Structural analysis of bacterial drug pumps
Transmembrane transport proteins constitute the cellular entry and exit points of various molecules, ions and nutrients. In prokaryotic cells, a substantial proportion of genes code for such transporter proteins further emphasising the dependence of bacterial life cycle on these molecules. In silico analysis revealed the presence of an unprecedented high number of putative multidrug resistance (MDR) efflux pumps in various pathogenic bacteria such as Bacillus cereus. Considering the function of MDR pumps in pumping out anti-microbial drugs, studying these membrane transport processes is very important to understanding their impact on microbial pathogenesis. With this in mind, scientists on the EU-funded BACMT (Functional and structural analysis of bacterial membrane transporters) project set out to investigate the structure-to-function relationship of membrane transport proteins and how they are evolutionarily related. Researchers characterised putative multidrug transporters that are conserved in more than 80 of the B. cereus pathogenic strains. In this context, they deleted several of these MDR efflux pump genes and compared the mutants to their respective wild-type strains. This work led to the discovery of new drug efflux pumps and an entirely new family of multidrug efflux pumps. In addition, they overexpressed these pumps in E. coli and studied their functional role. Taken together, the findings of the BACMT study provided invaluable insight into the role of drug efflux pumps in bacterial pathogenesis. The structural information could serve as the basis for the design of novel drugs or targeted treatments against pathogenic bacteria.
Keywords
Bacteria, drug efflux pumps, transmembrane transport proteins, multidrug resistance
