Abstract

. This proposal will address the hypothesis that the distribution of isolates of C. neoformans among patients with AIDS is not random. Strains to be compared will be isolated globally from patients with AIDS, as well as patients without AIDS and sources in the environment. The project will evaluate DNA fingerprinting methods and analyze the distribution and relatedness of strains of C. neoformans, investigate the population genetics of C. neoformans by developing codominant genotypic markers, and identify genetic markers that signify clinically relevant properties, such as drug resistance or tissue tropisms. This research will explore the mechanisms whereby genetic traits may be exchanged among strains and the evolution of pathobiological phenotypes. The investigator believes that the results of this investigation will pertain to the biology of C. neoformans and provide useful tools to study the epidemiology, diagnosis and prevention of cryptococcosis. Practical methods will be developed to identify problematic strains in the clinical laboratory, which will facilitate the management of the disease in AIDS patients.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI025783-11
Application #
2671909
Study Section
AIDS and Related Research Study Section 5 (ARRE)
Project Start
1987-09-30
Project End
2000-03-31
Budget Start
1998-04-01
Budget End
2000-03-31
Support Year
11
Fiscal Year
1998
Total Cost
Indirect Cost

  Institution

Name
Duke University
Department
Genetics
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705

  Publications

Chen, Yuan; Farrer, Rhys A; Giamberardino, Charles et al. (2017) Microevolution of Serial Clinical Isolates of Cryptococcus neoformans var. grubii and C. gattii. MBio 8:
Chen, Yuan; Litvintseva, Anastasia P; Frazzitta, Aubrey E et al. (2015) Comparative analyses of clinical and environmental populations of Cryptococcus neoformans in Botswana. Mol Ecol 24:3559-71
Van Wyk, Marelize; Govender, Nelesh P; Mitchell, Thomas G et al. (2014) Multilocus sequence typing of serially collected isolates of Cryptococcus from HIV-infected patients in South Africa. J Clin Microbiol 52:1921-31
Litvintseva, Anastasia P; Mitchell, Thomas G (2012) Population genetic analyses reveal the African origin and strain variation of Cryptococcus neoformans var. grubii. PLoS Pathog 8:e1002495
Litvintseva, Anastasia P; Carbone, Ignazio; Rossouw, Jenny et al. (2011) Evidence that the human pathogenic fungus Cryptococcus neoformans var. grubii may have evolved in Africa. PLoS One 6:e19688
Miglia, Kathleen J; Govender, Nelesh P; Rossouw, Jenny et al. (2011) Analyses of pediatric isolates of Cryptococcus neoformans from South Africa. J Clin Microbiol 49:307-14
Hu, Guanggan; Wang, Joyce; Choi, Jaehyuk et al. (2011) Variation in chromosome copy number influences the virulence of Cryptococcus neoformans and occurs in isolates from AIDS patients. BMC Genomics 12:526
Byrnes 3rd, Edmond J; Bildfell, Robert J; Frank, Sheryl A et al. (2009) Molecular evidence that the range of the Vancouver Island outbreak of Cryptococcus gattii infection has expanded into the Pacific Northwest in the United States. J Infect Dis 199:1081-6
Lin, Xiaorong; Patel, Sweta; Litvintseva, Anastasia P et al. (2009) Diploids in the Cryptococcus neoformans serotype A population homozygous for the alpha mating type originate via unisexual mating. PLoS Pathog 5:e1000283
Litvintseva, Anastasia P; Mitchell, Thomas G (2009) Most environmental isolates of Cryptococcus neoformans var. grubii (serotype A) are not lethal for mice. Infect Immun 77:3188-95

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