Phenotypic switching of Cryptococcus neoformans occurs in vivo and influences the outcome of infection

Phenotypic switching has been linked to the virulence of many pathogens, including fungi. However, it has not been conclusively shown to occur in vivo or to influence the outcome of infection. Cryptococcus neoformans undergoes phenotypic switching in vitro to colony types that differ in their virule...

Full description

Saved in:
Bibliographic Details
Published in:The Journal of clinical investigation 2001-12, Vol.108 (11), p.1639-1648
Main Authors: Fries, B C, Taborda, C P, Serfass, E, Casadevall, A
Format: Article
Language:English
Subjects:
Animals
Chemokines - biosynthesis
Cryptococcosis - immunology
Cryptococcus neoformans - growth & development
Cryptococcus neoformans - immunology
Cryptococcus neoformans - pathogenicity
Cytokines - biosynthesis
Immunity, Cellular
Male
Mice
Mice, Inbred BALB C
Phagocytosis
Phenotype
Polysaccharides - chemistry
Virulence
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Phenotypic switching has been linked to the virulence of many pathogens, including fungi. However, it has not been conclusively shown to occur in vivo or to influence the outcome of infection. Cryptococcus neoformans undergoes phenotypic switching in vitro to colony types that differ in their virulence in mice. In this study, we asked whether C. neoformans undergoes phenotypic switching in vivo and whether this phenomenon contributes to virulence. By using a small inoculum to preclude the introduction of variants that had already switched during in vitro propagation, we demonstrated that in vivo switching to a mucoid phenotype occurred in two mice strains and was associated with a lethal outcome. Phenotypic switching resulted in changes of the capsular polysaccharide that inhibited phagocytosis by alveolar macrophages. This promoted a more vigorous inflammatory response and rapid demise. These data document in vivo switching in a fungus and associate this phenomenon with enhanced virulence and a lethal outcome. The importance of this finding is underscored by the increased likelihood of phenotypic switching in chronic cryptococcosis; thus this mechanism may account for the inability to eradicate the organism in immunocompromised hosts.
ISSN:0021-9738
DOI:10.1172/JCI13407