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Antimicrobial Agents and Chemotherapy, January 2005, p. 350-357, Vol. 49, No. 1
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.1.350-357.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Effects of Antifungal Interventions on the Outcome of Experimental Infections with Phenotypic Switch Variants of Cryptococcus neoformans

Bettina C. Fries,1* Emily Cook,1 Xiabo Wang,1 and Arturo Casadevall1,2

Departments of Medicine,1 Microbiology and Immunology, Albert Einstein College of Medicine, New York, New York2

Received 17 June 2004/ Returned for modification 3 August 2004/ Accepted 28 September 2004

In cryptococcal infection, phenotypic switching from a smooth to a mucoid variant can occur in vivo, producing variants with enhanced virulence that are subsequently selected and affect the outcome of infection. Here, we demonstrate that antifungal treatment of the chronically infected host can promote this phenomenon. Amphotericin B treatment reduces fungal burden less effectively in mucoid variant-infected than in smooth variant-infected mice. Consequently, amphotericin B treatment resulted in a more pronounced prolongation of survival in smooth variant-infected than in mucoid variant-infected mice (20 versus 42 days; P < 0.05). Administration of anticapsular monoclonal antibody mediated better protection in smooth variant-infected than in mucoid variant-infected mice, although a protective effect was not consistently observed at all doses. Most interestingly, both antifungal drug therapy and administration of anticapsular monoclonal antibody promoted the selection of mucoid variants in smooth variant-infected mice, a phenomenon manifested by a statistically higher percentage of mucoid colonies in smooth variant-infected mice than in nontreated control mice. This finding suggests that both chemotherapeutic and immunological antifungal interventions may promote the selection of the more virulent mucoid variant, which could affect the outcome of infection in chronically infected hosts.

* Corresponding author. Mailing address: Department of Medicine, Albert Einstein College of Medicine, Golding 702, 1300 Morris Park Ave., Bronx, New York 10461. Phone: (718) 430-2365. Fax: (718) 430-8701. E-mail: fries{at}aecom.yu.edu.

Antimicrobial Agents and Chemotherapy, January 2005, p. 350-357, Vol. 49, No. 1
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.1.350-357.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Jain, N., Cook, E., Xess, I., Hasan, F., Fries, D., Fries, B. C. (2009). Isolation and Characterization of Senescent Cryptococcus neoformans and Implications for Phenotypic Switching and Pathogenesis in Chronic Cryptococcosis. Eukaryot Cell 8: 858-866 [Abstract] [Full Text]  
  • Jain, N., Li, L., Hsueh, Y.-P., Guerrero, A., Heitman, J., Goldman, D. L., Fries, B. C. (2009). Loss of Allergen 1 Confers a Hypervirulent Phenotype That Resembles Mucoid Switch Variants of Cryptococcus neoformans. Infect. Immun. 77: 128-140 [Abstract] [Full Text]  
  • Guerrero, A., Fries, B. C. (2008). Phenotypic Switching in Cryptococcus neoformans Contributes to Virulence by Changing the Immunological Host Response. Infect. Immun. 76: 4322-4331 [Abstract] [Full Text]  
  • Jain, N., Li, L., McFadden, D. C., Banarjee, U., Wang, X., Cook, E., Fries, B. C. (2006). Phenotypic Switching in a Cryptococcus neoformans Variety gattii Strain Is Associated with Changes in Virulence and Promotes Dissemination to the Central Nervous System. Infect. Immun. 74: 896-903 [Abstract] [Full Text]  
  • Guerrero, A., Jain, N., Goldman, D. L., Fries, B. C. (2006). Phenotypic switching in Cryptococcus neoformans. Microbiology 152: 3-9 [Abstract] [Full Text]  
  • Jain, N., Wickes, B. L., Keller, S. M., Fu, J., Casadevall, A., Jain, P., Ragan, M. A., Banerjee, U., Fries, B. C. (2005). Molecular Epidemiology of Clinical Cryptococcus neoformans Strains from India. J. Clin. Microbiol. 43: 5733-5742 [Abstract] [Full Text]  


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