Silas Miller, a student in the Cellular and Molecular Biology Graduate Program and a member of the Raman Lab, has been awarded a F31 grant from the National Institutes of Health. The prestigious grant will support Miller’s research and stipend as he explores mechanisms responsible for antibiotic resistance in infectious bacteria.
“Transport proteins are clinically relevant because they contribute to drug resistance in bacteria. But, we don’t really know how efflux pumps, a type of transport protein, recognize antibiotics,” says Miller. “Creating drugs that will inhibit transport proteins could restore efficacy of antibiotics or help prevent or slow down antibiotic resistance in the first place.”
While many transport proteins bind to and transport specific molecules, multidrug efflux pumps recognize and bind to a wide array of molecules, allowing bacterial cells to purge multiple types of antibiotics. Targeting multidrug efflux pumps may be a way to treat antibiotic-resistant bacterial infections.
Miller’s research seeks to learn more by studying a multidrug efflux pump found in Staphylococcus aureus, a bacterium that infects more than 100,000 people annually according to the Centers for Disease Control and Prevention, and that can be notoriously difficult to treat with antibiotics.
Miller is screening every possible variation of the efflux pump created by a mutation made to a single amino acid. His data will determine which mutations inhibit the pump’s ability to transport antibiotics, making the bacteria more susceptible to antibiotic treatment. He will then further analyze the mutations that increase antibiotic susceptibility to determine whether the mutation impacts how the pump binds to an antibiotic or the amount of energy available to transport the antibiotic.
“I’m really grateful for this grant and the support for this research,” says Miller. “In the Raman Lab, I’ve had a lot of freedom to find what interests me and build this project. With the grant, I can continue to work closely with my advisor and lab mates, and I’m also able to collaborate with scientists in the Henzler-Wildman Lab. Their expertise in the energetics of efflux pumps is essential to this research, and we can make more progress thanks to this collaboration.”
Written by Renata Solan.