Antimicrobial peptides (AMPs) are crucial effectors of the innate immune system. They provide the first line of defense against a variety of pathogens. AMPs display synergistic effects with conventional antibiotics, and thus present the potential for combined therapies. Insects are extremely resistant to bacterial infections. Insect AMPs are cationic and comprise less than 100 amino acids. These insect peptides exhibit an antimicrobial effect by disrupting the microbial membrane and do not easily allow microbes to develop drug resistance. Currently, membrane mechanisms underlying the antimicrobial effects of AMPs are proposed by different modes: the barrel-stave mode, toroidal-pore, carpet, and disordered toroidal-pore are the typical modes. Positive charge quantity, hydrophobic property and the secondary structure of the peptide are important for the antibacterial activity of AMPs. At present, several structural families of AMPs from insects are known (defensins, cecropins, drosocins, attacins, diptericins, ponericins, metchnikowins, and melittin), but new AMPs are frequently discovered. We reviewed the biological effects of the major insect AMPs. This review will provide further information that facilitates the study of insect AMPs and shed some light on novel microbicides.

Biomedical Research Centre University Hospital 500 03 Hradec Kralove Czech Republic

College of Life Science Yangtze University Jingzhou 434025 China

Department of Chemistry Faculty of Science University of Hradec Kralove 500 03 Hradec Kralove Czech Republic

Department of Radiology and Toxicology Faculty of Health and Social Studies University of South Bohemia 370 05 Ceske Budejovice Czech Republic

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Bulet P., Hetru C., Dimarcq J.L., Hoffmann D. Abtimicrobial peptides in insects; structure and function. Dev. Comp. Immun. 1999;23:329–344. doi: 10.1016/S0145-305X(99)00015-4. PubMed DOI

Yi H.Y., Chowdhury M., Huang Y.D., Yu X.Q. Insect antimicrobial peptides and their applications. Appl. Microbiol. Biotechnol. 2014;98:5807–5822. doi: 10.1007/s00253-014-5792-6. PubMed DOI PMC

Uccelletti D., Zanni E., Marcellini L., Palleschi C., Barra D., Mangoni M.L. Anti-Pseudomonas activity of frog skin antimicrobial peptides in a Caenorhabditis elegans infection model: A plausible mode of action in vitro and in vivo. Antimicrob. Agents Chemother. 2010;54:3853–3860. doi: 10.1128/AAC.00154-10. PubMed DOI PMC

Tonk M., Vilcinskas A., Rahnamaeian M. Insect antimicrobial peptides: Potential tools for the prevention of skin cancer. Appl. Microbiol. Biotechnol. 2016;100:7397–7405. doi: 10.1007/s00253-016-7718-y. PubMed DOI PMC

Ongey E.L., Pflugmacher S., Neubauer P. Bioinspired designs, molecular premise and tools for evaluating the ecological importance of antimicrobial peptides. Pharmaceuticals. 2018;11:68. doi: 10.3390/ph11030068. PubMed DOI PMC

Patocka J., Nepovimova E., Klimova B., Wu Q., Kuca K. Antimicrobial peptides: Amphibian host defense peptides. Curr. Med. Chem. 2018 doi: 10.2174/0929867325666180713125314. PubMed DOI

Jin G., Weinberg A. Human antimicrobial peptides and cancer. Semin. Cell Dev. Biol. 2018 doi: 10.1016/j.semcdb.2018.04.006. PubMed DOI

Kumar P., Kizhakkedathu J.N., Straus S.K. Antimicrobial peptides: Diversity, mechanism of action and strategies to improve the activity and biocompatibility in vivo. Biomolecules. 2018;8:4. doi: 10.3390/biom8010004. PubMed DOI PMC

Chernysh S., Gordya N., Suborova T. Insect antimicrobial peptide complexes prevent resistance development in bacteria. PLoS ONE. 2015;10:e0130788. doi: 10.1371/journal.pone.0130788. PubMed DOI PMC

