Modeled structure of AcrAB-TolC multidrug
Multidrug resistance presents a serious problem in the treatment of bacterial infections. This type of bacterial resistance arises due to the overexpression of transporters that recognize and efficiently expel from cells a broad range of structurally unrelated antimicrobial compounds including antibiotics, detergents, dyes and organic solvents. We seek to achieve an understanding of the molecular and biochemical mechanisms of this phenomenon. Specifically, our goal is to elucidate in biochemical terms the mechanism of multidrug transporters of Gram-negative bacteria that cause devastating diseases in animals and human.
We take two converging approaches. One is based on the purification and reconstitution of proteins into the artificial phospholipid bilayer. In this system, we structurally and functionally characterize the individual components of the transport complex, as well as the overall organization of multidrug transporters by using the hydrodynamic, spectroscopic and enzymological techniques. Our second approach is the in vivo and in vitro biochemical evaluation of the individual components, containing genetically engineered mutations in target residues of interest.