Browse > Article
http://dx.doi.org/10.1007/s10059-009-0155-3

A Novel Antifungal Analog Peptide Derived from Protaetiamycine  

Lee, Juneyoung (School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University)
Hong, Hyun Joo (School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University)
Kim, Jin-Kyoung (Department of Bioscience and Biotechnology, Konkuk University)
Hwang, Jae-Sam (National Academy of Agricultural Science, Rural Development Administration)
Kim, Yangmee (Department of Bioscience and Biotechnology, Konkuk University)
Lee, Dong Gun (School of Life Sciences and Biotechnology, College of Natural Sciences, Kyungpook National University)
Abstract
Previously, the 9-mer analog peptides, 9Pbw2 and 9Pbw4, were designed based on a defensin-like peptide, protaetiamycine isolated from Protaetia brevitarsis. In this study, antifungal effects of the analog peptides were investigated. The antifungal susceptibility testing exhibited that 9Pbw4 contained more potent antifungal activities than 9Pbw2. A PI influx assay confirmed the effects of the analog peptides and demonstrated that the peptides exerted their activity by a membrane-active mechanism, in an energy-independent manner. As the noteworthy potency of 9Pbw4, the mechanism(s) of 9Pbw4 were further investigated. The membrane studies, using rhodamine-labeled giant unilamellar vesicle (GUV) and fluorescein isothiocyanate (FITC)-dextran loaded liposome, suggested that the membrane-active mechanism of 9Pbw4 could have originated from the pore-forming action and the radii of pores was presumed to be anywhere from 1.8 nm to 3.3 nm. These results were confirmed by 3D-flow cytometric contour-plot analysis. The present study suggests a potential of 9Pbw4 as a novel antifungal peptide.
Keywords
analog peptide; antifungal peptide; pore-forming mechanism; protaetiamycin;
Citations & Related Records
Times Cited By KSCI : 2  (Citation Analysis)
Times Cited By Web Of Science : 3  (Related Records In Web of Science)
연도 인용수 순위
1 Hancock, R.E., Brown, K.L., and Mookherjee, N. (2006). Host defence peptides from invertebrates--emerging antimicrobial strategies. Immunology 211, 315-322
2 Hwang, J., Kang, B., Kim, S.R., Yun, E., Park, K., Jeon, J.P., Nam, S., Suh, H., Hong, M.Y., and Kim, I. (2008). Molecular characterization of a defensin-like peptide from larvae of a beetle, Protaetia brevitarsis. Int. J. Ind. Entomol. 17, 131-135
3 Kontoyiannis, D.P., Mantadakis, E., and Samonis, G. (2003). Systemic mycoses in the immunocompromised host: an update in antifungal therapy. J. Hosp. Infect. 53, 243-258   DOI   ScienceOn
4 Kullberg, B.J., and de Pauw, B.E. (1999). Therapy of invasive fungal infections. Neth. J. Med. 55, 118-127   DOI   ScienceOn
5 Laurent, T.C., and Granath, K.A. (1967). Fractionation of dextran and Ficoll by chromatography on Sephadex G-200. Biochim. Biophys. Acta 136, 191-198   DOI   PUBMED   ScienceOn
6 Makovitzki, A., and Shai, Y. (2005). pH-dependent antifungal lipopeptides and their plausible mode of action. Biochemistry 44, 9775-9784   DOI   ScienceOn
7 Odds, F.C., Brown, A.J., and Gow, N.A. (2003). Antifungal agents: mechanisms of action. Trends Microbiol. 11, 272-279   DOI   ScienceOn
8 Ramani, R., Ramani, A., and Wong, S.J. (1997). Rapid flow cytometric susceptibility testing of Candida albicans. J. Clin. Microbiol. 35, 2320-2324   PUBMED
9 Rex, S. (1996). Pore formation induced by the peptide melittin in different lipid vesicle membranes. Biophys. Chem. 58, 75-85   DOI   PUBMED   ScienceOn
