ZGURSKAYA, HELEN - University of Oklahoma - Department of Chemistry and Biochemistry

个人简介

BS, 1989, Dnepropetrovsk State University, Ukraine PhD, 1992, Russian Academy of Sciences, Russia Postdoc, 1995-1996, Stanford University School of Medicine; 1996-1999, University of California, Berkeley

研究领域

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.

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Tikhonova, E.B., Devroy, V., Rybenkov, and Zgurskaya, H.I. Kinetic control of TolC recruitment by multidrug efflux complexes. Proc. Natl. Acad. Sci. U S A. 2009, 106(38):16416-21. Zgurskaya, H.I. Multicomponent drug efflux complexes: architecture and mechanism of assembly. Future Microbiol. 2009, 4:919-32. Dhamdhere, G. and Zgurskaya, H.I. Metabolic shutdown in Escherichia coli cells lacking the outer membrane channel TolC. Mol. Micro. 2010, 77:743-754. Dhamdhere, G. Krishnamoorthy, G. and Zgurskaya, H.I. Interplay between drug efflux and antioxidants in Escherichia coli resistance to antibiotics. Antimicrob Agents Chemother. 2010, 54(12):5366-8. Tikhonova, E.B., Yamada, Y. and Zgurskaya, H.I. Sequential mechanism of assembly of multidrug efflux pump AcrAB-TolC. Chem. Biol. 2011, 18:454-463. Comment in Chem.Biol. 2011, 18:405-407. Modali, S.D. and Zgurskaya, H.I. The periplasmic membrane proximal domain of MacA acts as a switch in stimulation of ATP hydrolysis by MacB transporter. Mol. Micro. 2011, 81(4):937-51. Yamada, Y., Tikhonova, E.B. and Zgurskaya, H.I. YknWXYZ is an unusual four-component transporter with the indirect role in protection against SDP induced killing of Bacillus subtilis. J. Bacteriol. 2012, 194(16):4386-94. Zgurskaya, H.I., Krishnamoorthy, G., Ntreh, A., Lu, S. Mechanism and function of the outer membrane channel TolC in multidrug resistance and physiology of enterobacteria. Front. Microbiol. 2011, 2, 189. Bush K., Courvalin P, Dantas G, Davies J, Eisenstein B, Huovinen P, Jacoby GA, Kishony R, Kreiswirth BN, Kutter E, Lerner SA, Levy S, Lewis K, Lomovskaya O, Miller JH, Mobashery S, Piddock LJ, Projan S, Thomas CM, Tomasz A, Tulkens PM, Walsh TR, Watson JD, Witkowski J, Witte W, Wright G, Yeh P, Zgurskaya H.I. Tackling antibiotic resistance. Nat. Rev. Microbiol. 2011, 2011, 9(12):894-6. Lu S. and Zgurskaya H.I. Role of ATP binding and hydrolysis in assembly of MacAB-TolC macrolide transporter. Mol. Microbiol. 2012 Dec;86(5):1132-43. Sun Z., Tikhonova E.B., Zgurskaya H.I., Rybenkov V.V. Parallel lipoplex folding pathways revealed using magnetic tweezers. Biomacromolecules. 2012 Oct 8;13(10):3395-400. Krishnamoorthy G., Tikhonova E.B., Dhamdhere G., Zgurskaya H.I. On the role of TolC in multidrug efflux: the function and assembly of AcrAB-TolC tolerate significant depletion of intracellular TolC protein. Mol. Microbiol. 2013 Mar;87(5):982-97 Tikhonova E.B. and Zgurskaya H.I. Assessment of multidrug efflux assemblies by surface plasmon resonance. Methods Mol Biol. 2013, 966:133-55. Lu S. and Zgurskaya H.I. MacA, a periplasmic membrane fusion protein of the macrolide transporter MacAB-TolC, binds lipopolysaccharide core specifically and with high affinity. J. Bacteriol. 2013 Nov;195(21):4865-72. Sun Z., Tikhonova E.B., Zgurskaya H.I., Rybenkov V.V. Parallel lipoplex folding pathways revealed using magnetic tweezers. Biomacromolecules. 2012 Oct 8;13(10):3395-400. Krishnamoorthy G., Tikhonova E.B., Dhamdhere G., Zgurskaya H.I. On the role of TolC in multidrug efflux: the function and assembly of AcrAB-TolC tolerate significant depletion of intracellular TolC protein. Mol. Microbiol. 2013 Mar;87(5):982-97 Tikhonova E.B. and Zgurskaya H.I. Assessment of multidrug efflux assemblies by surface plasmon resonance. Methods Mol Biol. 2013, 966:133-55. Lu S. and Zgurskaya H.I. MacA, a periplasmic membrane fusion protein of the macrolide transporter MacAB-TolC, binds lipopolysaccharide core specifically and with high affinity. J. Bacteriol. 2013 Nov;195(21):4865-72. Yang, L., Lu, S, Belardinelli, J., Huc-Claustre, E., Jones, V., Jackson, M., Zgurskaya, H.I. RND transporters protect Corynebacterium glutamicum from antibiotics by assembling the outer membrane. MicrobiologyOpen, 2014, 3(4):484-96