HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Baev, D. Articles by Edgerton, M. Search for Related Content PubMed PubMed Citation Articles by Baev, D. Articles by Edgerton, M. Agricola Articles by Baev, D. Articles by Edgerton, M.

Genetically engineered human salivary histatin genes are functional in Candida albicans: development of a new system for studying histatin candidacidal activity

Departments of Oral Biology¹ and Restorative Dentistry², School of Dental Medicine, State University of New York at Buffalo Main Street Campus, 3435 Main Street, Buffalo, NY 14214, USA

Author for correspondence: Mira Edgerton. Tel: +1 716 829 3067. Fax: +1 716 829 3942. e-mail: edgerto{at}buffalo.edu

Histatins are a structurally related family of salivary proteins known as histidine-rich proteins that are produced and secreted by the human major salivary glands. In vitro, histatins are potent cytotoxic proteins with selectivity for pathogenic yeasts including Candida albicans. Studies that investigate the mechanism of action of histatin proteins upon this important human pathogen have used a candidacidal assay in which the histatin is applied extracellularly. In order to develop a model system to study the mechanism of histatin action independently from binding and translocation events, the authors constructed C. albicans strains that contain chromosomally encoded human salivary histatin genes under the control of a regulated promoter. Intracellular expression of either histatin 5 or histatin 3 induced cell killing and ATP release in parallel. Since histatin killing can be initiated solely from intracellular sites, extracellular binding and internalization are preceding transport events. Thus the mechanism of histatin-induced ATP release does not require extracellular binding, and intracellular targets alone can activate ATP release. By employing a codon-optimization strategy it was shown that expression of heterologous sequences in C. albicans can be a useful tool for functional studies.

Keywords: histidine-rich proteins, statherin, codon-optimization, RT-PCR

Abbreviations: 3'UTR, 3' untranslated region; 5-FOA, 5-fluoroorotic acid; LD-PCR, long-distance PCR; wt, wild-type

This article has been cited by other articles:

				W. L. Chaffin Candida albicans Cell Wall Proteins Microbiol. Mol. Biol. Rev., September 1, 2008; 72(3): 495 - 544. [Abstract] [Full Text] [PDF]

				J. Zhu, P. W. Luther, Q. Leng, and A. J. Mixson Synthetic histidine-rich peptides inhibit Candida species and other fungi in vitro: role of endocytosis and treatment implications. Antimicrob. Agents Chemother., August 1, 2006; 50(8): 2797 - 2805. [Abstract] [Full Text] [PDF]

				D. Baev, A. Rivetta, S. Vylkova, J. N. Sun, G.-F. Zeng, C. L. Slayman, and M. Edgerton The TRK1 Potassium Transporter Is the Critical Effector for Killing of Candida albicans by the Cationic Protein, Histatin 5 J. Biol. Chem., December 31, 2004; 279(53): 55060 - 55072. [Abstract] [Full Text] [PDF]

				D. Wunder, J. Dong, D. Baev, and M. Edgerton Human Salivary Histatin 5 Fungicidal Action Does Not Induce Programmed Cell Death Pathways in Candida albicans Antimicrob. Agents Chemother., January 1, 2004; 48(1): 110 - 115. [Abstract] [Full Text] [PDF]

				J. Dong, S. Vylkova, X.S. Li, and M. Edgerton Calcium Blocks Fungicidal Activity of Human Salivary Histatin 5 through Disruption of Binding with Candida albicans J. Dent. Res., September 1, 2003; 82(9): 748 - 752. [Abstract] [Full Text] [PDF]

				X. S. Li, M. S. Reddy, D. Baev, and M. Edgerton Candida albicans Ssa1/2p Is the Cell Envelope Binding Protein for Human Salivary Histatin 5 J. Biol. Chem., August 1, 2003; 278(31): 28553 - 28561. [Abstract] [Full Text] [PDF]

				D. Baev, A. Rivetta, X. S. Li, S. Vylkova, E. Bashi, C. L. Slayman, and M. Edgerton Killing of Candida albicans by Human Salivary Histatin 5 Is Modulated, but Not Determined, by the Potassium Channel TOK1 Infect. Immun., June 1, 2003; 71(6): 3251 - 3260. [Abstract] [Full Text] [PDF]

				D. Baev, X. S. Li, J. Dong, P. Keng, and M. Edgerton Human Salivary Histatin 5 Causes Disordered Volume Regulation and Cell Cycle Arrest in Candida albicans Infect. Immun., September 1, 2002; 70(9): 4777 - 4784. [Abstract] [Full Text] [PDF]