Microbiology, molecular Biology, biochemistry, infection

Modification of the bacterial cell wall is one of the most fundamental processes that bacteria use to adapt and to survive in changing environmental conditions. The ability to modify the bacterial cell wall, which is a essential component of the bacterial cell envelope, through modification and decoration is a key adaptation that bacteria use to avoid host defences (such as hydrolytic enzymes) and enhance survival in host cells. These modifications can be highly complicated such as the covalent and non-covalent attachment of proteins, lipids and polysaccharides. Important human pathogens such as Corynebacterium and Mycobacterium have taken cell wall decoration to extraordinary levels with the attachment of highly specialised mycolic acids, arabinomannan, glycolipids and proteins, which have been relatively well studied in these organisms (sometimes referred to as the Mycolata). Some of these components, such as the mycolic acids are vital components and are essential for pathogenicity and in some cases viability. Other modifications of cell wall polymers such as N-deacetylations have received relatively little attention. It is these that will be the focus of this project, where will investigate the role of cell wall deacetylases in the growth and pathogenicity of Corynebacterium diphtheriae. We will also investigate the enzymology of the C. diphtheriae enzyme to elucidate its substrate and co-factor specificity.    

molecular genetics, protein biochemistry, enzymology, microscopy 

•  Blair, D. E., Schüttelkopf, A. W., MacRae, J. I., & van Aalten, D. M. F. (2005). Structure and metal-dependent mechanism of peptidoglycan deacetylase, a streptococcal virulence factor. Proceedings of the National Academy of Sciences of the United States of America, 102, 15429-15434.
• Boneca, I. G., Dussurget, O., Cabanes, D., Nahori, M.-A., Sousa, S., Lecuit, M., et al. (2007). A critical role for peptidoglycan N-deacetylation in Listeria evasion from the host innate immune system. Proceedings of the National Academy of Sciences of the United States of America, 104, 691-692.