Development of synthetic DNAs to inhibit the TolC protein in the fight against antibiotic resistance
Bacterial resistance to antibiotics has become a major threat to our public health system. Multidrug resistant bacterial infections are often acquired in a clinical setting and treatment options are often limited. Due to the ability of bacteria to reproduce very quickly and adapt to a wide variety of environments, bacterial cell evolution seems to be outpacing our ability to discover new antibiotics. While there are many ways for bacterial cells to resist the killing effects of our antibiotics, one mechanism that can lead to a multidrug resistance characteristic is the overexpression of efflux pump proteins. These integral proteins in the bacterial cell membrane, composed of AcrA, AcrB, and TolC, can export antibiotics before they can exert their killing effects on the bacterial cell. The goal of this research is to address this issue by targeting the efflux pumps with novel single-stranded DNA-based inhibitors. Similar to a cork in a bottle, single-stranded DNA molecules that can bind to the TolC component of the efflux pump could block efflux, thus resensitizing the bacterial cell to antibiotics. Here, we use a process called SELEX to select for specific sequences of single-stranded DNA from a randomized single-stranded DNA library that have a high affinity for binding to E. coli TolC. This approach could be applied to clinically-important multidrug resistant bacterial strains, which we hope will improve many antibacterial treatment options.
Primary Advisor's Department
Stander Symposium, College of Arts and Sciences
Institutional Learning Goals
"Development of synthetic DNAs to inhibit the TolC protein in the fight against antibiotic resistance" (2023). Stander Symposium Projects. 3142.