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, and 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 long-term goal s to understand how the individual target genes of the circuit contribute to the key properties of biofilms, how mixed biofilm are formed between C. albicans and certain bacterial species, and how the biofilm transcription network differs among pathogenic species closely related to C. albicans.

Public Health Relevance

C. albicans is the most prevalent fungal pathogen of humans, causing 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; therefore, understanding biofilms in detail may lead to improvements in preventing and treating C. albicans infections.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
5R01AI083311-07
Application #
9187403
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Duncan, Rory A
Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2017
Total Cost
Indirect Cost
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
94118
Winter, Michael B; Salcedo, Eugenia C; Lohse, Matthew B et al. (2016) Global Identification of Biofilm-Specific Proteolysis in Candida albicans. MBio 7:
Wells, Melissa L; Washington, Onica L; Hicks, Stephanie N et al. (2015) Post-transcriptional regulation of transcript abundance by a conserved member of the tristetraprolin family in Candida albicans. Mol Microbiol 95:1036-53
Nobile, Clarissa J; Johnson, Alexander D (2015) Candida albicans Biofilms and Human Disease. Annu Rev Microbiol 69:71-92
Fox, Emily P; Bui, Catherine K; Nett, Jeniel E et al. (2015) An expanded regulatory network temporally controls Candida albicans biofilm formation. Mol Microbiol 96:1226-39
Mancera, Eugenio; Porman, Allison M; Cuomo, Christina A et al. (2015) Finding a Missing Gene: EFG1 Regulates Morphogenesis in Candida tropicalis. G3 (Bethesda) 5:849-56
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
Kavanaugh, Nicole L; Zhang, Angela Q; Nobile, Clarissa J et al. (2014) Mucins suppress virulence traits of Candida albicans. MBio 5:e01911
Lin, Ching-Hsuan; Kabrawala, Shail; Fox, Emily P et al. (2013) Genetic control of conventional and pheromone-stimulated biofilm formation in Candida albicans. PLoS Pathog 9:e1003305
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

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