Candida Infection Biology – fungal armoury, battlefields ... - FINSysB

Candida albicans cell wall dynamics
Carol A. Munro, Louise A. Walker, Keunsook Lee, David Stead, Laura
Selway, Alistair J.P. Brown and Neil A.R. Gow
Institute of Medical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, Scotland
The outer surface of Candida albicans is composed of chitin and glucan
polysaccharides and an exposed fibrillar layer, rich in highly mannosylated proteins.
The co-ordinated assembly of the cell wall is regulated by a network of signalling
pathways that ensure cellular integrity is maintained in response to intracellular and
extracellular signals. Treatment with sub-inhibitory concentrations of the
echinocandin antifungal drugs, which inhibit beta-1,3-glucan synthesis, results in
significant changes in the cell wall architecture due to activation of compensatory
chitin synthesis and alterations in the cell wall proteome. A number of proteins that
are covalently attached to the cell wall are carbohydrate- active enzymes involved
in modulating and forming cross-links between chitin and glucan. These proteins,
such as Phr1 and Crh11 are positively regulated in response to applied cell wall
and membrane stresses and mutations in cell wall related genes. Changes in the
fungal cell wall can in turn alter susceptibility to antifungal drugs in vitro as well as
in vivo.
The cell surface is the interface between host and fungus and a number of virulence
attributes are cell wall localised. Alterations in cell wall composition and architecture
are likely to impinge on pathogenesis and recognition by host’s immune cells. Using
transcript profiling, biochemical assays, glycoproteomics and SILAC (Stable Isotope
Labelling with Amino Acids in Cell Culture) we have started to catalogue quantitative
and qualitative changes in the cell wall in response to pharmacological and genetic
blockade of cell wall biosynthesis. In addition we are studying the phenotypes of a
library of strains that are overexpressing cell wall related genes in order to better
understand the cell wall phenome.
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