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Multidrug Efflux in the Context of Two-Membrane Cell Envelopes

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Abstract

The trans-envelope drug efflux in Gram-negative bacteria demands assembly of specialized protein complexes that in addition to inner membrane transporters include periplasmic membrane fusion proteins and outer membrane channels due to the presence of a double membrane. These complexes are highly versatile and constitute a major antimicrobial resistance mechanism of Gram-negative bacteria. The modular organization of the tripartite assemblies in Gram-negative bacteria allows them to accommodate a wide array of multidrug efflux transporters enabling efflux across both the inner and the outer membranes of the cell envelope. This chapter focuses on the structures and mechanisms of trans-envelope multidrug efflux pumps from Gram-negative bacteria. We summarize the current state of the field and the emerging model for multidrug efflux in the context of two membranes.

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Acknowledgments

Studies in the Zgurskaya laboratory are sponsored by the Department of the Defense, Defense Threat Reduction Agency, and by the National Institute of Health (grant AI052293) in the USA. Studies in the Bavro laboratory are supported by funding from the Wellcome Trust and the Biotechnology and Biological Sciences Research Council, UK. The contents of this chapter do not necessarily reflect the position or the policy of the federal government, and no official endorsement should be inferred.

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Zgurskaya, H.I., Bavro, V.N., Weeks, J.W., Krishnamoorthy, G. (2016). Multidrug Efflux in the Context of Two-Membrane Cell Envelopes. In: Li, XZ., Elkins, C., Zgurskaya, H. (eds) Efflux-Mediated Antimicrobial Resistance in Bacteria. Adis, Cham. https://doi.org/10.1007/978-3-319-39658-3_5

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