Antifungal activities of peptides with the sequence 10-17 of magainin 2 at the N-termini against aspergillus fumigatus

Antifungal Activities of Peptides with the Sequence 10-17 of Magainin 2 at the N-termini against Aspergillus fumigatus

  • Published : 1996.09.01

Abstract

Two peptides, MA-inv AND MA-ME, with the sequence 10-17 of maganin 2 at their-N-termini were designed and synthesized. The peptides had higher antifungal activities against Aspergilus fumigatus without hemolytic activities. The minimal inhibition concentratory (MIC) values of both peptides against A. fumigatus were 5 .mu.g/ml, whereas those of the native peptides, magainin 2 and melittin, were 10.mu.g/ml. At 3 .mu.g/ml, MA-inv and MA-ME inhibited the mycelium growth of A. fumigatus by 94.6% and 97.3% respectively, whereas magainin 2 and melittin inhibited by 62.2% and 32.4, respectively. MA-inv showed up to 80% inhibition of (1, 3)-.betha.-D-glucan synthase activity of A. fumigatus. The peptides also showed up to 80% inhibition of (1, 3)-.betha.-D glucan synthase activity of A. fumigatus. The peptides also showed antifungal activities for other fungi of Aspergillus sp. However, the antibiotic activities of MA-ME against Escherichia coli, Bacillus subtilis and Fusarium oxysporum were more effective than those of MA-inv, suggesting that the C-terminal sequences of MA-inv and MA-ME may also influence their antibiotic activities. These results suggest that the N-terminal sequence of the designed peptides, KKFGKAFV, is important for their antifungal activities against A. fumigatus and their C- terminal sequences are related to the organism selectivity.

References

  1. CRC Crit. Rev. Clin. Lab. Sci. v.13 The clinical spectrum of aspergillosis-part2: Classification and description of saprophytic, allergic, and invasive variants of human disease E.J. Bardana Jr.
  2. J. Allergy Clin. Immunol. v.81 A pathologic study of allergic bronchopulmonary aspergillosis Slavin, R.G.;Bedrossian, C.W.;Hutcheson, P.S.;Pittman, S.;Salinnas-Madrigal, L.;Tsai, C.C.;G.J. Gleich
  3. Applied and Environ. Microbiol. v.53 Tremorgenic mycotoxins from Aspergillus fumigatus as a possible occupation health problem in sawmills Land C.J.;Hult, K.;Fuchs, R.;Hagelberg, S.;H. Lundstr
  4. Proc. Natl. Acad. Sci. USA v.84 Magainins, a class of antimicrobial peptides from Xenopus skin : isolation, characterization of two active forms, and partial cDNA sequence of a precursor Zasloff, M.
  5. Proc. Natl. Acad. Sci. USA v.88 Antibiotic magainins exert cytolytic activity against transformed cell lines through channel formation Cruciani, R.A.;Barker, J.L.;Zasloff, M.;Chen. H.-C.;O. Colamonici
  6. Science v.177 Bee and wasp venoms Habermann, E.
  7. Nature v.292 Sequence and specificity of two antibacterial proteins involved in insect immunity Stainer, H.;Hultmark, D.;Engstrom, A.;Bennich, H.;H.G. Boman
  8. FEBS Lett. v.236 Synthetic Magainin analogues with improved antimicrobial activity Chen, H.-C.;Brown, J.H.;Morell, J.L.;C.M. Huang
  9. FEBS Lett. v.259 Antibacterial and antimalarial properties of peptides that are cecropin-melittin hybrids Boman, H.G.;Wade, D.;Boman, I.A.;Wahlin, B.;R.B. Merrifield
  10. FEBS Lett. v.296 Shorted cecropin A-melittin hybrids: significant size reduction retains potent antibiotic activity Andreu, D.;Ubach, J.;Boman, A.;Wahlin, B.;Wade, D.;Merrifield, R.B.;H.G. Boman
  11. Int. J. Pept. Protein. Res. v.40 Antibacterial peptides designed as analogs or hybrids of cecropins and melittin Wade, D.;Andreu, D.;Mitchell, S.A.;Silveira, A.M.W.;Boman, A.;Boman, H.G.;R.B. Merrifield
  12. J. Bacteriol. v.174 Characterization of Aspergillus nidulans mutants Deficient in Cell Wall Chitin Glucan Borgia, P.T.;C.L. Dodge
  13. J. Am. Chem. Soc. v.85 Solid phase peptides synthesis I. The synthesis of a tetrapeptide Merrifield, R.B.
  14. Rapid Commun. Mass Spectrometry. v.5 Matrixassisted laser desorption ionization with a magnetic mass spectrometer Hill, J.A.;Annan, R.S.;K. Biemann
  15. Ann. NY Acad. Sci. v.544 Anti-Candida activity and toxicology of LY121019, a novel semisynthetic polypeptide antifungal antiviotic Goedee, R.S.;Zeckner, D.J.;Howard, L.C.;Alborn, Jr., W.E.;M. Debono
  16. Kor. J. Appl. Microbiol. Bioeng. v.14 The changes of mycelial composition according to differentiation of Rhizopus oryzae Youn, H.J.;Choi, Y.K.;K.S. Cho
  17. FEMS Microbiol. Lett. v.109 Correlation of cilofungin in vivo efficacy with its activity against Aspergillus fumigatus (1,3)-β-D-glucan Synthase Beaulieu, D.;Tang, J.;Zeckner, D.J.;T.R. Parr, Jr.
  18. Biochim. Biophys. Acta. v.1063 Physicochemical determinants for the interactions of magainins 1 and 2 with acidic lipid bilayers Matsuzaki, K.;Harada, M.;Funakosi, S.;Fugii, N.;K. Miyajima
  19. Eur. J. Pharmacol. v.226 Magainin 2, a natural antibiotic from frog skin, forms ion channels in lipid bilayer membranes Cruciani, R.A.;Barker, J.L.;Durell, S.R.;Raghunathan, G.;Guy, H.R.;Zasloff, M.;E.F. Stanley
  20. Antimicrob. Agents Chemother v.35 Isolation and Characterization of Saccharomyces cerevisiae mutants Resistant to Aculeacin A Font de Mora, J.;Gil, R.;Sentandreu, R.;E. Herrero