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© Institut Pasteur
Cryptococcus neoformans
Publication : Molecular microbiology

Systematic capsule gene disruption reveals the central role of galactose metabolism on Cryptococcus neoformans virulence

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Molecular microbiology - 01 May 2007

Moyrand F, Fontaine T, Janbon G

Link to Pubmed [PMID] – 17462022

Mol. Microbiol. 2007 May;64(3):771-81

The polysaccharidic capsule is the main virulence factor of Cryptococcus neoformans. It primarily comprised of two polysaccharides: glucuronoxylomannan (GXM, 88% of the capsule mass) and galactoxylomannan (GalXM, 7% of the capsule mass). We constructed a large collection of mutant strains in which genes potentially involved in capsule biosynthesis were deleted. We used a new post-genomic approach to study the virulence of the strains. Primers specific for unique tags associated with the disruption cassette were used in a real-time PCR virulence assay to measure the fungal burden of each strain in different organs of mice in multi-infection experiments. With this very sensitive assay, we identified a putative UDP-glucose epimerase (Uge1p) and a putative UDP-galactose transporter (Ugt1p) essential for C. neoformans virulence. The uge1Delta and ugt1Delta strains are temperature sensitive and do not produce GalXM but synthesize a larger capsule. These mutant strains (GalXM negative, GXM positive) are not able to colonize the brain even at the first day of infection whereas GXM-negative strains (GalXM positive) can still colonize the brain, although less efficiently than the wild-type strain.

http://www.ncbi.nlm.nih.gov/pubmed/17462022