Assembly of Multi-Drug Transport Proteins: A Fundamental Aspect of Antibiotic Resistance of Pathogenic Bacteria

The resistance of pathogenic bacteria to antibiotics is a major worldwide problem. Bacterial efflux pumps are a main cause of this antibiotic resistance. These are membrane proteins that act as multi-drug transporters and pump a wide variety of antibiotics out of bacterial cells, and quickly adapt to recognise new antibiotics. <P>
We propose to study the folding and assembly of the family of small multi-drug transport proteins (SMRs), focusing on the proteins from Escherichia coli (EmrE), Mycobacterium tuberculosis (TBsmr) and Pseudomonas aeruginosa (PAsmr). Understanding how they fold to recognise a diverse array of drugs is crucial to understanding their multi-drug function, as well as for future studies designing effective inhibitors.