Cas1p is a membrane protein necessary for the O-acetylation of the Cryptococcus neoformans capsular polysaccharide

The capsule is certainly the most obvious virulence factor for Cryptococcus neoformans. The main capsule constituents are glucuronoxylomannans (GXM). Several studies have focused on the structure and chemistry of the GXM comp onent of the capsule, yet little is known about the genetic basis of the ca psule construction. Using a monoclonal antibody specific to a sugar epitope , we isolated a capsule-structure mutant strain and cloned by complementati on a gene named CAS1 that codes for a putative membrane protein. Although n o sequence homology was found with any known protein in the different datab ases, protein analysis using the PROPSEARCH software classified Cas1p as a putative glycosyltransferase. Cas1p is a well-conserved evolutionary protei n, as we identified one orthologue in the human genome, one in the drosophi la genome and four in the plant Arabidopsis thaliana genome. Analysis of th e capsule structure after CASI deletion showed that it is required for GXM O-acetylation.