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.
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.
|Herwald, Sanna E; Zucchi, Paola C; Tan, Shumin et al. (2017) The two transmembrane regions of Candida albicans Dfi1 contribute to its biogenesis. Biochem Biophys Res Commun 488:153-158|
|Regan, Hannah; Scaduto, Christine M; Hirakawa, Matthew P et al. (2017) Negative regulation of filamentous growth in Candida albicans by Dig1p. Mol Microbiol 105:810-824|
|Gunsalus, Kearney T W; Tornberg-Belanger, Stephanie N; Matthan, Nirupa R et al. (2016) Manipulation of Host Diet To Reduce Gastrointestinal Colonization by the Opportunistic Pathogen Candida albicans. mSphere 1:|
|Gunsalus, Kearney T W; Kumamoto, Carol A (2016) Transcriptional Profiling of Candida albicans in the Host. Methods Mol Biol 1356:17-29|
|Tyc, Katarzyna M; Herwald, Sanna E; Hogan, Jennifer A et al. (2016) The game theory of Candida albicans colonization dynamics reveals host status-responsive gene expression. BMC Syst Biol 10:20|
|Tebbji, Faiza; Chen, Yaolin; Richard Albert, Julien et al. (2014) A functional portrait of Med7 and the mediator complex in Candida albicans. PLoS Genet 10:e1004770|
|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|
|Davis, Talya R; Zucchi, Paola C; Kumamoto, Carol A (2013) Calmodulin binding to Dfi1p promotes invasiveness of Candida albicans. PLoS One 8:e76239|
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