Assembly, architecture and recognition of bacterial adhesion and invasion complexes. (360G-Wellcome-079819_Z_06_Z)

Novel adhesion complexes (adhesins) from pathogenic bacteria play fundamental roles in colonising the host and propagating infection. Pathogenic bacteria express a variety of surface adhesions that often comprise polymeric structures that forming either filaments or amorphous sheaths. We propose to combine multi-disciplinary structural methods in order to gain a detailed understanding of three model filamentous, multimeric complexes: 1) The Afa/Dr family from pathogenic Escherichia coli, which are associated with both diarrhoeal and urinary tract infections. 2) Bundle forming pili (BFP), which are essential for localized adherence to epithelial cells, auto-aggregation and the full virulence of enteropathogenic E. coli. 3) The Fimbriae associated protein (Fap) from oral pathogen Streptococcus parasanguis, which is responsible for colonization of the oral cavity and formation of biofilms. We will propose functional models that will be tested independently with mutagenesis-driven function experiments.