10 Lee, J., Choi, Y., Woo, E.R., and Lee, D.G. (2009b). Isocryptomerin, a novel membrane-active antifungal compound from Selaginella tamariscina. Biochem. Biophys. Res. Commun. 379, 676-680   DOI   ScienceOn
11 Hoffmann, J.A. (1995). Innate immunity of insects. Curr. Opin. Immunol. 7, 4-10   DOI   PUBMED   ScienceOn
12 Klein, R.S., Harris, C.A., Small, C.B., Moll, B., Lesser, M., and Friedland, G.H. (1984). Oral candidiasis in high-risk patients as the initial manifestation of the acquired immunodeficiency syndrome. N. Engl. J. Med. 311, 354-358   DOI   PUBMED   ScienceOn
13 Hopp, T.P., and Woods, K.R. (1981). Prediction of protein antigenic determinants from amino acid sequences. Proc. Natl. Acad. Sci. USA 78, 3824-3828   DOI   ScienceOn
14 Sheehan, D.J., Hitchcock, C.A., and Sibley, C.M. (1999). Current and emerging azole antifungal agents. Clin. Microbiol. Rev. 12, 40-79   PUBMED
15 Volkoff, A.N., Rocher, J., D’Alencon, E., Bouton, M., Landais, I., Quesada-Moraga, E., Vey, A., Fournier, P., Mita, K., and Devauchelle, G. (2003). Characterization and transcriptional profiles of three Spodoptera frugiperda genes encoding cysteine-rich peptides. A new class of defensin-like genes from lepidopteran insects? Gene 13, 43-53
16 Selsted, M.E., and Ouellette, A.J. (2005). Mammlian defensins in the antimicrobial immune response. Nat. Immunol. 6, 551-557   DOI   ScienceOn
17 Veerman, E.C., Valentijn-Benz, M., Nazmi, K., Ruissen, A.L., Walgreen- Weterings, E., van Marle, J., Doust, A.B., van’t Hof, W., Bolscher, J.G., and Amerongen, A.V. (2007). Energy depletion protects Candida albicans against antimicrobial peptides by rigidifying its cell membrane. J. Biol. Chem. 282, 18831-18841   DOI   ScienceOn
18 Denning, D.W. (1991). Epidemiology and pathogenesis of systemic fungal infections in the immunocompromised host. J. Antimicrob. Chemother. 28 Suppl B, 1-16   DOI
19 Mangoni, M.E., Aumelas, A., Charnet, P., Roumestand, C., Chiche, L., Despaux, E., Grassy, G., Calas, B., and Chavanieu, A. (1996). Change in membrane permeability induced by protegrin 1: implication of disulphide bridges for pore formation. FEBS Lett. 383, 93-98   DOI   PUBMED   ScienceOn
20 Zasloff, M. (2002). Antimicrobial peptides of multicellular organisms. Nature 415, 389-395   DOI   PUBMED   ScienceOn
21 Mancheno, J.M., Onaderra, M., Martinez del Pozo, A., Diaz- Achirica, P., Andreu, D., Rivas, L., and Gavilanes, J.G. (1996). Release of lipid vesicle contents by an antibacterial cecropin Amelittin hybrid peptide. Biochemistry 35, 9892-9899   DOI   ScienceOn
22 Boman, H.G. (1995). Peptide antibiotics and their role in innate immunity. Annu. Rev. Immunol. 13, 61-92   DOI   PUBMED   ScienceOn
23 Shin, S., Kim, J.K., Lee, J.Y., Jung, K.W., Hwang, J.S., Lee, J., Lee, D.G., Kim, I., Shin, S.Y., and Kim, Y. (2009). Design of potent 9- mer antimicrobial peptide analogs of protaetiamycine and investigation of mechanism of antimicrobial action. J. Pept. Sci. 15, 559-568   DOI   ScienceOn
24 Suzuki, T., Fujikura, K., Higashiyama, T., and Takata, K. (1997). DNA staining for fluorescence and laser confocal microscopy. J. Histochem. Cytochem. 45, 49-53   DOI   ScienceOn
25 Hayashi, H., and Suzuki, Y. (1998). Regulation of intracellular pH during $H^+$ coupled oligopeptide absorption in enterocytes from guinea-pig ileum. J. Physiol. 511, 573-586   DOI   ScienceOn
