Cell envelope synthesis in Gram positive bacteria: mechanisms, regulation and inhibition

Cell wall synthesis is a highly conserved process in bacteria, and crucial as both a target for our best antibiotics and a source of innate immune signals of infection. The wall defines the shape of bacteria but it is sculpted with the help of conserved cytoskeletal proteins, including MreB, FtsZ and DivIVA. The aim of this project is to study the spatial regulation of wall synthesis, especially cylindrical elongation, in the model Gram positive bacterium Bacillus subtilis. Several factors in wall synthesis appear to be redundant and we will attempt to resolve the adaptive basis for this redundancy, as well as solving specific questions on the function of cell elongation factors. In another major lineage of Gram positive bacteria, the Actinobacteria, cell elongation is achieved by a completely different mechanism involving tip growth and branching. Little is known about the evolutionary pathway leading to these contrasting strategies. We have identified and will undertake comparative studies of an unusual group of Firmicutes that appear to exhibit branching tip growth like actinobacteria. The results will not only enrich our understanding of wall synthesis in general but will also provide insights that we hope to exploit in the search for new antibiotics.