Faculty: William A. Fonzi
Dr. Fonzi is a Professor of Microbiology & Immunology and the Director of M.S. and Ph.D. programs in Microbiology and Immunology within the Department.
- Ph.D., Texas A & M, 1981
- At Georgetown since: 1994
- Contact: (202) 687-1135; email@example.com
Microbial pathogens confront diverse environments within the human host. Rapid adaptation to the physiochemical, nutritional, and other variables within these environments is paramount to the pathogen’s ability to survive and cause disease. Defining the nature of these adaptations and understanding how they contribute to virulence of the pathogen will suggest new targets for intervention and prevention of infections.
Candida albicans, normally a commensal of the gastrointestinal tract, is the most frequent cause of human fungal infections. These range from superficial mucosal lesions to life-threatening blood stream and deep organ infections. C. albicans discerns and adapts to changes in the pH of its environment and this process is intrinsic to its ability to cause infections. Adaptation entails transcriptional changes in a large number of genes, many of which encode cell surface proteins. These include the PHR protein family of glucanosyltransferases that are essential for proper assembly of the cell wall glucans. Defects in these proteins have pleiotropic consequences including, reduced cell wall integrity and defective cell morphology. Since disruption of cell wall assembly is a desirable target of antifungals, the role of these proteins in cell wall assembly is under investigation. Also of interest is another pH-regulated cell surface protein, Pra1p. Pra1p is the major ligand recognized by neutrophils, which provide the initial defense against C. albicans infections. Understanding the regulation and processing of this protein may offer ways to enhance the susceptibility of C. albicans to innate immunity.
- Wangsanut T, Ghosh AK, Metzger PG, Fonzi WA, Rolfes RJ. Grf10 and Bas1 Regulate Transcription of Adenylate and One-Carbon Biosynthesis Genes and Affect Virulence in the Human Fungal Pathogen Candida albicans. mSphere. 2017;2(4).
- Popolo L, Degani G, Camilloni C, Fonzi WA. The PHR Family: The Role of Extracellular Transglycosylases in Shaping Candida albicans Cells. J Fungi (Basel). 2017;3(4).
- Lu S, Mirchevska G, Phatak SS, Li D, Luka J, Calderone RA, et al. Dynamic time warping assessment of high-resolution melt curves provides a robust metric for fungal identification. PLoS One. 2017;12(3):e0173320.
- Degani G, Ragni E, Botias P, Ravasio D, Calderon J, Pianezzola E, et al. Genomic and functional analyses unveil the response to hyphal wall stress in Candida albicans cells lacking beta(1,3)-glucan remodeling. BMC Genomics. 2016;17:482.
- She X, Khamooshi K, Gao Y, Shen Y, Lv Y, Calderone R, et al. Fungal-specific subunits of the Candida albicans mitochondrial complex I drive diverse cell functions including cell wall synthesis. Cell Microbiol. 2015;17(9):1350-64.
- Ghosh AK, Wangsanut T, Fonzi WA, Rolfes RJ. The GRF10 homeobox gene regulates filamentous growth in the human fungal pathogen Candida albicans. FEMS Yeast Res. 2015;15(8).
- Sun N, Li D, Fonzi W, Li X, Zhang L, Calderone R. Multidrug-resistant transporter mdr1p-mediated uptake of a novel antifungal compound. Antimicrob Agents Chemother. 2013;57(12):5931-9.
- Sun N, Fonzi W, Chen H, She X, Zhang L, Calderone R. Azole susceptibility and transcriptome profiling in Candida albicans mitochondrial electron transport chain complex I mutants. Antimicrob Agents Chemother. 2013;57(1):532-42.
- Ragni E, Calderon J, Fascio U, Sipiczki M, Fonzi WA, Popolo L. Phr1p, a glycosylphosphatidylinsitol-anchored beta(1,3)-glucanosyltransferase critical for hyphal wall formation, localizes to the apical growth sites and septa in Candida albicans. Fungal Genet Biol. 2011;48(8):793-805.
- Li D, Chen H, Florentino A, Alex D, Sikorski P, Fonzi WA, et al. Enzymatic Dysfunction of Mitochondrial Complex I of the Candida albicans goa1 Mutant Is Associated with Increased Reactive Oxidants and Cell Death. Eukaryot Cell. 2011;10(5):672-82.