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Vortrag von Martin Pos

Vortragstitel: "From mechanism to inhibition: Bacterial efflux pumps in antimicrobial resistance"
Anlass: SFB-Seminar
Beginn: 11.12.2025, 14:15 Uhr
Ort: CellNanOs, 38/201

Über den Vortragenden: Prof. Dr. Martin Pos forscht am Institut für Biochemise an der Goethe Universität in Frankfurt

Bacteria can resist antibiotics by actively pumping toxic compounds out of the cells. In Gram-negative bacteria, multi-component drug efflux systems span the bacterial cell envelope and consist of three parts: an inner membrane transporter that selects drugs and converts energy to drive export, a periplasmic adaptor that connects the components and forms a conduit through the periplasm, and an outer membrane channel through which the drugs are released. In Escherichia coli, the transporter AcrB of the AcrAB-TolC pump can recognize and expel a remarkably broad range of substances, including antibiotics, bile salts, detergents, and dyes. The process is energized by the proton motive force, and the drug export is coupled to the transfer of protons from the periplasm to the cytoplasm through the AcrB transmembrane domain. The system is highly allosteric as AcrB is a trimer where each protomer adopts three conformational states in a sequential and interdependent cyclic fashion with high analogy to the binding change mechanism catalyzing ATP synthesis by the F₁F_o-ATP-synthase.

By combining structural and biochemical approaches, we were able to explore how AcrB accommodates such diverse molecules and guides them along different pathways through the pump. The uptake and binding of protons trigger conformational changes and support the directionality of drug efflux. We further identified how two distinct classes of small-molecule inhibitors block AcrB and bind to separate sites, thereby shutting down this resistance mechanism.