Isolation and Characterization of Senescent Cryptococcus neoformans and Implications for Phenotypic Switching and Pathogenesis in Chronic Cryptococcosis

• DOI: 10.1128/ec.00017-09
• Publication Date: 2009-05-02T00:45:08Z
• Authors: Neena Jain; Emily Cook; Immaculata Xess; Fahmi Hasan; Dietrich Fries; Bettina C. Fries
• Keywords: Phenotypic switching; Pathogenesis; Chronic infection

Although several virulence factors and associated genes have been identified, the mechanisms that allow Cryptococcus neoformans to adapt during chronic infection persist in immunocompromised hosts remain poorly understood. Characterization of senescent cells C. demonstrated these exhibit a significantly enlarged cell body capsule but still cross blood-brain barrier. with advanced generational age are also more resistant phagocytosis killing by antifungals, which could promote their selection disease humans. Senescent RC-2, strain undergoes phenotypic switching, manifest switching rates up 11-fold higher than those younger cells. Infection experiments labeled suggest yeast can potentially accumulate vivo. Mathematical modeling incorporating different demonstrates how increased emergence hypervirulent mucoid variants infection. Our findings introduce intriguing concept senescence eukaryotic pathogens be mechanism microevolution may pathoadaptation facilitate evasion an evolving immune response.