Shen W., He P., Xiao C., Chen X. From Antimicrobial Peptides to Antimicrobial Poly(α-amino acid)s. Adv. Healthc. Mater. 2018;1:1800354. doi: 10.1002/adhm.201800354. PubMed DOI

Hollmann A., Martinez M., Maturana P., Semorile L.C., Maffia P.C. Antimicrobial peptides: Interaction with model and biological membranes and synergism with chemical antibiotics. Front. Chem. 2018;6:204. doi: 10.3389/fchem.2018.00204. PubMed DOI PMC

Jozefiak A., Engberg R.M. Insect proteins as a potential source of antimicrobial peptides in livestock production. A review. J. Anim. Feed Sci. 2017;26:87–99. doi: 10.22358/jafs/69998/2017. DOI

Bechinger B., Gorr S.U. Antimicrobial peptides: Mechanisms of action and resistance. J. Dent. Res. 2017;96:254–260. doi: 10.1177/0022034516679973. PubMed DOI PMC

Oñate-Garzón J., Manrique-Moreno M., Trier S., Leidy C., Torres R., Patiño E. Antimicrobial activity and interactions of cationic peptides derived from Galleria mellonella cecropin D-like peptide with model membranes. J. Antibiot. 2017;70:238–245. doi: 10.1038/ja.2016.134. PubMed DOI

Silvestro L., Axelsen P.H. Membrane-induced folding of cecropin A. Biophys. J. 2000;79:1465–1477. doi: 10.1016/S0006-3495(00)76398-3. PubMed DOI PMC

Yeaman M.R., Yount N.Y. Mechanisms of antimicrobial peptide action and resistance. Pharmacol. Rev. 2003;55:27–55. doi: 10.1124/pr.55.1.2. PubMed DOI

Powers J.P.S., Hancock R.E.W. The relationship between peptide structure and antibacterial activity. Peptides. 2003;24:1681–1691. doi: 10.1016/j.peptides.2003.08.023. PubMed DOI

Nan Y.H., Shin S.Y. Effect of disulphide bond position on salt resistance and LPS-neutralizing activity of α-helical homo-dimeric model antimicrobial peptides. BMB Rep. 2011;44:747–752. doi: 10.5483/BMBRep.2011.44.11.747. PubMed DOI

Yaakobi K., Liebes-Peer Y., Kushmaro A., Rapaport H. Designed amphiphilic β-sheet peptides as templates for paraoxon adsorption and detection. Langmuir. 2013;29:6840–6848. doi: 10.1021/la401280e. PubMed DOI

Freudenthal O., Quilès F., Francius G. Discrepancies between cyclic and linear antimicrobial peptide actions on the spectrochemical and nanomechanical fingerprints of a young biofilm. ACS Omega. 2017;2:5861–5872. doi: 10.1021/acsomega.7b00644. PubMed DOI PMC

Kindrachuk J., Napper S. Structure-activity relationships of multifunctional host defence peptides. Mini-Rev. Med. Chem. 2010;10:596–614. doi: 10.2174/138955710791383983. PubMed DOI

Suarez M., Haenni M., Canarelli S., Fisch F., Chodanowski P., Servis C., Michielin O., Freitag R., Moreillon P., Mermod N. Structure-function characterization and optimization of a plant-derived antibacterial peptide. Antimicrob. Agents Chemother. 2005;49:3847–3857. doi: 10.1128/AAC.49.9.3847-3857.2005. PubMed DOI PMC

McDonald M., Mannion M., Pike D., Lewis K., Flynn A., Brannan A.M., Browne M.J., Jackman D., Madera L., Power Coombs M.R., Hoskin D.W., Rise M.L., Booth V. Structure-function relationships in histidine-rich antimicrobial peptides from Atlantic cod. Biochim. Biophys. Acta. 2015;1848:1451–1461. doi: 10.1016/j.bbamem.2015.03.030. PubMed DOI

Locock K.E., Michl T.D., Valentin J.D., Vasilev K., Hayball J.D., Qu Y., Traven A., Griesser H.J., Meagher L., Haeussler M. Guanylated polymethacrylates: A class of potent antimicrobial polymers with low hemolytic activity. Biomacromolecules. 2013;14:4021–4031. doi: 10.1021/bm401128r. PubMed DOI

