Candida albicans is an opportunistic fungal pathogen that is the major cause of oropharyngeal candidiasis (OPC). This disease causes significant morbidity among AIDS patients, even since the advent of highly active antiretroviral therapy. OPC is treated primarily with azole antifungals, but the continuing problem of azole resistance has created a need for new antifungal strategies. Our goal is to identify new C. albicans virulence genes, which will hold promise as targets for these strategies. The ability of C. albicans to produce filamentous cells is associated with pathogenicity, and several C. albicans filamentation regulators have been found through approaches based on filamentation of Saccharomyces cerevisiae (baker's yeast). Filamentation is well defined in S. cerevisiae because of its facile genetic system, but the S. cerevisiae model is limited because it is seldom a pathogen, because it fails to produce true hyphae, and because it fails to respond to several inducers of filamentation for C. albicans. In fact, the major filamentation regulators defined with the S. cerevisiae model, Efg1p and Cph1p, are not essential for infection in a piglet OPC model. Our hypothesis is that there are C. albicans-specific filamentation regulatory genes that will be critical for pathogenicity in OPC, and our immediate objective is to find those genes. We will isolate homozygous random insertion mutations in C. albicans, identify those genes that alter filamentation control, and test defined mutants for pathogenicity in a murine OPC model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI050931-02
Application #
6511822
Study Section
Special Emphasis Panel (ZRG1-AARR-4 (01))
Program Officer
Duncan, Rory A
Project Start
2001-06-01
Project End
2006-04-30
Budget Start
2002-05-01
Budget End
2003-04-30
Support Year
2
Fiscal Year
2002
Total Cost
$297,512
Indirect Cost
Name
Columbia University (N.Y.)
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
167204994
City
New York
State
NY
Country
United States
Zip Code
10032
Chiang, Lisa Y; Sheppard, Donald C; Bruno, Vincent M et al. (2007) Candida albicans protein kinase CK2 governs virulence during oropharyngeal candidiasis. Cell Microbiol 9:233-45
Bruno, Vincent M; Kalachikov, Sergey; Subaran, Ryan et al. (2006) Control of the C. albicans cell wall damage response by transcriptional regulator Cas5. PLoS Pathog 2:e21
Bruno, Vincent M; Mitchell, Aaron P (2005) Regulation of azole drug susceptibility by Candida albicans protein kinase CK2. Mol Microbiol 56:559-73
Nobile, Clarissa J; Mitchell, Aaron P (2005) Regulation of cell-surface genes and biofilm formation by the C. albicans transcription factor Bcr1p. Curr Biol 15:1150-5
Richard, Mathias L; Nobile, Clarissa J; Bruno, Vincent M et al. (2005) Candida albicans biofilm-defective mutants. Eukaryot Cell 4:1493-502
Sanchez, Angela A; Johnston, Douglas A; Myers, Carter et al. (2004) Relationship between Candida albicans virulence during experimental hematogenously disseminated infection and endothelial cell damage in vitro. Infect Immun 72:598-601
Li, Mingchun; Martin, Samuel J; Bruno, Vincent M et al. (2004) Candida albicans Rim13p, a protease required for Rim101p processing at acidic and alkaline pHs. Eukaryot Cell 3:741-51
Bruno, Vincent M; Mitchell, Aaron P (2004) Large-scale gene function analysis in Candida albicans. Trends Microbiol 12:157-61
Mitchell, Aaron P (2003) Updated view of Cryptococcus neoformans mating type and virulence. Infect Immun 71:4829-30
Nobile, Clarissa J; Bruno, Vincent M; Richard, Mathias L et al. (2003) Genetic control of chlamydospore formation in Candida albicans. Microbiology 149:3629-37

Showing the most recent 10 out of 11 publications