Final Report Summary - LISTA-LTA (A functional analysis of Listeria and Staphylococcus lipoteichoic acid)
The project funded by this grant aimed 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 has been 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 and a cell that lacks LTA has an aberrant cell shape and does not divide properly. The aims of this study were to investigate the physiological function of LTA, provide insight into the structure and function of enzymes involved in LTA synthesis and identify and characterize novel factors involved in LTA synthesis. As part of this work, we have shown that LTA is also important for growth of clinically relevant community-acquired methicillin resistant S. aureus (CA-MRSA) strains and not only for laboratory strains as previously described. We have identified S. aureus strains that can bypass the need for LTA and this work led to the discovery of a new and essential signaling nucleotide in c-di-AMP in this organism. In addition to this, we have identified several new factors, which are involved in lipid and lipoteichoic acid synthesis. Taken together, information gained from this work might help us in the long run to development new antibiotics or device novel strategies to inhibit the growth of Gram-positive pathogens such as Staphylococcus aureus.