Synthesis Of a Single Stranded DNA Aptamer to Inhibit Multidrug Resistance Caused by Bacterial Efflux Pump Overexpression

Synthesis Of a Single Stranded DNA Aptamer to Inhibit Multidrug Resistance Caused by Bacterial Efflux Pump Overexpression

Presenter(s)

Lara Mitzka

Comments

Presentation: 2:40-3:00 p.m., Kennedy Union 222

Description

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 which are proteins located in 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 selected 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 to ensure that single stranded DNA is amplified efficiently as well as several SELEX rounds was successfully completed. Currently, SELEX rounds are being analyzed to determine if any active aptamers were recovered. Once the TolC-binding aptamers have been identified, they will 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.

Publication Date

4-19-2023

Project Designation

Honors Thesis

Primary Advisor

Matthew Lopper

Primary Advisor's Department

Chemistry

Keywords

Stander Symposium, College of Arts and Sciences

Synthesis Of a Single Stranded DNA Aptamer to Inhibit Multidrug Resistance Caused by Bacterial Efflux Pump Overexpression

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