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Functional and structural analysis of bacterial membrane transporters

Final Report Summary - BACMT (Functional and structural analysis of bacterial membrane transporters)

Membrane transport proteins play crucial roles in fundamental cellular processes and functions in all organisms. A substantial proportion of prokaryotic genes are predicted to encode membrane transporters, emphasizing the importance of transporters in their life styles. Of particular note, in silico analysis of sequenced Acinetobacter baumannii and Bacillus cereus group strains has revealed the presence of an unprecedented high number (more than 50 - 100) of putative multidrug resistance (MDR) efflux pumps in these pathogenic bacteria.
The current project is a collaboration between three Partners, two European (from Leeds and Oslo) and one from Australia (Sydney). The project aims to increase our knowledge about the membrane transport processes with regard to their role in microbial pathogenesis and resistance to antimicrobials. The project also aims to illuminate the evolutionary relatedness and structure-function relationship of membrane transport proteins.
The project has led to a number of high-impact outcomes and achievements. We have characterised the B. cereus putative multidrug transporters that are conserved in more than 80 sequenced strains of the B. cereus group strains, including B. anthracis and B. thuringiensis strains, as well as approximately half of the putative A. baumannii multidrug efflux pumps. Several of these MDR efflux pump genes have been deleted and the mutants compared to their respective wild-type strains or studied after cloning and expression in laboratory strains of E. coli. This work has led to the discovery of several new drug efflux pumps and an entirely new family of multidrug efflux pumps in A. baumannii and related bacterial species. Furthermore, the additional (native) functions of these proteins have been studied by various methods available compelementarily in the Partner laboratories. Detailed mechanisms of the efflux pumps have been studied after overexpression of these pumps in E. coli or by using purified protein, and increased knowledge of the importance of the efflux pumps in the native bacteria have been obtained.