Analysis of peptidoglycan architecture in Gram positive bacteria

The outer cell wall of bacteria is essential to hold the cells together and gives them their characteristic shapes. Peptidoglycan is the structural material responsible for maintaining cellular integrity for most bacteria and its synthesis is the site of action of some of the most important antibiotics (such as penicillin). Peptidoglycan is made of strands of sugars linked together by strings of amino acids. The structure of peptidoglycan is dynamic to allow for cell growth, division and many other features. Surprisingly we do not know how the chemical structure of the peptidoglycan leads to its final architecture, which of course is necessary for its essential functions. The project will take an integrated approach to determine the length of the sugar strands in the peptidoglycan and how this is involved in the ability of the polymer to maintain its role. The project will address a fundamental area of microbiology.

Bacterial cell wall peptidoglycan is essential for the maintenance of cellular viability and shape determination for most eubacteria. Peptidoglycan is a polymer of glycan strands cross-linked via peptide sidechains. It is a dynamic structure being synthesised, modified and hydrolysed to allow for cell growth, division and many other important cellular features. Even though we understand a lot about the chemical structure of peptidoglycan, how this translates to the final architecture (and thus its stress bearing properties) is largely unknown. Recently measurement of the crucial glycan strand length parameter (in Staphylococcus aureus and Escherichia coli) has suggested very short chains (mostly <30 disaccharides). However our results from B. subtilis have surprisingly revealed a wide range of strand lengths including some very long indeed (>500 disaccharides). The project will analyse the role of glycan strand length and its dynamics in B. subtilis, S. aureus and other Gram positive organisms. A range of complementary approaches will determine how peptidoglycan structural parameters lead to the architecture, which is responsible for cellular morphology and integrity.