Taxonomic group: fungi / Basidiomycota
(Phylum: Basidiomycota)
Organ / tissue: cell wallAssociated disease: infection due to Cryptococcus neoformans [ICD11:
XN3EH 
]
The structure was elucidated in this paperNCBI PubMed ID: 30459196Publication DOI: 10.1128/mBio.02087-18Journal NLM ID: 101519231Publisher: Washington, DC: American Society for Microbiology
Correspondence: Lodge JK <lodgejk
wustl.edu>
Institutions: Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA, Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, USA, Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri, USA
Chitin is an essential component of the cell wall of Cryptococcus neoformans conferring structural rigidity and integrity under diverse environmental conditions. Chitin deacetylase genes encode the enyzmes (chitin deacetylases [Cdas]) that deacetylate chitin, converting it to chitosan. The functional role of chitosan in the fungal cell wall is not well defined, but it is an important virulence determinant of C. neoformans Mutant strains deficient in chitosan are completely avirulent in a mouse pulmonary infection model. C. neoformans carries genes that encode three Cdas (Cda1, Cda2, and Cda3) that appear to be functionally redundant in cells grown under vegetative conditions. Here we report that C. neoformans Cda1 is the principal Cda responsible for fungal pathogenesis. Point mutations were introduced in the active site of Cda1 to generate strains in which the enzyme activity of Cda1 was abolished without perturbing either its stability or localization. When used to infect CBA/J mice, Cda1 mutant strains produced less chitosan and were attenuated for virulence. We further demonstrate that C. neoformans Cda genes are transcribed differently during a murine infection from what has been measured in vitro IMPORTANCE Cryptococcus neoformans is unique among fungal pathogens that cause disease in a mammalian host, as it secretes a polysaccharide capsule that hinders recognition by the host to facilitate its survival and proliferation. Even though it causes serious infections in immunocompromised hosts, reports of infection in hosts that are immunocompetent are on the rise. The cell wall of a fungal pathogen, its synthesis, composition, and pathways of remodelling are attractive therapeutic targets for the development of fungicides. Chitosan, a polysaccharide in the cell wall of C. neoformans is one such target, as it is critical for pathogenesis and absent in the host. The results we present shed light on the importance of one of the chitin deacetylases that synthesize chitosan during infection and further implicates chitosan as being a critical factor for the pathogenesis of C. neoformans.
chitosan, fungal virulence, catalytic site, cell wall localization, chitin deacetylase, metal binding site
Structure type: structural motif or average structure
Trivial name: chitosan
Compound class: O-polysaccharide, cell wall polysaccharide, glucan, polysaccharide
Contained glycoepitopes: IEDB_135813,IEDB_137340,IEDB_141807,IEDB_151531,IEDB_153212,IEDB_241099,IEDB_423114,IEDB_423150,SB_74,SB_85
Methods: virulence assays, DNA techniques, biological assays
Enzymes that release or process the structure: Cda1, Cda2, Cda3
Biosynthesis and genetic data: biochemical data, genetic data
Comments, role: maintains integrity of of the cell wall
Related record ID(s): 41561, 49132, 50301, 50303, 50304, 50307, 50308, 50310, 50311, 50314, 50315, 50317, 50319, 50320
NCBI Taxonomy refs (TaxIDs): 5207Reference(s) to other database(s): GTC:G97099AY
Show glycosyltransferases
There is only one chemically distinct structure:
Found 
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