This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Edgerton, M.
Right arrow Articles by Bruenn, J. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Edgerton, M.
Right arrow Articles by Bruenn, J. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, December 2000, p. 3310-3316, Vol. 44, No. 12
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Salivary Histatin 5 and Human Neutrophil Defensin 1 Kill Candida albicans via Shared Pathways

Mira Edgerton,1,2,* Svetlana E. Koshlukova,1 Marcelo W. B. Araujo,1 Rashmi C. Patel,1 Jin Dong,1 and Jeremy A. Bruenn3

Departments of Oral Biology,1 Restorative Dentistry,2 and Biological Sciences,3 State University of New York at Buffalo, Buffalo, New York 14214

Received 24 May 2000/Returned for modification 26 July 2000/Accepted 5 September 2000

Salivary histatins are a family of basic histidine-rich proteins in which therapeutic potential as drugs against oral candidiasis is apparent, considering their potent in vitro antifungal activity and lack of toxicity to humans. Histatin 5 (Hst 5) kills the fungal pathogen Candida albicans via a mechanism that involves binding to specific sites on the yeast cell membrane and subsequent release of cellular ATP in the absence of cytolysis. We explored the killing pathway activated by Hst 5 and compared it to those activated by other antifungal agents. The candidacidal activity of human neutrophil defensin 1 (HNP-1) shared very similar features to Hst 5 cytotoxic action with respect to active concentrations and magnitude of induction of nonlytic ATP efflux, depletion of intracellular ATP pools, and inhibitor profile. Hst 5 and HNP-1 are basic proteins of about 3 kDa; however, they have unique primary sequences and solution structures that cannot explain how these two molecules act so similarly on C. albicans to induce cell death. Our finding that HNP-1 prevented Hst 5 binding to the candidal Hst 5 binding protein suggests that the basis for the overlapping actions of these two naturally occurring antimicrobial proteins may involve interactions with shared yeast components.

* Corresponding author. Mailing address: 310 Foster Hall, SUNY at Buffalo Main Street Campus, 3435 Main St., Buffalo, NY 14214. Phone: (716) 829-3067. Fax: (716) 829-3942. E-mail: edgerto{at}buffalo.edu.

Antimicrobial Agents and Chemotherapy, December 2000, p. 3310-3316, Vol. 44, No. 12
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Conti, H. R., Shen, F., Nayyar, N., Stocum, E., Sun, J. N., Lindemann, M. J., Ho, A. W., Hai, J. H., Yu, J. J., Jung, J. W., Filler, S. G., Masso-Welch, P., Edgerton, M., Gaffen, S. L. (2009). Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. JEM 206: 299-311 [Abstract] [Full Text]  
  • Chaffin, W. L. (2008). Candida albicans Cell Wall Proteins. Microbiol. Mol. Biol. Rev. 72: 495-544 [Abstract] [Full Text]  
  • Beiter, K., Wartha, F., Hurwitz, R., Normark, S., Zychlinsky, A., Henriques-Normark, B. (2008). The Capsule Sensitizes Streptococcus pneumoniae to {alpha}-Defensins Human Neutrophil Proteins 1 to 3. Infect. Immun. 76: 3710-3716 [Abstract] [Full Text]  
  • Gank, K. D., Yeaman, M. R., Kojima, S., Yount, N. Y., Park, H., Edwards, J. E. Jr., Filler, S. G., Fu, Y. (2008). SSD1 Is Integral to Host Defense Peptide Resistance in Candida albicans. Eukaryot Cell 7: 1318-1327 [Abstract] [Full Text]  
  • Wei, G.-X., Campagna, A. N., Bobek, L. A. (2006). Effect of MUC7 peptides on the growth of bacteria and on Streptococcus mutans biofilm. J Antimicrob Chemother 57: 1100-1109 [Abstract] [Full Text]  
  • Vylkova, S., Li, X. S., Berner, J. C., Edgerton, M. (2006). Distinct Antifungal Mechanisms: {beta}-Defensins Require Candida albicans Ssa1 Protein, while Trk1p Mediates Activity of Cysteine-Free Cationic Peptides. Antimicrob. Agents Chemother. 50: 324-331 [Abstract] [Full Text]  
  • Feng, Z., Jiang, B., Chandra, J., Ghannoum, M., Nelson, S., Weinberg, A. (2005). Human Beta-defensins: Differential Activity against Candidal Species and Regulation by Candida albicans. JDR 84: 445-450 [Abstract] [Full Text]  
  • Okamoto, T., Tanida, T., Wei, B., Ueta, E., Yamamoto, T., Osaki, T. (2004). Regulation of Fungal Infection by a Combination of Amphotericin B and Peptide 2, a Lactoferrin Peptide That Activates Neutrophils. CVI 11: 1111-1119 [Abstract] [Full Text]  
  • Bowdish, D. M. E., Davidson, D. J., Speert, D. P., Hancock, R. E. W. (2004). The Human Cationic Peptide LL-37 Induces Activation of the Extracellular Signal-Regulated Kinase and p38 Kinase Pathways in Primary Human Monocytes. J. Immunol. 172: 3758-3765 [Abstract] [Full Text]  
  • Joly, S., Maze, C., McCray, P. B. Jr., Guthmiller, J. M. (2004). Human {beta}-Defensins 2 and 3 Demonstrate Strain-Selective Activity against Oral Microorganisms. J. Clin. Microbiol. 42: 1024-1029 [Abstract] [Full Text]  
  • Li, X. S., Reddy, M. S., Baev, D., Edgerton, M. (2003). Candida albicans Ssa1/2p Is the Cell Envelope Binding Protein for Human Salivary Histatin 5. J. Biol. Chem. 278: 28553-28561 [Abstract] [Full Text]  
  • Bobek, L. A., Situ, H. (2003). MUC7 20-Mer: Investigation of Antimicrobial Activity, Secondary Structure, and Possible Mechanism of Antifungal Action. Antimicrob. Agents Chemother. 47: 643-652 [Abstract] [Full Text]  
  • Lupetti, A., Paulusma-Annema, A., Senesi, S., Campa, M., van Dissel, J. T., Nibbering, P. H. (2002). Internal Thiols and Reactive Oxygen Species in Candidacidal Activity Exerted by an N-Terminal Peptide of Human Lactoferrin. Antimicrob. Agents Chemother. 46: 1634-1639 [Abstract] [Full Text]  
  • Edgerton, M., Koshlukova, S.E. (2000). Salivary Histatin 5 and its Similarities to the Other Antimicrobial Proteins in Human Saliva. ADR 14: 16-21 [Abstract]  
  • Helmerhorst, E. J., Troxler, R. F., Oppenheim, F. G. (2001). The human salivary peptide histatin 5 exerts its antifungal activity through the formation of reactive oxygen species. Proc. Natl. Acad. Sci. USA 98: 14637-14642 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»