ESR2 – Adhesins from Burkholderia pseudomallei

Faculty of Biological Sciences, University of Leeds (UK)
This is a structural/functional biology project focused on understanding how trimeric autotransporter adhesins (TAAs) from Bukholderiafunction in virulence, and to identify effective ligands for diagnostics. The work will involve Identification of specific host targets for novel Bukholderia TAAs including BpaC, structures of BpaC with host ligands using crystallography and combined methods including cryoEm, and development of surface-based diagnostics against BpaC. This builds on our work on YadA, and E. coli immunoglobulin proteins (e.g. Leo et al. & Goldman, Structure 19, 1021-1030 (2011); Wright et al. & Goldman, Acta Crystallogr F 73, 101-108 (2017); Szczesny et al. PLoS Pathog. 4: e1000119 (2008); Kaiser et al. & Kempf Cell Microbiol 15, 759-778 (2012); Schmidgen et al. & Kempf, J. Bacteriol. 196, 2155-2165 (2014)). The project will involve secondments to other network partners to identify Bukholderiahost protein targets at the University of Frankfurt, and at bioMérieux to develop antibody-based diagnostics. The structures will also be used as the basis for the development of novel anti-adhesive strategies. Crystals will be studied at national and international synchrotrons.