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. 1996 Apr;64(4):1240–1245. doi: 10.1128/iai.64.4.1240-1245.1996

Susceptibility of Neisseria gonorrhoeae to protegrins.

X D Qu 1, S S Harwig 1, A M Oren 1, W M Shafer 1, R I Lehrer 1
PMCID: PMC173910  PMID: 8606085

Abstract

We developed a sensitive and quantitative radial diffusion method to ascertain the susceptibility of six strains of Neisseria gonorrhoeae to antimicrobial peptides derived from mammalian leukocytes. The test organisms included the well-characterized serum-resistant FA19 and serum-sensitive F62 strains plus four antibiotic-resistant clinical isolates. Although each N. gonorrhoeae strain was resistant to human neutrophil defensins, all six were exquisitely sensitive to protegrins, a family of small beta-sheet antimicrobial peptides recently identified in porcine leukocytes. Protegrin-treated N. gonorrhoeae became vacuolated and had striking membrane changes when viewed by transmission and scanning electron microscopy. Because low concentrations of protegrins can also inactivate Chlamydia trachomatis and human immunodeficiency virus, they show promise for development as topical agents to avert sexually transmitted diseases.

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Selected References

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  1. Cannon J. G., Lee T. J., Guymon L. F., Sparling P. F. Genetics of serum resistance in Neisseria gonorrhoeae: the sac-1 genetic locus. Infect Immun. 1981 May;32(2):547–552. doi: 10.1128/iai.32.2.547-552.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Casey S. G., Shafer W. M., Spitznagel J. K. Anaerobiosis increases resistance of Neisseria gonorrhoeae to O2-independent antimicrobial proteins from human polymorphonuclear granulocytes. Infect Immun. 1985 Feb;47(2):401–407. doi: 10.1128/iai.47.2.401-407.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Casey S. G., Shafer W. M., Spitznagel J. K. Neisseria gonorrhoeae survive intraleukocytic oxygen-independent antimicrobial capacities of anaerobic and aerobic granulocytes in the presence of pyocin lethal for extracellular gonococci. Infect Immun. 1986 May;52(2):384–389. doi: 10.1128/iai.52.2.384-389.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Harwig S. S., Ganz T., Lehrer R. I. Neutrophil defensins: purification, characterization, and antimicrobial testing. Methods Enzymol. 1994;236:160–172. doi: 10.1016/0076-6879(94)36015-4. [DOI] [PubMed] [Google Scholar]
  5. Harwig S. S., Swiderek K. M., Lee T. D., Lehrer R. I. Determination of disulphide bridges in PG-2, an antimicrobial peptide from porcine leukocytes. J Pept Sci. 1995 May-Jun;1(3):207–215. doi: 10.1002/psc.310010308. [DOI] [PubMed] [Google Scholar]
  6. Iwanaga S., Muta T., Shigenaga T., Seki N., Kawano K., Katsu T., Kawabata S. Structure-function relationships of tachyplesins and their analogues. Ciba Found Symp. 1994;186:160–175. doi: 10.1002/9780470514658.ch10. [DOI] [PubMed] [Google Scholar]
  7. Kokryakov V. N., Harwig S. S., Panyutich E. A., Shevchenko A. A., Aleshina G. M., Shamova O. V., Korneva H. A., Lehrer R. I. Protegrins: leukocyte antimicrobial peptides that combine features of corticostatic defensins and tachyplesins. FEBS Lett. 1993 Jul 26;327(2):231–236. doi: 10.1016/0014-5793(93)80175-t. [DOI] [PubMed] [Google Scholar]
  8. Lehrer R. I., Rosenman M., Harwig S. S., Jackson R., Eisenhauer P. Ultrasensitive assays for endogenous antimicrobial polypeptides. J Immunol Methods. 1991 Mar 21;137(2):167–173. doi: 10.1016/0022-1759(91)90021-7. [DOI] [PubMed] [Google Scholar]
  9. Rest R. F., Fischer S. H., Ingham Z. Z., Jones J. F. Interactions of Neisseria gonorrhoeae with human neutrophils: effects of serum and gonococcal opacity on phagocyte killing and chemiluminescence. Infect Immun. 1982 May;36(2):737–744. doi: 10.1128/iai.36.2.737-744.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Rowe P. M. Research into topical microbicides against STDs. Lancet. 1995 May 13;345(8959):1231–1231. doi: 10.1016/s0140-6736(95)92008-0. [DOI] [PubMed] [Google Scholar]
  11. Selsted M. E., Szklarek D., Lehrer R. I. Purification and antibacterial activity of antimicrobial peptides of rabbit granulocytes. Infect Immun. 1984 Jul;45(1):150–154. doi: 10.1128/iai.45.1.150-154.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Shafer W. M., Onunka V. C., Martin L. E. Antigonococcal activity of human neutrophil cathepsin G. Infect Immun. 1986 Oct;54(1):184–188. doi: 10.1128/iai.54.1.184-188.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Shafer W. M., Rest R. F. Interactions of gonococci with phagocytic cells. Annu Rev Microbiol. 1989;43:121–145. doi: 10.1146/annurev.mi.43.100189.001005. [DOI] [PubMed] [Google Scholar]
  14. Shafer W. M., Shepherd M. E., Boltin B., Wells L., Pohl J. Synthetic peptides of human lysosomal cathepsin G with potent antipseudomonal activity. Infect Immun. 1993 May;61(5):1900–1908. doi: 10.1128/iai.61.5.1900-1908.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Tamamura H., Murakami T., Horiuchi S., Sugihara K., Otaka A., Takada W., Ibuka T., Waki M., Yamamoto N., Fujii N. Synthesis of protegrin-related peptides and their antibacterial and anti-human immunodeficiency virus activity. Chem Pharm Bull (Tokyo) 1995 May;43(5):853–858. doi: 10.1248/cpb.43.853. [DOI] [PubMed] [Google Scholar]
  16. Yasin B., Harwig S. S., Lehrer R. I., Wagar E. A. Susceptibility of Chlamydia trachomatis to protegrins and defensins. Infect Immun. 1996 Mar;64(3):709–713. doi: 10.1128/iai.64.3.709-713.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Zhao C., Ganz T., Lehrer R. I. The structure of porcine protegrin genes. FEBS Lett. 1995 Jul 17;368(2):197–202. doi: 10.1016/0014-5793(95)00633-k. [DOI] [PubMed] [Google Scholar]
  18. Zhao C., Liu L., Lehrer R. I. Identification of a new member of the protegrin family by cDNA cloning. FEBS Lett. 1994 Jun 13;346(2-3):285–288. doi: 10.1016/0014-5793(94)00493-5. [DOI] [PubMed] [Google Scholar]

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