Date of Award

1-1-2009

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Biomedical Sciences

Content Description

1 online resource (xiv, 302 pages) : illustrations (some color), map.

Dissertation/Thesis Chair

Vishnu Chaturverdi

Committee Members

Steve Hanes, Thomas Begley, Sudha Chaturvedi, Andre Melendez

Keywords

Cryprococcus gattii, environmental niche, geographic distribution, Laccase, microtubes, virulence, Cryptococcus, Cryptococcus neoformans

Subject Categories

Ecology and Evolutionary Biology | Microbiology | Molecular Biology

Abstract

Four serotypes of Cryptococcus are responsible for most human and animal infections. C. gattii , serotype B and C, are the primary the causative agent of cryptococcosis in immune competent individuals whilst, C. neoformans var. neoformans serotype D, and C. neoformans var. grubii serotype A are most prevalent in immunocompromised hosts world-wide. C. gattii is recognized as a species distinct from C. neoformans based on differences in clinical manifestations, morphology, biological characteristics, and environmental niche. We used the plant model Arabidopsis thaliana plants and plant derived substrates as a model to explore C. gattii interactions in its ecological niche. C. gattii is distinguished from C. neoformans by the formation of distinct microtube structures during association with A. thaliana plants. Robust colonization of A. thaliana and microtube formation by C. gattii was found to require the transcriptional factor STE12α ,and CAP59but not the laccase 1 (LAC1) gene. The role of the transcriptional factor STE12 was consistent with known roles in the colonization of wood and reduced virulence in the mouse model system. Microtubes appeared as tube-like structures 0.04-0.1 μm in width and 0.5-3.0 μm in length, which terminate in a bulb-like structure. The central channel of the microtube appears continuous with cell cytoplasma and can contain vesicle-like bodies. C. gattii cells that formed microtubes as a result of association with plant matter were significantly more virulent in murine models of pulmonary and systematic cryptococcosis and more resistant to killing by human neutrophils in vitro. We suggest microtube formation is a structural adaptation for cell-cell and cell-host interaction. Such a distinct adaptation of C. gattii could play roles in its pronounced environmental association with trees and enhance virulence in mammalian hosts in comparison to C. neoformans. We propose C. gattii is a globally established pathogen with a specialized ecological niche on trees based on accumulation of reports on its wide spread temperate isolation from clinical, veterinary and environmental samples, array of dispersal mechanisms, and distinct formation of microtubes during association with plants or plant matter.

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