Abstract

One of the determinants of antibiotic resistance in microorganisms is the activity of multidrug efflux pumps. These pumps are chromosomally encoded in bacterial strains and are conserved indicating their biological importance and fitness benefit. Bacterial efflux pumps confer resistance by extruding a wide range of substrates such as antibiotics, organic pollutants and bacterial metabolites, to name a few. In Gram-negative bacteria, dynamic tripartite assemblies span the multi-layered cell envelope which forms a protective barrier against hostile toxic compounds, and drive the efflux of noxious compounds that have managed to enter the cell. In this talk, I will present recent findings from my PhD research and how the integration of structural biochemistry and biophysical techniques such as high resolution cryoEM and cryoET complemented with cellular and functional assays is being used to establish a profound understanding of the mechanisms of efflux pumps. By using a plethora of experimental techniques from the molecular to the cellular scale, my main goal is to understand how these macromolecular structures operate within their functional environment and how to increase susceptibility of bacterial pathogens to antibiotics.