Cell wall alpha-1,3-glucan is required to anchor the Cryptococcus neoformans capsule.
Cryptococcus neoformans is an opportunistic pathogen responsible for serious disease in humans. Critical for virulence of this fungus is an elaborate polysaccharide capsule, which impedes the host immune response. We found that association of the capsule with the cell requires a specific component of the cell wall, alpha-1,3-glucan. Post-transcriptional inhibition of alpha-1,3-glucan synthase expression, using double-stranded RNA interference, yields cells that are unable to assemble a capsule although they generate its polysaccharide components. The resulting cryptococci are slow-growing and acapsular. This finding demonstrates a novel mode of polysaccharide attachment and an important application of RNA interference in fungi. The elimination of the capsule by reducing the expression of a single gene suggests a potential avenue for antifungal chemotherapy.
Reese
Amy J
AJ
Department of Molecular Microbiology, Washington University School of Medicine, Campus Box 8230, 660 South Euclid Avenue, St Louis, MO 63110-1093, USA.
Doering
Tamara L
TL
D000595:Amino Acid Sequence; D002473:Cell Wall / Q000737:chemistry*; D003455:Cryptococcus neoformans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity; D005936:Glucans / Q000737:chemistry / Q000378:metabolism*; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D034622:RNA Interference; D016415:Sequence Alignment
D005936:Glucans; C045788:alpha-1,3-glucan; C036655:1,3-alpha-D-glucan synthase; D005964:Glucosyltransferases; D006026:Glycoside Hydrolases