26 Bohrer, M.P., Deen, W.M., Robertson, C.R., Troy, J.L., and Brenner, B.M. (1979). Influence of molecular configuration on the passage of macromolecules across the glomerular capillary wall. J. Gen. Physiol. 74, 583-593   DOI   ScienceOn
27 Makovitzki, A., Avrahami, D., and Shai, Y. (2006). Ultrashort antibacterial and antifungal lipopeptides. Proc. Natl. Acad. Sci. USA 103, 15997-16002   DOI   ScienceOn
28 Jungblut, P., and Thiede, B. (1997). Protein identification from 2-DE gels by MALDI mass spectrometry. Mass Spectrom. Rev. 16, 145-162   DOI   ScienceOn
29 Lee, J.Y., Lee, S.A., Kim, J.K., Chae, C.B., and Kim, Y. (2009a). Interaction models of substrate peptides and beta-secretase studied by NMR spectroscopy and molecular dynamics simulation Mol. Cells 27, 651-656   DOI   PUBMED   ScienceOn
30 Mukherjee, P.K., Chandra, J., Kuhn, D.M., and Ghannoum, M.A. (2003). Mechanism of fluconazole resistance in Candida albicans biofilms: phase-specific role of efflux pumps and membrane sterols. Infect. Immun. 71, 4333-4340   DOI   ScienceOn
31 Zelezetsky, I., Pacor, S., Pag, U., Papo, N., Shai, Y., Sahl, H.G., and Tossi, A. (2005). Controlled alteration of the shape and conformational stability of alpha-helical cell-lytic peptides: effect on mode of action and cell specificity. Biochem. J. 390, 177-188   DOI   ScienceOn
32 Pina-Vaz, C., Sansonetty, F., Rodrigues, A.G., Costa-Oliveira, S., Tavares, C., and Martinez-de-Oliveira, J. (2001). Cytometric approach for a rapid evaluation of susceptibility of Candida strains to antifungals. Clin. Microbiol. Infect. 7, 609-618   DOI   ScienceOn
33 Ellis, M., Richardson, M., and de Pauw, B. (2000). Epidemiology. Hosp. Med. 61, 605-609   DOI
34 Lee, J., and Lee, D.G. (2009). Antifungal properties of a peptide derived from the signal peptide of the HIV-1 regulatory protein. Rev. FEBS Lett. 583, 1544-1547   DOI   ScienceOn
35 Alexander, B.D., and Perfect, J.R. (1997). Antifungal resistance trends towards the year 2000. Implications for therapy and new approaches. Drugs 54, 657-678   DOI   ScienceOn
36 Park, S.C., Kim, M.H., Hossain, M.A., Shin, S.Y., Kim, Y., Stella, L., Wade, J.D., Park, Y., and Hahm, K.S. (2008). Amphipathic alpha- helical peptide, HP (2-20), and its analogues derived from Helicobacter pylori: pore formation mechanism in various lipid compositions. Biochim. Biophys. Acta 1778, 229-241   DOI   ScienceOn
37 Park, Y., Lee, D.G., Jang, S.H., Woo, E.R., Jeong, H.G., Choi, C.H., and Hahm, K.S. (2003). A Leu-Lys-rich antimicrobial peptide: activity and mechanism. Biochim. Biophys. Acta 1645, 172-182   DOI   PUBMED   ScienceOn
38 Belokoneva, O.S., Satake, H., Mal’tseva, E.L., Pal’mina, N.P., Villegas, E., Nakajima, T., and Corzo, G. (2004). Pore formation of phospholipid membranes by the action of two hemolytic arachnid peptides of different size. Biochim. Biophys. Acta 1664, 182-188   DOI   ScienceOn
39 Gyurko, C., Lendenmann, U., Helmerhorst, E.J., Troxler, R.F., and Oppenheim, F.G. (2001). Killing of Candida albicans by histatin 5: cellular uptake and energy requirement. Antonie Van Leeuwenhoek 79, 297-309   DOI   PUBMED   ScienceOn
40 Taylor, K., Barran, P.E., and Dorin, J.R. (2008). Structure-activity relationships in beta-defensin peptides. Biopolymers 90, 1-7   DOI   PUBMED   ScienceOn
41 Wesołowska, O., Michalak, K., Maniewska, J., and Hendrich, A.B. (2009). Giant unilamellar vesicles - a perfect tool to visualize phase separation and lipid rafts in model systems. Acta Biochim. Pol. 56, 33-39   PUBMED
42 Merrifield, B. (1986). Solid phase synthesis. Science 232, 341-347   DOI   PUBMED