The multifunctional role of MraY in bacterial cell wall biogenesis

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Bacteria have developed multiple barriers to protect themselves from attack by our immune system, antibiotics and external threat. As a bacterium grows and divides it requires a variety of pathways to transport and assemble this outer casing. Many of the building-blocks for constructing the outer cell surface are attached to a lipid carrier molecule, called a polyprenyl or C55P, for transport. Central to this study is determining how the C55P carrier molecule is then recycled to the cell interior for transport of further cell surface constituents. There are multiple candidate pathways for transport of the C55P carrier molecule back into the cell, but the precise molecular details of transport are still to be determined. As part of this study we will characterise the route for C55P recycling and hypothesise how this process may be inhibited. Our current hypothesis is that a protein, called MraY, is one of the candidates to fulfil this process, and therefore we would like to test this hypothesis with both computational and experimental biochemical methods. We will also contextualise this process, by showing the interactions made by the MraY protein and other components involved in cell wall biogenesis, including the cytoskeletal protein, MreB.We will apply our computational methods to breathe life into the static protein structures by permitting dynamic changes and also modelling the surrounding biological environment. We will use these methods to devise further hypotheses to test experimentally through biochemical approaches and microbiology assays.Knowledge of these interactions are important from the perspective of inhibiting these process through the development of novel antibiotics. By better understanding the precise details of these molecular systems, we can strategically design novel drug inhibitors and therefore developing innovative antibiotics that will enable us to treat otherwise drug-resistant infections.