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Infection and Immunity, January 2001, p. 115-122, Vol. 69, No. 1
Departments of
Genetics,1
Medicine,3
Microbiology,4 and Pharmacology
and Cancer Biology5 and the Howard
Hughes Medical Institute,2 Duke University
Medical Center, Durham, North Carolina 27710
Received 5 June 2000/Returned for modification 30 July
2000/Accepted 25 September 2000
Cryptococcus neoformans is a pathogenic
basidiomycete with a defined sexual cycle involving mating between
haploid yeast cells with a transient diploid state. C. neoformans occurs in four predominant serotypes (A, B, C, and D),
which represent different varieties or species. Rare clinical and
environmental isolates with an unusual AD serotype have been reported
and suggested to be diploid. We found by fluorescence-activated cell
sorter analysis that serotype AD strains are aneuploid or diploid. PCR
analysis with primers specific for serotype A or D alleles of the
CNA1, CLA4, and GPA1 genes revealed
that both alleles are often present in serotype AD strains. PCR
analysis with primers specific for genes in the MATa or
MAT
0019-9567/01/$04.00+0 DOI: 10.1128/IAI.69.1.115-122.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Serotype AD Strains of Cryptococcus
neoformans Are Diploid or Aneuploid and Are Heterozygous at the
Mating-Type Locus
mating-type loci revealed that serotype AD strains are heterozygous for the mating-type locus. Interestingly, in several
serotype AD strains, the MAT
locus was derived from the serotype D parent and the MATa locus was inherited from a
serotype A parent that has been thought to be extinct. Basidiospores
from a self-fertile serotype AD strain bearing the putative serotype A
MATa locus showed a very low viability (~5%), and no
fertile serotype A MATa strain could be recovered. Serotype
AD strains were virulent in a murine model. Hybrid AD strains could
readily be isolated following a laboratory cross between a serotype A strain and a serotype D strain. In summary, serotype AD strains of
C. neoformans are unusual aneuploid or diploid strains that result from matings between serotype A and D strains. Self-fertile isolates fail to undergo normal meiosis because of genetic divergence. Our findings further suggest that serotype A MATa strains
may exist in nature.
*
Corresponding author. Mailing address: Department of
Genetics, 322 CARL Bldg., Research Dr., Box 3546, Duke University
Medical Center, Durham, NC 27710. Phone: (919) 684-2824. Fax: (919)
684-5458. E-mail: heitm001{at}duke.edu.
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