The yeast Candida albicans is a normal resident of the human digestive tract. It is also the most common fungal pathogen of humans, causing both mucosal and systemic infections, particularly in immune compromised patients. This proposal seeks to understand how C. albicans orchestrates the formation of biofilms - resilient, surface- associated, organized groups of cells. Biofilm formation is medically relevant because new C. albicans infections are highly correlated with implanted medical devices, which provide efficient substrates for biofilm formation. Our approach to the study of biofilm formation is through dissection of the transcriptional circuitry that controls this process. Our overarching goal is to understand how the individual target genes of the circuit contribute to the key properties of biofilms, such as drug resistance, cell-cell adhesion, and production of extracellular matrix.

Public Health Relevance

C. albicans is the most prevalent fungal pathogen of humans. It causes superficial infections in normal humans and life threatening, systemic infections in immune compromised individuals. This proposal seeks to understand how C. albicans forms biofilms, communities of cells particularly resistant to mechanical force and antifungal drugs. C. albicans biofilms formed on implanted medical devices and are a major source of new infections. Understanding biofilms in more detail may lead to improvements in preventing and treating C. albicans infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI083311-04
Application #
8586244
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Duncan, Rory A
Project Start
2010-12-01
Project End
2015-11-30
Budget Start
2013-12-01
Budget End
2014-11-30
Support Year
4
Fiscal Year
2014
Total Cost
$330,349
Indirect Cost
$105,349
Name
University of California San Francisco
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Kavanaugh, Nicole L; Zhang, Angela Q; Nobile, Clarissa J et al. (2014) Mucins suppress virulence traits of Candida albicans. MBio 5:e01911
Nobile, Clarissa J; Fox, Emily P; Hartooni, Nairi et al. (2014) A histone deacetylase complex mediates biofilm dispersal and drug resistance in Candida albicans. MBio 5:e01201-14
Fox, Emily P; Cowley, Elise S; Nobile, Clarissa J et al. (2014) Anaerobic bacteria grow within Candida albicans biofilms and induce biofilm formation in suspension cultures. Curr Biol 24:2411-6
Nobile, Clarissa J; Fox, Emily P; Nett, Jeniel E et al. (2012) A recently evolved transcriptional network controls biofilm development in Candida albicans. Cell 148:126-38