Cryptococcal cell morphology affects host cell interactions and pathogenicity.
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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.
Lung Diseases, Fungal
Mice, Inbred A
Reverse Transcriptase Polymerase Chain Reaction
Published Version (Please cite this version)10.1371/journal.ppat.1000953
Publication InfoOkagaki, 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.
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Chair, Department of Molecular Genetics and Microbiology
Signal transduction cascades regulating development and virulence of microorganisms Our research focuses on how cells sense their environment and communicate with other cells. We employ genetic and biochemical approaches to study two divergent single-celled eukaryotic organisms, the yeast Saccharomyces cerevisiae and the pathogenic fungus Cryptococcus neoformans. These organisms both grow as budding yeasts and appear quite similar, yet they have been diverging ov