Dr. Fonzi is a Professor of Microbiology & Immunology and Director of Graduate Programs at 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.
- Liao WL, Ramón AM, Fonzi WA. GLN3 encodes a global regulator of nitrogen metabolism and virulence of C. albicans. Fungal Genet Biol. 2008 Apr;45(4):514-26. Epub 2007 Sep 7.
- Soloviev DA, Fonzi WA, Sentandreu R, Pluskota E, Forsyth CB, Yadav S, Plow EF. Identification of pH-regulated antigen 1 released from Candida albicans as the major ligand for leukocyte integrin alphaMbeta2. J Immunol. 2007 Feb 15;178(4):2038-46.
- Sharkey LL, Liao WL, Ghosh AK, Fonzi WA. Flanking direct repeats of hisG alter URA3 marker expression at the HWP1 locus of Candida albicans. Microbiology. 2005 Apr;151(Pt 4):1061-71.
- de la Rosa JM, Ruiz T, Fonzi WA, Rodríguez L. Analysis of heterologous expression of Candida albicans SEC61 gene reveals differences in Sec61p homologues related to species-specific functionality. Fungal Genet Biol. 2004 Oct;41(10):941-53.
- Limjindaporn T, Khalaf RA, Fonzi WA. Nitrogen metabolism and virulence of Candida albicans require the GATA-type transcriptional activator encoded by GAT1. Mol Microbiol. 2003 Nov;50(3):993-1004.
- Ramón AM, Fonzi WA. Diverged binding specificity of Rim101p, the Candida albicans ortholog of PacC. Eukaryot Cell. 2003 Aug;2(4):718-28.
- Fonzi WA. Role of pH response in Candida albicans virulence. Mycoses. 2002;45 Suppl 1:16-21.
- McNemar MD, Fonzi WA. Conserved serine/threonine kinase encoded by CBK1 regulates expression of several hypha-associated transcripts and genes encoding cell wall proteins in Candida albicans. J Bacteriol. 2002 Apr;184(7):2058-61.
- Porta A, Wang Z, Ramon A, Mühlschlegel FA, Fonzi WA. Spontaneous second-site suppressors of the filamentation defect of prr1Delta mutants define a critical domain of Rim101p in Candida albicans. Mol Genet Genomics. 2001 Dec;266(4):624-31. Epub 2001 Oct 11.
- Calderone RA, Fonzi WA. Virulence factors of Candida albicans. Trends Microbiol. 2001 Jul;9(7):327-35. Review.