Candida albicans cell surface: regulation of the host-fungus interaction. (360G-Wellcome-080088_Z_06_Z)

The central hypothesis underpinning this programme is that the molecular architecture of the Candida albicans cell surface strongly influences virulence, immune recognition and disease causation by this major fungal pathogen of humans. In a previous programme grant we showed that cell wall glycosylation and other specific cell wall components are essential for the growth, virulence and the immune response to C. albicans. Also, we generated a comprehensive set of molecular tools and reagents to study the relationship between the cell surface and C. albicans pathogenesis. We will now establish how specific cell surface components influence pathogen recognition and disease, and how these components are regulated during growth, responses to environmental stresses and host invasion. We have four specific objectives: (1) to undertake a detailed functional analysis of O- and N-mannan assembly as a route to investigating the importance of these surface polymers in pathogenesis; (2) to understand the effects of altering surface mannoproteins upon virulence; (3) to determine the role of cell wall surface components in stimulating the innate immune response, and (4) to define the molecular plasticity of the cell surface in relation to changing microenvironments in vitro and in vivo.