This research project investigates the mechanisms used by the opportunistic fungal pathogen, Candida albicans to produce disease. The long term goal of this research is to understand how C. albicans cells cause infection. Environmental sensing is likely to be important for regulation of activities that promote virulence, such as the ability of C. albicans cells to convert into invasive filamentous hyphae, which penetrate into host tissue. Studies of invasiveness under laboratory conditions have shown that C. albicans cells sense contact with a semi-solid matrix, causing them to produce invasive hyphae. A plasma membrane protein that is needed for invasive growth in response to contact with agar medium and may be a sensor of contact has been characterized. To evaluate the importance of contact sensing for invasion during infection, a mutant lacking the sensor will be studied in several animal models of infection (Aim 1). Preliminary studies suggest that other plasma membrane proteins also participate in contact sensing.
Aim 2 will focus on analyzing double or triple mutants lacking several components that are important for invasiveness in animal models of infection.
In Aim 3, signaling pathways that are activated by the plasma membrane proteins of interest will be investigated. To understand how the contact sensing process takes place, Aim 4 will seek to identify and characterize proteins that function with the contact sensing protein. These studies will increase the understanding of regulatory mechanisms that are important in C. albicans pathogenesis.

Public Health Relevance

Candida albicans is an important pathogen of hospitalized or otherwise immunocompromised patients. Infection by C. albicans is characterized by growth of the organism into the tissues of its host. This research project seeks to understand Candida activities that are necessary for the growth of the organism into host tissue so that future therapies aimed at blocking growth into tissue might be developed.

National Institute of Health (NIH)
Research Project (R01)
Project #
Application #
Study Section
Pathogenic Eukaryotes Study Section (PTHE)
Program Officer
Duncan, Rory A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Tufts University
Schools of Medicine
United States
Zip Code
Herwald, Sanna E; Kumamoto, Carol A (2014) Candida albicans Niche Specialization: Features That Distinguish Biofilm Cells from Commensal Cells. Curr Fungal Infect Rep 8:179-184
Delattin, Nicolas; De Brucker, Katrijn; Craik, David J et al. (2014) Structure-activity relationship study of the plant-derived decapeptide OSIP108 inhibiting Candida albicans biofilm formation. Antimicrob Agents Chemother 58:4974-7
Pierce, Jessica V; Dignard, Daniel; Whiteway, Malcolm et al. (2013) Normal adaptation of Candida albicans to the murine gastrointestinal tract requires Efg1p-dependent regulation of metabolic and host defense genes. Eukaryot Cell 12:37-49
Perez, J Christian; Kumamoto, Carol A; Johnson, Alexander D (2013) Candida albicans commensalism and pathogenicity are intertwined traits directed by a tightly knit transcriptional regulatory circuit. PLoS Biol 11:e1001510
Thevissen, Karin; de Mello Tavares, Patricia; Xu, Deming et al. (2012) The plant defensin RsAFP2 induces cell wall stress, septin mislocalization and accumulation of ceramides in Candida albicans. Mol Microbiol 84:166-80
Kumamoto, Carol A (2011) Inflammation and gastrointestinal Candida colonization. Curr Opin Microbiol 14:386-91
Kumamoto, Carol A; Pierce, Jessica V (2011) Immunosensing during colonization by Candida albicans: does it take a village to colonize the intestine? Trends Microbiol 19:263-7