Martin-Luther-Universität Halle-Wittenberg

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Ghada Abou Ammar, M. Sc.

Inhibitors of efflux transporters

 Resistance to drugs is a growing problem in several systems, including pathogenic microorganisms such as bacteria and fungi or in human tumor cells. In most cases investigated so far, drug resistance is adaptive and mediated by efflux transporters, which are overexpressed in cells stressed by toxic compounds such as antibiotics, fungicides or cytostatics. ABC (ATP-Binding Cassette) is a class of efflux transporters which use the energy of ATP hydrolysis to transfer toxic compounds across membranes, and are exhibit rather broad substrate specificity and are able to extrude a large number of structurally highly diverse compounds. Thus, individual or several transporters in a concerted action are able to maintain the intracellular concentration of toxic compounds below a critical threshold and allow growth of cells expressing efflux transporter genes even in the presence of antibiotics, fungicides or cytostatics.

Objectives

 The goal of this project is to:

  • clone different fungal efflux transporter genes and to express them in transporters-deficient yeast cells
  • investigate the substrate specificity and the role(s) of individual efflux transporters of fungi pathogenic on humans and on plants, this will add to understanding of the phenomenon of multidrug resistance and the tools generated, i.e. transgenic yeast strains, may allow estimating efficacies and resistance risk of novel drugs.
  • identify plant-derived inhibitors of efflux transporters. This may allow large-scale production in fermentors of efficient inhibitors for medicinal or agricultural purposes.

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