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PMID: 9843999 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Phenotypic switching in the human pathogenic fungus Cryptococcus neoformans is associated with changes in virulence and pulmonary inflammatory response in rodents.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 95 ·No. 25 ·1998-12-08 ·Pages 14967-72

Goldman DL, Fries BC, Franzot SP, Montella L, Casadevall A

Abstract

High-frequency reversible changes in colony morphology were observed in three strains of Cryptococcus neoformans. For one strain (SB4, serotype A), this process produced three colony types: smooth (S), wrinkled (W), and serrated (C). The frequency of switching between colony types varied for the individual colony transitions and was as high as 10(-3). Mice infected with colony type W died faster than those infected with other colony types. The rat inflammatory response to infection with colony types S, W, and C was C > S > W and ranged from intense granulomatous inflammation with caseous necrosis for infection with type C to minimal inflammation for infection with type W. Infection with the various colony types was associated with different antibody responses to cryptococcal proteins in rats. Analysis of cellular characteristics revealed differences between the three colony types. High-frequency changes in colony morphology were also observed in two additional strains of C. neoformans. For one strain (24067A, serotype D) the switching occurred between smooth and wrinkled colonies. For the other strain (J32A, serotype A), the switching occurred between mucoid and nonmucoid colonies. The findings indicate that C. neoformans undergoes phenotypic switching and that this process can affect virulence and host inflammatory and immune responses. Phenotypic switching may play a role in the ability of this fungus to escape host defenses and establish chronic infections.

MeSH Terms
Animals Cryptococcosis/microbiology Cryptococcus neoformans/genetics,growth & development,pathogenicity Humans Inflammation/microbiology Mice Phenotype Rats Virulence/genetics
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Goldman D L
Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY, USA. [email protected]
Fries B C
Franzot S P
Montella L
Casadevall A
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.95.25.14967
Email
[email protected]
Published
1998-12-08
Pages
14967-72
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC24559
Subset
IM
Grants
NIAID NIH HHS · R01 AI033142 · United States
NIAID NIH HHS · AI22774 · United States
NIAID NIH HHS · AI01300 · United States
NIAID NIH HHS · AI33142 · United States
NIAID NIH HHS · R37 AI033142 · United States
External Links
PubMed source DOI: 10.1073/pnas.95.25.14967 PMC Full Text View journal details
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