Ben Luisi
Department of Biochemistry, University of Cambridge, UK
Structure and mechanism of bacterial multi-drug efflux pumps
Bacterial efflux pumps are nanomachines that contribute to multidrug resistance by actively transporting chemically diverse antimicrobials from the cell. In Gram-negative species, some of these pumps form multi-protein assemblies that span the cell envelope and drive the transport of substrates. We have obtained cryoEM structures of two representative multidrug pumps from Escherichia coli - one powered by ATP and the other by protonmotive force. The structural data provide detailed models for transport mechanisms of widely occurring efflux pump systems.
Selected references
- Du, D., Wang, Z., James, N.R., Voss, J.E., Klimont, E., Ohene-Agyei, T., Venter, H. Chiu, W. and Luisi, B.F. (2014). Structure of the AcrAB-TolC multidrug efflux pump. Nature 509, 512-515
- Wang, Z., Fan, G., Hryc, C.F., Blaza, J.N., Serysheva, I.I., Schmid, M.F., Chiu, W., Luisi, B.F., and Du, D. (2017) An allosteric transport mechanism for the AcrAB-TolC Multidrug Efflux Pump. eLife 6:e24905
- Fitzpatrick, A.W.P., Llabres, S., Neuberger, A., Blaza, J.N., Bai, X-C, Okada, U., Murakami, S., van Veen, H.W., Zachariae, U., Scheres, S.H.W, Luisi, B.F. and Du, D. (2017) Structure of the MacAB-TolC ABC-type tripartite multidrug efflux pump. Nature Microbiology 2:17070
- Harris, A., Wagner, M., Du, D., Raschka, S., Gohlke, H., Smits, S.H.J., Luisi, B.F., Schmitt, L. (2021) Structure and efflux mechanism of the yeast pleiotropic drug resistance transporter Pdr5. Nature Communications 12:5254
- Chen, M., Shi, X., Yu, Z., Fan, G., Serysheva, I.I., Baker, M.L., Luisi, B.F., Ludtke, S.J., Wang Z. (2021) In situ structure of the AcrAB-TolC efflux pump at subnanometer resolution. Structure 30, 107-113.e3
To be noted: Dr. Luisi will also give a seminar entitled "Dynamic ribonucleoprotein complexes in the control of bacterial gene expression" at the CBI LMGM at 3 pm (Contact: Dr. Hugo Lebrette).