Cryptococcal cell morphology affects host cell interactions and pathogenicity.
Abstract
Cryptococcus neoformans is a common life-threatening human fungal pathogen. The size
of cryptococcal cells is typically 5 to 10 microm. Cell enlargement was observed in
vivo, producing cells up to 100 microm. These morphological changes in cell size affected
pathogenicity via reducing phagocytosis by host mononuclear cells, increasing resistance
to oxidative and nitrosative stress, and correlated with reduced penetration of the
central nervous system. Cell enlargement was stimulated by coinfection with strains
of opposite mating type, and ste3aDelta pheromone receptor mutant strains had reduced
cell enlargement. Finally, analysis of DNA content in this novel cell type revealed
that these enlarged cells were polyploid, uninucleate, and produced daughter cells
in vivo. These results describe a novel mechanism by which C. neoformans evades host
phagocytosis to allow survival of a subset of the population at early stages of infection.
Thus, morphological changes play unique and specialized roles during infection.
Type
Journal articleSubject
AnimalsBlood-Brain Barrier
Blotting, Western
Brain
Bronchoalveolar Lavage
Cell Adhesion
Cell Proliferation
Cryptococcosis
Cryptococcus neoformans
Female
Flow Cytometry
Humans
Lung Diseases, Fungal
Mice
Mice, Inbred A
Oxidative Stress
Phagocytosis
Ploidies
RNA, Messenger
Receptors, Pheromone
Reverse Transcriptase Polymerase Chain Reaction
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https://hdl.handle.net/10161/4602Published Version (Please cite this version)
10.1371/journal.ppat.1000953Publication Info
Okagaki, Laura H; Strain, Anna K; Nielsen, Judith N; Charlier, Caroline; Baltes, Nicholas
J; Chrétien, Fabrice; ... Nielsen, Kirsten (2010). Cryptococcal cell morphology affects host cell interactions and pathogenicity. PLoS Pathog, 6(6). pp. e1000953. 10.1371/journal.ppat.1000953. Retrieved from https://hdl.handle.net/10161/4602.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Joseph Heitman
Chair, Department of Molecular Genetics and Microbiology
Joseph Heitman was an undergraduate at the University of Chicago (1980-1984), graduating
from the BS-MS program with dual degrees in chemistry and biochemistry with general
and special honors. He then matriculated as an MD-PhD student at Cornell and Rockefeller
Universities and worked with Peter Model and Norton Zinder on how restriction enzymes
recognize specific DNA sequences and how bacteria respond to and repair DNA breaks
and nicks. Dr. Heitman moved as an EMBO long-term fellow to the Bi

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