Cas1p Is a Membrane Protein Necessary for the O-acetylation of the Cryptococcus Neoformans Capsular Polysaccharide

Mol Microbiol. 2001 Oct;42(2):453-67. doi: 10.1046/j.1365-2958.2001.02651.x.

Abstract

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 component of the capsule, yet little is known about the genetic basis of the capsule construction. Using a monoclonal antibody specific to a sugar epitope, we isolated a capsule-structure mutant strain and cloned by complementation a gene named CAS1 that codes for a putative membrane protein. Although no sequence homology was found with any known protein in the different databases, protein analysis using the PROPSEARCH software classified Cas1p as a putative glycosyltransferase. Cas1p is a well-conserved evolutionary protein, as we identified one orthologue in the human genome, one in the drosophila genome and four in the plant Arabidopsis thaliana genome. Analysis of the capsule structure after CAS1 deletion showed that it is required for GXM O-acetylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Amino Acid Sequence
  • Animals
  • Carbohydrate Sequence
  • Cloning, Molecular
  • Cryptococcus neoformans / classification
  • Cryptococcus neoformans / enzymology*
  • Cryptococcus neoformans / genetics*
  • Cryptococcus neoformans / pathogenicity
  • Fungal Proteins / chemistry
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism
  • Genetic Complementation Test
  • Glycosyltransferases / chemistry
  • Glycosyltransferases / genetics
  • Glycosyltransferases / metabolism
  • Humans
  • Magnetic Resonance Spectroscopy
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Mutation / genetics
  • Polysaccharides / chemistry
  • Polysaccharides / metabolism*
  • Sequence Homology, Amino Acid
  • Serotyping
  • Virulence / genetics

Substances

  • Fungal Proteins
  • Membrane Proteins
  • Polysaccharides
  • Glycosyltransferases

Associated data

  • GENBANK/AF355592
  • GENBANK/AF355593
  • GENBANK/AF355594