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Infection and Immunity, February 2006, p. 896-903, Vol. 74, No. 2
0019-9567/06/$08.00+0     doi:10.1128/IAI.74.2.896-903.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Phenotypic Switching in a Cryptococcus neoformans Variety gattii Strain Is Associated with Changes in Virulence and Promotes Dissemination to the Central Nervous System

Department of Microbiology, All India Institute of Medical Sciences, New Delhi, India,¹ Microbiology and Immunology,² Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461³

Received 6 September 2005/ Returned for modification 31 October 2005/ Accepted 8 November 2005

This is the first report of a Cryptococcus neoformans var. gattii strain (serotype B) that switches reversibly between its parent mucoid (NP1-MC) colony morphology and a smooth (NP1-SM) colony morphology. Similar to C. neoformans var. grubii and C. neoformans var. neoformans strains, the switch is associated with changes in the polysaccharide capsule and virulence in animal models. In murine infection models, NP1-MC is significantly more virulent than NP1-SM (P < 0.021). In contrast to the serotype A and D strains, the serotype B strain switches in vivo reversibly between both colony morphologies. The polysaccharide of NP1-MC exhibits a thicker capsule, and thus NP1-MC exhibits enhanced intracellular survival in macrophages. Consistent with this finding, switching to the mucoid variant is observed in pulmonary infection with NP1-SM. In contrast, the thin polysaccharide capsule of NP1-SM permits better crossing of the blood-brain barrier. In this regard, only smooth colonies were grown from brain homogenates of NP1-MC-infected mice. Our findings have important implications for the pathogenesis of cryptococcosis and suggest that phenotypic switching affects host-pathogen interactions in the local microenvironment. This altered interaction then selects for specific colony variants to arise in a pathogen population.

Editor: J. L. Flynn

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