Bacterial cell wall architecture and dynamics

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Bacteria are able to assume a myriad of different shapes, a property governed by their cell wall. The cell wall is like an external skeleton not only required for shape determination but also for keeping the cell alive as it is able to withstand the considerable internal forces which would otherwise rupture the cell. The major structural element of the cell wall for most bacteria is a polymer called peptidoglycan (PG). PG is unique to the bacteria and is essential for keeping the bacteria alive. This importance of PG is illustrated by the incredibly wide use of cell wall antibiotics such as penicillin and vancomycin, which prevent PG production. PG is a single large, bag-like molecule that surrounds the cell and whilst very strong is also dynamic to allow the cells to grow and divide. Even though PG is chemically only made of relatively simple building blocks how these are assembled to produce an architecture able to fulfil the many functions of PG has remained largely elusive. We have used a high-resolution microscopy technique that has provided exciting new and unexpected information as to the architecture of the PG. Initially in the rod shaped bacterium Bacillus subtilis we have found cables of material running round the cylinder of the cell providing strength. Also where the cell divides, a complex plate of material is laid down in an apparent spiral. Our further work in the round bacterium Staphylococcus aureus has shown a very different architecture of whorls and small knobbles. It is these features, which allow the cells to solve their engineering problems of maintaining cell integrity whilst allowing growth. The proposed project will take an integrated approach across the biological, chemical and physical disciplines to determine the architecture of PG from the molecular to the cellular level. We will address fundamental questions in microbiology that lie at the heart of the ability of bacteria to grow and proliferate.