Molecular Microbiology

Prof S Foster

Research in my laboratory centres on 2 main themes associated with the bacterial molecular physiology:

The pathogen Staphylococcus aureus

S. aureus is a major cause of death and disease in humans. The spread of antibiotic resistance (MRSA, VRSA) highlights its importance. Our research has taken a number of approaches to understand the pathogenesis of the organism and to develop new prophylactic and treatment regimes. Research is aimed at determining how S. aureus interacts with its host. In particular we have been determining the role of human innate defences in the control of S. aureus. We have also identified a number of potential novel targets to be exploited as vaccine components. The role and use of these for prophylaxis are the subject of current investigations.

Bacterial cell wall structure and function

The cell wall peptidoglycan is essential for the life of most bacteria and its synthesis is the target of such important antibiotics as penicillin and vancomycin. We are using atomic force microscopy and other interdisciplinary techniques to determine the architecture of the peptidoglycan across the bacteria. In the model Gram-positive organism, Bacillus subtilis this has revealed a hitherto unexpected complexity of cables of material. Such discoveries begin to determine the fundamental principles of cell wall growth and division.

Figure Legend - Bacterial cell wall architecture (atomic force microscopy reveals new features leading to a novel model of bacterial cell wall architecture; see Hayhurst et al. (2008) Proc. Natl. Acad. Sci. 105, 14603)

Selected Publications

Cooper, E.L., Garcia-Lara, J. and Foster, S.J. (2009) YsxC, an essential protein in Staphylococcus aureus crucial for ribosome assembly/stability. BMC Microbiology 9, 266

Gill, M.R., Garcia-Lara, J., Foster, S.J., Smythe, C., Battaglia, G. and Thomas, J.A. (2009) A ruthenium(II) polypyridyl complex for direct imaging of DNA structure in living cells. Nature Chemistry. 1, 662-667.

Clarke, S.R., Andre, G., Walsh, E.J., Dufrêne, Y.F., Foster, T.J. and Foster, S.J. (2009) Iron-regulated surface determinant protein A (IsdA) mediates adhesion of Staphylococcus aureus to human corneocyte envelope proteins. Infection and Immunity 77, 2408-2416.

von Kockritz-Blickwede, M., Rohde, M., Oehmcke, S., Miller, L.S., Cheung, A.L., Herwald, H., Foster, S. and Medina, E. (2008) Immunological mechanisms underlying the genetic predisposition to severe Staphylococcus aureus infection in the mouse model. American Journal of Pathology 173, 1657-1668.

Hayhurst, E.J., Kailas, L., Hobbs, J.K. and Foster, S.J. (2008) Cell wall peptidoglycan architecture in Bacillus subtilis. Proceedings of the National Academy of Science USA 105, 14603-14608.

Prajsnar, T.K., Cunliffe, V.T., Foster, S.J. and Renshaw, S.A. (2008) A novel vertebrate model of Staphylococcus aureus infection reveals phagocyte-dependent resistance of zebrafish to non-host specialized pathogens. Cellular Microbiology 10, 2312-2325.

Clarke, S.R. and Foster, S.J. (2008) IsdA protects Staphylococcus aureus against the bactericidal protease activity of apolactoferrin. Infection and Immunity 76, 1518-1526.

Stapleton, M.R., Horsburgh, M.J., Hayhurst, E.J., Wright, L., Jonsson, I.M., Tarkowski, A.,Kokai-Kun, J.F., Mond, J.J. and Foster, S.J. (2007) Characterisation of IsaA and SceD, two putative lytic transglycosylases of Staphylococcus aureus. Journal of Bacteriology 189, 7316-7325

Clarke, S.R., Mohamed, R., Bian, L., Routh, A.F., Kokai-Kun, J., Mond, J.J., Tarkowski, A. and Foster S.J. (2007) The Staphylococcus aureus surface protein IsdA mediates resistance to innate defenses of human skin. Cell Host and Microbe 1, 199-212.

Cosgrove, K., Coutts, G., Jonsson, I.M., Tarkowski, A., Kokai-Kun, J.F., Mond, J.J. and Foster, S.J. (2007) Catalase (KatA) and alkyl hydroperoxide reductase (AhpC) have compensatory roles in peroxide stress resistance and are required for survival, persistence, and nasal colonization in Staphylococcus aureus. Journal of Bacteriology 189, 1025-1035.

Pourmand, M.R., Clarke, S.R., Schuman, R.F., Mond, J.J. and Foster, S.J. (2006) Identification of antigenic components of Staphylococcus epidermidis expressed during human infection. Infection and Immunity 74, 4644-4654.

Shaw, L.N., Aish, J. Davenport, J.E., Brown, M.C., Lithgow, J.K., Simmonite, K., Crossley, H., Potempa, J. and Foster, S.J. (2006) Investigations into sigmaB-modulated regulatory pathways governing extracellular virulence determinant production in Staphylococcus aureus. Journal of Bacteriology 188, 6070-6080.

Clarke, S.C., Brummell, K.J., Horsburgh, M.J., McDowell, P.W., Syed Mohamad, S.A., Stapleton, M.R., Avecedo, J., Read, R.C., Day, N.P.J., Peacock, S.J., Mond, J.J., Kokai-Kun, J.F. and Foster, S.J. (2006) Identification of in vivo-expressed antigens of Staphylococcus aureus and their use in vaccinations for protection against nasal carriage. Journal of Infectious Disease 193, 1098-1108.