This proposal aims to provide insight into the physiological function of lipoteichoic acid (LTA) in the two Gram-positive bacterial pathogens Listeria monocytogenes and Staphylococcus aureus. LTA is an essential component of the envelope in Gram-positive bacteria. While the chemical structure of this polymer was elucidated several decades ago, the key genetic determinants for its synthesis have been identified only recently. These genetic studies made it clear that LTA has a crucial function within the cell, as absence of LTA severely impairs bacterial growth; a cell that lacks LTA has an aberrant cell shape and does not form normal division septa, but the molecular mechanism underlying these defects is not understood. With the recently developed mutants in the LTA synthesis pathway, we can now begin to address these questions.
It is particularly intriguing that the absence of LTA on the outside of the cell influences the function and localization of FtsZ, the key cytoplasmic protein involved in the cell division process. However nothing is known about the molecular mechanism that links these two fundamental cellular processes. Upon consolidating my research group and with the experiments outlined in this application, I propose to investigate the molecular mechanism that links LTA synthesis with other fundamental cellular processes such as cell division and regulation of cell shape, provide insight into the structure and function of key enzymes involved in LTA synthesis, provide insight into the link between LTA synthesis and membrane lipid turnover and its functional consequences and determine the role of LTA as anchor for cell wall envelope proteins.
Funded under 7th FWP (Seventh Framework Programme)