Cryptococcus neoformans virulence is enhanced after growth in the genetically malleable host Dictyostelium discoideum

Judith N. Steenbergen, Joshua D. Nosanchuk, Stephanie D. Malliaris, Arturo Casadevall

Research output: Contribution to journalArticle

101 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)4862-4872
Number of pages11
JournalInfection and Immunity
Volume71
Issue number9
DOIs
StatePublished - Sep 1 2003

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Cryptococcus neoformans
Dictyostelium
Virulence
Growth
Fungi
Capsules
Macrophages
Acanthamoeba castellanii
Amoeba
Conservation of Natural Resources
Myosins
Phagocytes
Infection
Meningitis
Phagocytosis
Vertebrates
Soil
Maintenance

ASJC Scopus subject areas

  • Immunology

Cite this

Cryptococcus neoformans virulence is enhanced after growth in the genetically malleable host Dictyostelium discoideum. / Steenbergen, Judith N.; Nosanchuk, Joshua D.; Malliaris, Stephanie D.; Casadevall, Arturo.

In: Infection and Immunity, Vol. 71, No. 9, 01.09.2003, p. 4862-4872.

Research output: Contribution to journalArticle

Steenbergen, Judith N. ; Nosanchuk, Joshua D. ; Malliaris, Stephanie D. ; Casadevall, Arturo. / Cryptococcus neoformans virulence is enhanced after growth in the genetically malleable host Dictyostelium discoideum. In: Infection and Immunity. 2003 ; Vol. 71, No. 9. pp. 4862-4872.
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