Leptihn S., Har J.Y., Wohland T., Ding J.L. Correlation of charge, hydrophobicity, and structure with antimicrobial activity of S1 and MIRIAM peptides. Biochemistry. 2010;49:9161–9170. doi: 10.1021/bi1011578. PubMed DOI

Naumenkova T.V., Antonov M.I.u., Nikolaev I.N., Shaĭtan K.V. Effect of Pro11-Ala11 amino acid substitution on structural and functional properties of antimicrobial peptide buforin 2. Biofizika. 2012;57:988–999. PubMed

Derache C., Meudal H., Aucagne V., Mark K.J., Cadène M., Delmas A.F., Lalmanach A.C., Landon C. Initial insights into structure-activity relationships of avian defensins. J. Biol. Chem. 2012;287:7746–7755. doi: 10.1074/jbc.M111.312108. PubMed DOI PMC

Ahn M.J., Sohn H.I., Nan Y.H., Murugan R.N., Cheong C., Ryu E.K., Kim E.H., Kang S.W., Kim E.J., Shin S.Y., et al. Functional and structural characterization of Drosocin and its derivatives linked O-GalNAc at Thr 11 residue. Bull. Korean Chem. Soc. 2011;32:3327–3332. doi: 10.5012/bkcs.2011.32.9.3327. DOI

Walkenhorst W.F., Klein J.W., Vo P., Wimley W.C. pH Dependence of microbe sterilization by cationic antimicrobial peptides. Antimicrob. Agents Chemother. 2013;57:3312–3320. doi: 10.1128/AAC.00063-13. PubMed DOI PMC

Makarova O., Johnston P., Rodriguez-Rojas A., El Shazely B., Morales J.M., Rolff J. Genomics of experimental adaptation of Staphylococcus aureus to a natural combination of insect antimicrobial peptides. Sci. Rep. 2018;8:15359. doi: 10.1038/s41598-018-33593-7. PubMed DOI PMC

Mylonakis E., Podsiadlowski L., Muhammed M., Vilcinskas A. Diversity, evolution and medical applications of insect antimicrobial peptides. Philos. Trans. R. Soc. Lond. B. 2016;371:20150290. doi: 10.1098/rstb.2015.0290. PubMed DOI PMC

Zhang L.J., Gallo R.L. Antimicrobial peptides. Curr. Biol. 2016;26:14–19. doi: 10.1016/j.cub.2015.11.017. PubMed DOI

Rozgonyi F., Szabo D., Kocsis B., Ostorházi E., Abbadessa G., Cassone M., Wade J.D., Otvos L., Jr. The antibacterial effect of a proline-rich antibacterial peptide A3-APO. Curr. Med. Chem. 2009;16:3996–4002. doi: 10.2174/092986709789352295. PubMed DOI

Ganz T., Lehrer R.I. Defensins. Pharmacol. Ther. 1995;66:191–205. doi: 10.1016/0163-7258(94)00076-F. PubMed DOI

Ganz T. Defensins: Antimicrobial peptides of innate immunity. Nat. Rev. Immunol. 2003;3:710–720. doi: 10.1038/nri1180. PubMed DOI

Thomma B.P., Cammue B.P., Thevissen K. Plant defensins. Planta. 2002;216:193–202. doi: 10.1007/s00425-002-0902-6. PubMed DOI

Zhu S., Gao B. Evolutionary origin of β-defensins. Dev. Comp. Immunol. 2013;39:79–84. doi: 10.1016/j.dci.2012.02.011. PubMed DOI

Cederlund A., Gudmundsson G.H., Agerberth B. Antimicrobial peptides important in innate immunity. FEBS J. 2011;278:3942–3951. doi: 10.1111/j.1742-4658.2011.08302.x. PubMed DOI

Tay D.K., Rajagopalan G., Li X., Chen Y., Lua L.H., Leong S.S. A new bioproduction route for a novel antimicrobial peptide. Biotechnol. Bioeng. 2011;108:572–581. doi: 10.1002/bit.22970. PubMed DOI

