| Isolation and characterization of senescent Cryptococcus neoformans and implications for phenotypic switching and pathogenesis in chronic cryptococcosis. | |
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MedLine Citation:
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PMID: 19411622 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although several virulence factors and associated genes have been identified, the mechanisms that allow Cryptococcus neoformans to adapt during chronic infection and to persist in immunocompromised hosts remain poorly understood. Characterization of senescent cells of C. neoformans demonstrated that these cells exhibit a significantly enlarged cell body and capsule but still cross the blood-brain barrier. C. neoformans cells with advanced generational age are also more resistant to phagocytosis and killing by antifungals, which could promote their selection during chronic disease in humans. Senescent cells of RC-2, a C. neoformans strain that undergoes phenotypic switching, manifest switching rates up to 11-fold higher than those of younger cells. Infection experiments with labeled cells suggest that senescent yeast cells can potentially accumulate in vivo. Mathematical modeling incorporating different switching rates demonstrates how increased switching rates promote the emergence of hypervirulent mucoid variants during chronic infection. Our findings introduce the intriguing concept that senescence in eukaryotic pathogens could be a mechanism of microevolution that may promote pathoadaptation and facilitate evasion of an evolving immune response. |
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Authors:
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Neena Jain; Emily Cook; Immaculata Xess; Fahmi Hasan; Dietrich Fries; Bettina C Fries |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-05-01 |
Journal Detail:
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Title: Eukaryotic cell Volume: 8 ISSN: 1535-9786 ISO Abbreviation: Eukaryotic Cell Publication Date: 2009 Jun |
Date Detail:
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Created Date: 2009-06-05 Completed Date: 2009-08-06 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 101130731 Medline TA: Eukaryot Cell Country: United States |
Other Details:
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Languages: eng Pagination: 858-66 Citation Subset: IM |
Affiliation:
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Department of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, NY 10461, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aging Animals Antifungal Agents / pharmacology Cryptococcosis / immunology, microbiology* Cryptococcus neoformans / drug effects, isolation & purification, pathogenicity*, physiology* Humans Male Mice Mice, Inbred BALB C Phagocytosis Phenotype |
| Grant Support | |
ID/Acronym/Agency:
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AI 051519/AI/NIAID NIH HHS; AI059681-05/AI/NIAID NIH HHS; D43-TW001403/TW/FIC NIH HHS; R01 AI059681-05/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antifungal Agents |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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