Department of Structural Biology and Chemistry
TUESDAY 21 JANUARY 2020 at 2:00 pm
AUDITORIUM CENTRE F. JACOB room- CFJ RdC 17c
Dr. Olivier Lambert
Architecture de complexes membranaires et processus cellulaires
Antibiotic resistance and contribution of Multidrug Efflux Pumps: Structural and functional insights.
The dangerous increase of resistant pathogenic bacteria (including Enterococcus faecium, Staphylococcus aureu, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species), to most of available antibiotics emerges as a worldwide public health concern. It is urgent to develop original solution and focus on unconventional targets. Active efflux is one of the four main mechanisms by which bacteria exhibit resistance to antibiotic.
In Gram-negative bacteria, tripartite efflux pumps spanning the cell envelope can mediate the efflux of a wide variety of antimicrobial compounds, and participate to the antibiotic resistance. These efflux systems share a similar structural architecture composed of an inner membrane transporter and an outer membrane channel bridged by a periplasmic adaptor protein. The prototypical and clinically relevant efflux pump from Pseudomonas aeruginosa, MexAB-OprM is involved in the transport of drugs from the periplasm to the extracellular medium through the use of the proton gradient.
We have developed a method to reconstitute a tripartite assembly from native components using lipid nanodiscs. MexB and OprM inserted in lipid nanodisc self-assembled in the presence of MexA. The structure of tripartite system has been studied by electron microscopy . High resolution single particle cryo-EM analysis complemented with transport activity measurements shed new light on key factors eliciting the functional drug extrusion.
 Daury, L., Orange, F., Taveau, J. C., Verchère, A., Monlezun, L., Gounou, C., … & Lambert, O. (2016). Tripartite assembly of RND multidrug efflux pumps. Nature communications, 7.
Contact : Nadia Izadi-Pruneyre
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