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Journal of Bacteriology, September 1999, p. 5482-5488, Vol. 181, No. 17
Department of Pharmacology, Cornell
University Medical College, New York, New York
Received 2 April 1999/Accepted 16 June 1999
The major virulence factor of the pathogenic fungus
Cryptococcus neoformans is an extensive polysaccharide
capsule which surrounds the cell. Almost 90% of the capsule is
composed of a partially acetylated linear
0021-9193/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
A Unique
-1,3 Mannosyltransferase of the
Pathogenic Fungus Cryptococcus neoformans
-1,3-linked mannan
substituted with D-xylose and D-glucuronic
acid. A novel mannosyltransferase with specificity appropriate for a
role in the synthesis of this glucuronoxylomannan is active in
cryptococcal membranes. This membrane-associated activity transfers
mannose in vitro from GDP-mannose to an
-1,3-dimannoside acceptor,
forming a second
-1,3 linkage. Product formation by the transferase
is dependent on protein, time, temperature, divalent cations, and each
substrate. It is not affected by amphomycin or tunicamycin but is
inhibited by GDP and mannose-1-phosphate. The described activity is not
detectable in the model yeast Saccharomyces cerevisiae,
consistent with the absence of a similar polysaccharide structure in
that organism. A second mannosyltransferase from C. neoformans membranes adds mannose in
-1,2 linkage to the same dimannoside acceptor. The two activities differ in pH optimum and
cation preference. While the
-1,2 transferase does not have specificity appropriate for a role in glucuronoxylomannan synthesis, it
may participate in production of mannoprotein components of the
capsule. This study suggests two new targets for antifungal drug discovery.
*
Corresponding author. Present address: Department of
Molecular Microbiology, Washington University School of Medicine,
Campus Box 8230, 660 South Euclid Ave., St. Louis, MO 63110-1093. Phone: (314) 362-7059. Fax: (314) 747-2634. E-mail:
doering{at}borcim.wustl.edu.
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