Elucidation of the role of peptide transporters in intrinsic resistance to beta-lactam antibiotics

The resistance of bacteria to antibiotics is a massive issue facing mankind, that threatens our ability to control infectious disease. While much of this resistance is mediated by genes that can move about to confer a specific modification or removal of the antibiotic, there are many native host genes that influence the intrinsic level of resistance to antibiotics. The ability of beta-lactam antibiotics like penicillin to function is based on their chemical structure that mimics that of a peptide found in the cell wall. This peptide-like structure is also what enables them to be efficiently taken up in our gut cells when we take the antibiotic. This is mediated by human peptide transporters that are involved in uptake and systemic dissemination of the antibiotic around the body. In the Thomas lab we have studied a range of bacterial transporters, including peptide transporters, and have data that suggests that these transporters might have a role in intrinsic resistance to beta-lactams, through the rapid uptake of beta-lactams into the cell and removal from their site of action in the periplasm. In this project the student will investigate this hypothesis and the roles of diverse peptide transporters in this process, in E. coli, Salmonella Typhimurium and Staphylococcus aureus, whilst also learning more generally about the physiological role of these transporters in bacteria. The project will include a range of bacterial genetic methods, growth experiments combined with some protein biochemistry where relevant. The project will provide insight into bacterial transport function and potentially undercover a previously unappreciated route for modulating the susceptibility of bacteria to beta-lactam antibiotics.