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 Cho, Y.
Right arrow Articles by Lehrer, R. I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cho, Y.
Right arrow Articles by Lehrer, R. I.

 Previous Article  |  Next Article 

Infect Immun, June 1998, p. 2486-2493, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Activity of Protegrins against Yeast-Phase Candida albicans

Yoon Cho,1 Jeffrey S. Turner,1 Nhu-Nguyen Dinh,1 and Robert I. Lehrer1,2,*

Department of Medicine1 and Molecular Biology Institute,2 UCLA School of Medicine, Los Angeles, California

Received 17 December 1997/Returned for modification 29 January 1998/Accepted 5 March 1998

We used a two-stage radial diffusion assay to perform a structure-activity study of the antifungal effects of protegrin-1 (PG-1) on yeast-phase Candida albicans. While doing so, we computed MICs from the radial diffusion assay data by three methods and compared the respective values with results from colony count and broth microdilution assays. This allowed us to identify several technical modifications that improved the sensitivity and accuracy of radial diffusion assays. We found that both PG-1 and enantiomeric PG-1 (composed exclusively of D-amino acids) were potently fungicidal for yeast-phase C. albicans. The protegrins PG-2, -3, and -5, but not PG-4, were as effective as PG-1. At least one intramolecular disulfide bond was required to retain optimal candidacidal activity at physiological NaCl concentrations. Truncated variants of PG-1 that lacked its first four residues showed decreased candidacidal activity, although their activity against bacteria was substantially intact. Altering the beta -turn region (residues 9 to 12) of PG-1 or its variants further decreased candidacidal activity. These studies suggest that only 12 residues are needed to endow protegrin molecules with strong antibacterial activity and that at least 4 additional residues are needed to add potent antifungal properties. Thus, the 16-residue protegrin PG-2 likely represents the minimal structure needed for broad-spectrum antimicrobial activity encompassing bacteria and fungi.

* Corresponding author. Mailing address: Department of Medicine, Box 951690, 10833 LeConte Ave., Los Angeles, CA 90095-1690. Phone: (310) 825-5340. Fax: (310) 206-8766. E-mail: rlehrer{at}med1.medsch.ucla.edu.

Infect Immun, June 1998, p. 2486-2493, Vol. 66, No. 6
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Wei, G., de Leeuw, E., Pazgier, M., Yuan, W., Zou, G., Wang, J., Ericksen, B., Lu, W.-Y., Lehrer, R. I., Lu, W. (2009). Through the Looking Glass, Mechanistic Insights from Enantiomeric Human Defensins. J. Biol. Chem. 284: 29180-29192 [Abstract] [Full Text]  
  • Ghiselli, R., Giacometti, A., Cirioni, O., Mocchegiani, F., Silvestri, C., Orlando, F., Kamysz, W., Licci, A., Nadolski, P., Della Vittoria, A., Lukasiak, J., Scalise, G., Saba, V. (2007). Pretreatment With the Protegrin IB-367 Affects Gram-Positive Biofilm and Enhances the Therapeutic Efficacy of Linezolid in Animal Models of Central Venous Catheter Infection. JPEN J Parenter Enteral Nutr 31: 463-468 [Abstract] [Full Text]  
  • Benincasa, M., Scocchi, M., Pacor, S., Tossi, A., Nobili, D., Basaglia, G., Busetti, M., Gennaro, R. (2006). Fungicidal activity of five cathelicidin peptides against clinically isolated yeasts. J Antimicrob Chemother 58: 950-959 [Abstract] [Full Text]  
  • Jenssen, H., Hamill, P., Hancock, R. E. W. (2006). Peptide Antimicrobial Agents. Clin. Microbiol. Rev. 19: 491-511 [Abstract] [Full Text]  
  • Deslouches, B., Islam, K., Craigo, J. K., Paranjape, S. M., Montelaro, R. C., Mietzner, T. A. (2005). Activity of the De Novo Engineered Antimicrobial Peptide WLBU2 against Pseudomonas aeruginosa in Human Serum and Whole Blood: Implications for Systemic Applications. Antimicrob. Agents Chemother. 49: 3208-3216 [Abstract] [Full Text]  
  • Giacometti, A, Cirioni, O, Ghiselli, R, Mocchegiani, F, D'Amato, G, Del Prete, M S., Orlando, F, Kamysz, W, Lukasiak, J, Saba, V, Scalise, G (2003). Administration of protegrin peptide IB-367 to prevent endotoxin induced mortality in bile duct ligated rats. Gut 52: 874-878 [Abstract] [Full Text]  
  • Gidalevitz, D., Ishitsuka, Y., Muresan, A. S., Konovalov, O., Waring, A. J., Lehrer, R. I., Lee, K. Y. C. (2003). Interaction of antimicrobial peptide protegrin with biomembranes. Proc. Natl. Acad. Sci. USA 100: 6302-6307 [Abstract] [Full Text]  
  • Steinstraesser, L., Tack, B. F., Waring, A. J., Hong, T., Boo, L. M., Fan, M.-H., Remick, D. I., Su, G. L., Lehrer, R. I., Wang, S. C. (2002). Activity of Novispirin G10 against Pseudomonas aeruginosa In Vitro and in Infected Burns. Antimicrob. Agents Chemother. 46: 1837-1844 [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»