Cas3p Belongs to a Seven-Member Family of Capsule Structure Designer Proteins

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Abstract
The polysaccharide capsule is the main virulence factor of the basidiomycetous yeast Cryptococcus neoformans . Four genes ( CAP10 , CAP59 , CAP60 , and CAP64 ) essential for capsule formation have been previously identified, although their roles in the biosynthetic pathway remain unclear. A genetic and bioinformatics approach allowed the identification of six CAP64 -homologous genes, named CAS3 , CAS31 , CAS32 , CAS33 , CAS34 , and CAS35 , in the C. neoformans genome. This gene family is apparently specific in a subclass of the basidiomycete fungi. Single as well as double deletions of these genes in all possible combinations demonstrated that none of the CAP64 -homologous genes were essential for capsule formation, although the cas35Δ strains displayed a hypocapsular phenotype. The chemical structure of the glucuronomannan (GXM) produced by the CAS family deletants revealed that these genes determined the position and the linkage of the xylose and/or O -acetyl residues on the mannose backbone. Hence, these genes are all involved in assembly of the GXM structure in C. neoformans .