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December 1998

Volume 178, Number 6
The Journal of Infectious Diseases 1998;178:1761–1766
© 1998 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/98/7806-0029$02.00
DOI: 10.1086/314521

Serial Isolates of Cryptococcus neoformans from Patients with AIDS Differ in Virulence for Mice

Bettina C. Fries and

Arturo Casadevall

Department of Medicine and Division of Infectious Disease, Montefiore Medical Center, and Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York

Serial isolates of Cryptococcus neoformans from patients with chronic infection can exhibit minor karyotype changes as a result of chromosome length polymorphism (CLP). This study investigated whether serial C. neoformans isolates with CLP from 4 patients with AIDS exhibited biologic and phenotypic differences. CLP permits the identification of serial isolates in murine mixed infection. The parameters studied were virulence in mice, capsule size, colony morphology, melanization, protease production, MICs of antifungal drugs, and growth rates in vitro. Two parameters of virulence in mice were studied: persistence in tissue and survival time after lethal infection. Serial C. neoformans isolates were shown to differ in ability to persist in vivo, virulence in a murine infection model, in vitro growth rates at 37°C, and capsule size. Melanin and protease production and MICs of antifungal drugs were comparable for serial isolates. These observations suggest microevolution of C. neoformans during human infection. This process may allow the fungal population to change, escape eradication by the immune system, and thus cause chronic infections.

Received 1 May 1998; revised 24 July 1998.

Reprints or correspondence: Dr. A. Casadevall, Dept. of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York 10461 ().

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  • Presented in part: 36th Interscience Conference on Antimicrobial Agents and Chemotherapy, New Orleans, September 1996 (abstract B049).

    Animal experiments were done according to the guidelines of the institute.

    Grant support: NIH (AI‐22774 and AI‐33142); Burroughs Wellcome Developmental Therapeutics Award; Howard Hughes postdoctoral fellowship grant (to B.C.F.).

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