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Cryptococcus neoformans virulence is enhanced after growth in the genetically malleable host Dictyostelium discoideum
Judith N Steenbergen1, Joshua D Nosanchuk, Stephanie D Malliaris
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461,USA.
Abstract:
Cryptococcus neoformans is an encapsulated, environmental fungus that can cause life-threatening meningitis. Pathogenicity of C. neoformans for macrophages and vertebrate hosts may be a mechanism selected in evolution for protection against environmental predators. In this study, we investigated whether Dictyostelium discoideum could serve as an alternate host for C. neoformans. D. discoideum has a defined genetic system which provides significant advantages for the study of fungus-amoeba interactions. Our results show that D. discoideum is susceptible to infection with C. neoformans and that the interactions are similar to those described previously for this fungus with macrophages and Acanthamoeba castellanii. Acapsular C. neoformans cells did not replicate when coincubated with D. discoideum. However, incubation of acapsular C. neoformans with D. discoideum mutants defective in myosin VII synthesis resulted in infection, validating the concept that avirulent organisms can be virulent in impaired hosts even at the unicellular level. Phagocytosis of C. neoformans by D. discoideum could be inhibited with capsule-specific antibodies and various sugars. Passage of an encapsulated C. neoformans strain through D. discoideum cultures increased virulence and was accompanied by larger capsules and faster time to melanization. These results add to the evidence implicating soil ameboid predators as important factors for the maintenance of C. neoformans virulence in the environment and suggest that D. discoideum promises to be an extremely useful system for studying the interaction of C. neoformans with phagocytic cells.
Insights
Dictyostelium discoideum serves as a model host for Cryptococcus neoformans, revealing how environmental amoebas influence fungal virulence. Impaired amoeba mutants allowed infection by normally avirulent fungal strains.
Area of Science:
- Mycology
- Cell Biology
- Evolutionary Biology
Background:
- Cryptococcus neoformans causes life-threatening meningitis in humans.
- Its pathogenicity may be an evolutionary adaptation for protection against environmental predators.
- Soil amoeboid predators are implicated in maintaining C. neoformans virulence.
Purpose of the Study:
- To investigate Dictyostelium discoideum as an alternate host for C. neoformans.
- To explore fungus-amoeba interactions using D. discoideum's defined genetic system.
- To understand the role of phagocytic cells in C. neoformans virulence.
Main Methods:
- Coincubation of C. neoformans (encapsulated and acapsular) with D. discoideum wild-type and mutant strains.
- Inhibition assays using capsule-specific antibodies and sugars.
- Assessment of fungal virulence and capsule characteristics after passage through D. discoideum.
Main Results:
- D. discoideum is susceptible to C. neoformans infection, similar to macrophages.
- Acapsular C. neoformans did not replicate, but infected D. discoideum myosin VII mutants.
- Phagocytosis was inhibited by antibodies and sugars.
- Passage through D. discoideum increased C. neoformans virulence, capsule size, and melanization.
Conclusions:
- D. discoideum is a useful model for studying C. neoformans-phagocyte interactions.
- Avirulent fungal strains can become virulent in genetically impaired phagocytic hosts.
- Environmental amoebas play a role in maintaining C. neoformans virulence, impacting its evolution.