TY - JOUR
T1 - Serial isolates of Cryptococcus neoformans from patients with AIDS differ in virulence for mice
AU - Fries, B. C.
AU - Casadevall, A.
N1 - Funding Information:
Received 1 May 1998; revised 24 July 1998. 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.). Reprints or correspondence: Dr. A. Casadevall, Dept. of Medicine, Albert Einstein College of Medicine, 1300 Morris Park Ave., Bronx, New York 10461 (casadeva@aecom.yu.edu).
PY - 1998
Y1 - 1998
N2 - 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.
AB - 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.
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U2 - 10.1086/314521
DO - 10.1086/314521
M3 - Article
C2 - 9815230
AN - SCOPUS:0031737177
SN - 0022-1899
VL - 178
SP - 1761
EP - 1766
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -