Candida albicans is among the major human fungal pathogens, causing both mucosal and deep tissue infections. A significant risk factor for invasive C. albicans infection is the presence of an implanted medical device, which provides a surface for biofilm formation. The biofilm creates a protected microenvironment for survival of the pathogen. The immediate goal of studies here proposed is to define the key C. albicans genes and regulatory pathways that govern biofilm formation, and to move forward to yield mechanistic insight. The proposed studies build upon progress in the last funding period that defined two biofilm transcriptional regulators, Bcr1 and Zap1/Csr1, along with several of their functional target genes. Our main objectives now are (1) to define the interactions among Bcr1 regulated gene products that promote biofilm adherence, (2) to determine roles of Zap1 target gene families in accumulation of extracellular matrix material, and (3) to define the functions of newly discovered transcriptional regulators that promote adherence of yeast-form cells

Public Health Relevance

Presence of an implanted medical device, such as a venous catheter, is a major risk factor for lethal disseminated Candida infections. Proposed studies will improve our understanding of mechanisms that permit Candida growth on implanted devices. The mechanistic understanding will permit longer-term development of new therapeutic and diagnostic strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI067703-09
Application #
8604122
Study Section
Special Emphasis Panel (ZRG1-IDM-S (02))
Program Officer
Duncan, Rory A
Project Start
2006-01-01
Project End
2015-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
9
Fiscal Year
2014
Total Cost
$357,730
Indirect Cost
$107,730
Name
Carnegie-Mellon University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Zarnowski, Robert; Westler, William M; Lacmbouh, Ghislain Ade et al. (2014) Novel entries in a fungal biofilm matrix encyclopedia. MBio 5:e01333-14
Desai, Jigar V; Mitchell, Aaron P; Andes, David R (2014) Fungal biofilms, drug resistance, and recurrent infection. Cold Spring Harb Perspect Med 4:
Ganguly, Shantanu; Mitchell, Aaron P (2012) Mini-blaster-mediated targeted gene disruption and marker complementation in Candida albicans. Methods Mol Biol 845:19-39
Finkel, Jonathan S; Xu, Wenjie; Huang, David et al. (2012) Portrait of Candida albicans adherence regulators. PLoS Pathog 8:e1002525
Fanning, Saranna; Xu, Wenjie; Solis, Norma et al. (2012) Divergent targets of Candida albicans biofilm regulator Bcr1 in vitro and in vivo. Eukaryot Cell 11:896-904
Fanning, Saranna; Mitchell, Aaron P (2012) Fungal biofilms. PLoS Pathog 8:e1002585
Ganguly, Shantanu; Bishop, Andrew C; Xu, Wenjie et al. (2011) Zap1 control of cell-cell signaling in Candida albicans biofilms. Eukaryot Cell 10:1448-54
Ganguly, Shantanu; Mitchell, Aaron P (2011) Mucosal biofilms of Candida albicans. Curr Opin Microbiol 14:380-5
Dwivedi, Prabhat; Thompson, Angela; Xie, Zhihong et al. (2011) Role of Bcr1-activated genes Hwp1 and Hyr1 in Candida albicans oral mucosal biofilms and neutrophil evasion. PLoS One 6:e16218
Finkel, J S; Yudanin, N; Nett, J E et al. (2011) Application of the systematic "DAmP" approach to create a partially defective C. albicans mutant. Fungal Genet Biol 48:1056-61

Showing the most recent 10 out of 20 publications