This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Qu, X. D. Articles by Lehrer, R. I. Search for Related Content PubMed PubMed Citation Articles by Qu, X. D. Articles by Lehrer, R. I.

 Previous Article  |  Next Article 

Infect. Immun., Feb 1997, 636-639, Vol 65, No. 2
Copyright © 1997, American Society for Microbiology

Protegrin structure and activity against Neisseria gonorrhoeae

XD Qu, SS Harwig, WM Shafer and RI Lehrer
Department of Medicine, UCLA Center for the Health Sciences, Los Angeles, California 90095-1690, USA.

Protegrin 1 (PG-1) is a broad-spectrum antimicrobial peptide that contains 18 amino acid residues (RG GRLCYCRRRFCVCVGR) and has two intramolecular cystine disulfide bonds. To determine the minimal structure responsible for protegrin-mediated activity against Neisseria gonorrhoeae, we synthesized 15 protegrin variants and tested them against two well-characterized gonococcal strains. The MICs of PG-1 were 0.61 microM (1.31 microg/ml) for the serum-sensitive strain F 62 and 0.98 microM (2.11 microg/ml) for the serum-resistant strain FA 19. Six amino acid residues (Arg1, Gly2, Gly3, Arg4, Gly17, and Arg18) and either disulfide bond could be deleted from PG-1 without impairing its potency against strain F 62. In contrast, only Gly17 and Arg18 could be removed without decreasing its activity against FA 19. Protegrin congener 64a (PC-64a; LTYCRRRFCVTV), a variant of PG-1 with 12 amino acid residues and one disulfide bond, displayed MICs of 0.45 microM (0.68 microg/ml) for strain F 62 and 1.37 microM (2.07 microg/ml) for strain FA 19, which approximated those of intact PG-1. Serum-sensitive sac-1+ and sac-3+ transformants of N. gonorrhoeae FA 19 and two FA 19 derivatives with truncated lipooligosaccharide structures were more susceptible to PG-1 and variants with altered disulfide structures. These data suggest that structurally simpler protegrin variants, such as PC-64a, could be used as topical microbicides for N. gonorrhoeae. They also suggest that the cystine-stabilized antiparallel beta-sheet formed by PG-1 residues 5 to 16 is principally responsible for its activity against gonococci.

This article has been cited by other articles:

• Cheung, Q. C. K., Turner, P. V., Song, C., Wu, D., Cai, H. Y., MacInnes, J. I., Li, J. (2008). Enhanced Resistance to Bacterial Infection in Protegrin-1 Transgenic Mice. Antimicrob. Agents Chemother. 52: 1812-1819 [Abstract] [Full Text]  
• Klotman, M. E., Rapista, A., Teleshova, N., Micsenyi, A., Jarvis, G. A., Lu, W., Porter, E., Chang, T. L. (2008). Neisseria gonorrhoeae-Induced Human Defensins 5 and 6 Increase HIV Infectivity: Role in Enhanced Transmission. J. Immunol. 180: 6176-6185 [Abstract] [Full Text]  
• Liao, M., Ruddock, P. S., Rizvi, A. S., Hall, S. H., French, F. S., Dillon, J. R. (2005). Cationic peptide of the male reproductive tract, HE2{alpha}, displays antimicrobial activity against Neisseria gonorrhoeae, Staphylococcus aureus and Enterococcus faecalis. J Antimicrob Chemother 56: 957-961 [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]  
• Hong, S. Y., Oh, J. E., Lee, K. H. (1999). In Vitro Antifungal Activity and Cytotoxicity of a Novel Membrane-Active Peptide. Antimicrob. Agents Chemother. 43: 1704-1707 [Abstract] [Full Text]  
• Wu, M., Hancock, R. E. W. (1999). Interaction of the Cyclic Antimicrobial Cationic Peptide Bactenecin with the Outer and Cytoplasmic Membrane. J. Biol. Chem. 274: 29-35 [Abstract] [Full Text]  
• Hong, S. Y., Oh, J. E., Kwon, M. y., Choi, M. J., Lee, J. H., Lee, B. L., Moon, H. M., Lee, K. H. (1998). Identification and Characterization of Novel Antimicrobial Decapeptides Generated by Combinatorial Chemistry. Antimicrob. Agents Chemother. 42: 2534-2541 [Abstract] [Full Text]  
• Fortney, K., Totten, P. A., Lehrer, R. I., Spinola, S. M. (1998). Haemophilus ducreyi Is Susceptible to Protegrin. Antimicrob. Agents Chemother. 42: 2690-2693 [Abstract] [Full Text]  
• Cho, Y., Turner, J. S., Dinh, N.-N., Lehrer, R. I. (1998). Activity of Protegrins against Yeast-Phase Candida albicans. Infect. Immun. 66: 2486-2493 [Abstract] [Full Text]  
• Shafer, W. M., Qu, X.-D., Waring, A. J., Lehrer, R. I. (1998). Modulation of Neisseria gonorrhoeae susceptibility to vertebrate antibacterial peptides due to a member of the resistance/nodulation/division efflux pump family. Proc. Natl. Acad. Sci. USA 95: 1829-1833 [Abstract] [Full Text]