Phenotypic switching in Cryptococcus neoformans

• Published in: Microbiology (Society for General Microbiology) Vol. 152; no. 1; pp. 3 - 9
• Main Authors: Guerrero, A, Jain, N, Goldman, D. L, Fries, B. C
• Format: Journal Article
• Language: English
• Published: Reading Soc General Microbiol 01.01.2006; Society for General Microbiology
• Subjects: Animals; Bacterial Capsules - metabolism; Biological and medical sciences; Chronic Disease; Cryptococcosis - microbiology; Cryptococcosis - physiopathology; Cryptococcus neoformans; Cryptococcus neoformans - genetics; Cryptococcus neoformans - growth & development; Cryptococcus neoformans - immunology; Cryptococcus neoformans - pathogenicity; Fundamental and applied biological sciences. Psychology; Genes, Bacterial; Genetic Variation; Growth, nutrition, metabolism, transports, enzymes. Molecular biology; Humans; Intracranial Pressure; Meningitis, Cryptococcal - microbiology; Meningitis, Cryptococcal - physiopathology; Mice; Microbiology; Mycology; Pathogenicity, host-agent relations, miscellaneous strains, epidemiology; Phagocytosis; Polysaccharides; Rats; Selection, Genetic; Virulence - genetics; Nervous system diseases; Yeast; Immune response; Cryptococcus neoformans; Selection; Virulence; Capsule; Switching; Fungi; Variant; Central nervous system disease; Meningitis; Fungi Imperfecti; Thallophyta
• ISSN: 1350-0872; 1465-2080
• DOI: 10.1099/mic.0.28451-0

1 Departments of Microbiology and Immunology at All India Institute of Medical Sciences, New Delhi, India 2 Department of Microbiology at All India Institute of Medical Sciences, New Delhi, India 3 Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY 10461, USA 4 Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USA Correspondence B. C. Fries fries{at}aecom.yu.edu Phenotypic switching has been described in serotype A and D strains of Cryptococcus neoformans . It occurs in vivo during chronic infection and is associated with differential gene expression and changes in virulence. The switch involves changes in the polysaccharide capsule and cell wall that affect the yeast's ability to resist phagocytosis. In addition, the phenotypic switch variants elicit qualitatively different inflammatory responses in the host. In animal models of chronic cryptococosis, the immune response of the host ultimately determines which of the switch variants are selected and maintained. The importance of phenotypic switching is further underscored by several findings that are relevant in the setting of human disease. These include the ability of the mucoid colony variant of RC-2 (RC-2 MC) but not the smooth variant (RC-2 SM) to promote increased intracerebral pressure in a rat model of cryptococcal meningitis. Furthermore, chemotherapeutic and immunological antifungal interventions can promote the selection of the RC-2 MC variant during chronic murine infection.