research was funded in part by the National Institutes of Health (NIH) and the U.S. Department of Energy.