Synthetic aptamers as potential novel efflux pump inhibitors of the TolC channel in E. coli strains.
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Antibiotic resistance is more than ever one of the most contemporary challenges threatening the health system worldwide. According to World Health Organization, previous cases of bacterial infections - once treatable with antibiotics - can now be lethal due to the uncontrolled misuse of these agents. The emergence of resistance to antibiotics and the dearth of novel drugs currently under development urge the need to search for new effective antibacterials. One of the main triggers of bacterial resistance is the over-expression of multi-drug resistant (MDR) efflux pumps. These pumps allow the bacterium to pump antibiotics out of the cell and therefore desensitizes the cells to the antibacterial inhibitory effect. In this project, we propose to design small chains of nucleic acids called aptamers to bind to and block the outer membrane channel of the efflux pump, which is a protein called TolC, as one effective way to impede antibiotic resistant bacteria from effluxing antibiotics. To generate the DNA aptamers exhibiting a binding specificity to E. coli cells, the method of a whole-cell Systemic Evolution of Ligands by Exponential Enrichement (SELEX) was applied to a random single-stranded DNA library. Whether these aptamers were able to impede the efflux activity of the E. coli pump was then evaluated using an in-vivo efflux assay.
Matthew E. Lopper
Primary Advisor's Department
Stander Symposium project
"Synthetic aptamers as potential novel efflux pump inhibitors of the TolC channel in E. coli strains." (2018). Stander Symposium Projects. 1138.