Matthew Lopper, Ph.D.
The increasing prevalence of multidrug-resistant bacteria has become a major concern for public health, due in part to the high cost of treatment. One factor contributing to this resistance is the overexpression of bacterial efflux pumps, proteins located on the cell membrane that can pump out antibiotics as they enter the cell. To address this issue, this research aims to develop a DNA-based inhibitor, called an aptamer, to target the TolC component of the bacterial efflux pump and inhibit its function. By blocking the TolC, it is expected that this will reverse the multidrug resistance phenotype and make bacteria sensitive to antibiotics that were previously ineffective. The aptamers will be generated from a single stranded DNA library using a systematic evolution of ligands by exponential enrichment (SELEX) process, which involves selecting and amplifying DNA molecules that bind to TolC. The optimization of asymmetric and symmetric PCR techniques is done to ensure that single stranded DNA was amplified efficiently. SELEX rounds have not been completed with oML407, however, with the parameters established the next steps will be to run several rounds of this process. Once the TolC-binding aptamers have been identified, they can be synthesized and evaluated for their efficacy as agents to sensitize bacteria to antibiotics. The successful development of aptamers as inhibitors of the TolC component of the bacterial efflux pump has the potential to have a major impact on public health.
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MItzka, Lara M., "Synthesis of a Single Stranded DNA Aptamer to Inhibit Multidrug Resistance Caused by Bacterial Efflux Pump Overexpression" (2023). Honors Theses. 409.
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