Identification of Bacterial Efflux Pump Inhibitors

Bacteria such as Escherichia coli contain efflux pumps (EP) that allow the cell to achieve multi-drug resistance. This phenomenon has been an increasing threat to modern medicine limiting the number of antibiotics available to treat disease. This pump is a tri-partite complex which includes components AcrA, AcrB, and TolC. TolC is a barrel-like protein that spans the bacterial cell’s outer membrane and opens out to the extracellular space. AcrB is a pump that spans the inner membrane and the periplasm. AcrA acts as a bridge that connects TolC to AcrB. Together, they make up the efflux pump which is activated by the proton motive force allowing the cell to expel antibiotics out into the environment, thus keeping the cell from being killed by the antibacterial drugs. To address the multidrug resistance characteristic that these efflux pumps confer on a bacterial cell, we screened a large number of small molecules with the best potential to bind to the tripartite pump and inhibit normal efflux function. After choosing eight of the most promising candidates, we performed efflux assays and tested the ability of the compounds to block efflux of a fluorescent reporter compound, ethidium bromide, from the bacterial cell.https://ecommons.udayton.edu/stander_posters/2035/thumbnail.jp