PATHOGENESIS AND THE CELL WALL PROTEOME OF THE FUNGAL PATHOGEN CANDIDA ALBICANS

We are studying the role of cell surface proteins of the major fungal pathogen Candida albicans. The incidence of fungal infections continues to rise and mortality rates remain up to 40 % despite treatment with an ever-increasing number of antifungal drugs. The surface of fungal pathogens is a dynamic structure called the cell wall. It is rich in proteins and polysaccharides that play important roles in infection ranging from adhesion to host cells to modulation of the host's immune response. The enzymes that synthesise or assemble the cell wall are unique to fungi and so are attractive targets for the development of antifungal therapies. We aim to identify novel proteins that contribute to virulence or are essential for the synthesis of a robust cell wall. Our main focus is the major class of proteins, which are chemically linked and integral to the fungal cell wall and can be predicted from their composite sequence of amino acids. We have highlighted, through genome-wide approaches, a set of 20 predicted cell wall proteins that are activated in response to conditions that damage the cell wall and therefore are predicted to be involved in cell wall remodelling. Defining the functions of cell wall proteins will help us understand fungal pathogenesis and the molecular mechanisms that are required to synthesis the highly complex fungal cell wall. In the long term this will aid the future development of therapies to fight fungal disease.