Infection and Immunity, November 1999, p. 6076-6083, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Departments of Medicine,1 Pediatrics,2 and Microbiology and Immunology,4 Albert Einstein College of Medicine, Bronx, New York 10461, and Department of Chemistry, State University Georgia, LBCS, Atlanta, Georgia 303033
Received 16 April 1999/Returned for modification 19 June 1999/Accepted 26 August 1999
Cryptococcus neoformans strains exhibit variability in
their capsular polysaccharide, cell morphology, karyotype, and
virulence, but the relationship between these variables is poorly
understood. A hypovirulent C. neoformans 24067A
isolate, which usually produces smooth (SM) colony types, was found to
undergo phenotypic switching and to produce wrinkled (WR) and
pseudohyphal (PH) colony types at frequencies of approximately
10
4 to 10
5 when plated on Sabouraud agar.
Cells from these colony types had large polysaccharide capsules and PH
morphology, respectively. Scanning electron microscopy showed that
different colony types were the result of altered cellular packing in
the colony. Phenotypic switching was associated with quantitative and
qualitative changes in capsular polysaccharide. Specifically, the
glucuronoxylomannan (GXM) of the WR polysaccharide differed in the
proportion of structural reporter groups and in increased xylose
residue content linked at the 4 to 0 position. The relative virulence
of the colony types was WR > PH > SM, as measured by CFU in
rat lungs after intratracheal infection. Karyotype instability was
observed in strain 24067A and involved primarily two chromosomes.
Colonies with an alternative colony type exhibited more karyotype
changes, which did not revert to the original karyotype in reverted
colonies. In summary, this study revealed that phenotypic switching in
C. neoformans (i) can produce WR colonies consisting of
cells with either large capsule or PH morphology, (ii) is associated
with production of structurally different GXM, (iii) is commonly
associated with karyotype changes, (iv) can produce cells of PH
morphology, and (v) can increase the virulence of a strain. Hence,
phenotypic switching is an adaptive mechanism linked to virulence that
can generate cell types with very different biological characteristics.
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