Hoffmann J.A., Hetru C. Insect defensins: Inducible antibacterial peptides. Immunol. Today. 1992;13:411–415. doi: 10.1016/0167-5699(92)90092-L. PubMed DOI

Hetru C., Troxler L., Hoffmann J.A. Drosophiola melanogaster antimicrobial defense. J. Infect. Dis. 2003;187:S327–S343. doi: 10.1086/374758. PubMed DOI

Gomes P.S., Fernandes M.H. Defensins in the oral cavity: Distribution and biological role. J. Oral Pathol. Med. 2010;39:1–9. doi: 10.1111/j.1600-0714.2009.00832.x. PubMed DOI

Boman H.G. Antibacterial peptides: Key components needed in immunity. Cell. 1991;65:205–207. doi: 10.1016/0092-8674(91)90154-Q. PubMed DOI

Zhao W.Y., Dong B.R., Zhou Y. In vitro antimicrobial activity of defensins from rabbit neutrophils against Pseudomonas aeruginosa and its multiple-drug-resistance strains. Sichuan Da Xue Xue Bao Yi Xue Ban. 2005;36:83–85. PubMed

Fujiwara S., Imai J., Fujiwara M., Yaeshima T., Kawashima T., Kobayashi K. A potent antibacterial protein in royal jelly. J. Biol. Chem. 1990;265:11333–11337. PubMed

Bılikova K., Gusu W., Simuth J. Isolation of a peptide fraction from honeybee royal jelly as a potential antifoulbrood factor. Apidologie. 2001;32:275–283. doi: 10.1051/apido:2001129. DOI

Steiner H., Hultmark D., Engstrom A., Bennich H., Boman H.G. Sequence and specificity of two antibacterial proteins involved in insect immunity. Nature. 1981;292:246–248. doi: 10.1038/292246a0. PubMed DOI

Hultmark D., Engström A., Bennich H., Kapur R., Boman H.G. Insect immunity. Isolation and structure of cecropin D and four minor antibacterial components from cecropia pupae. Eur. J. Biochem. 1982;127:207–217. doi: 10.1111/j.1432-1033.1982.tb06857.x. PubMed DOI

Van Hofsten P., Faye I., Kockum K., Lee J.Y., Xanthopoulos K.G., Boman I.A. Molecular cloning, cDNA sequencing, and chemical synthesis of cecropin B from Hyalophora cecropia. Proc. Nat. Acad. Sci. USA. 1985;82:2240–2243. doi: 10.1073/pnas.82.8.2240. PubMed DOI PMC

Moore A.J., Beazley W.D., Bibby M.C., Devine D.A. Antimicrobial activity of cecropins. J. Antimicrobiol. Chemother. 1996;37:1077–1089. doi: 10.1093/jac/37.6.1077. PubMed DOI

Bechinger B., Lohner K. Detergent-like actions of linear amphipathic cationic antimicrobial peptides. Biochim. Biophys. Acta. 2006;1758:1529–1539. doi: 10.1016/j.bbamem.2006.07.001. PubMed DOI

Ouyang L., Xu X., Freed S., Gao Y., Yu J., Wang S., Ju W., Zhang Y., Jin F. Cecropins from Plutella xylostella and Their Interaction with Metarhizium anisopliae. PLoS ONE. 2015;10:e0142451. doi: 10.1371/journal.pone.0142451. PubMed DOI PMC

Srisailam S., Kumar T.K.S., Arunkumar A.I., Leung K.W., Yu C., Chen H.M. Crumpled structure of the custom hydrophobic lytic peptide cecropin B3. Eur. J. Biochem. 2001;268:4278–4284. doi: 10.1046/j.1432-1327.2001.02345.x. PubMed DOI

Pillai A., Ueno S., Zhang H., Lee J.M., Kato Y. Cecropin P1 and novel nematode cecropins: A bacteria-inducible antimicrobial peptide family in the nematode Ascaris suum. Biochem. J. 2005;390:207–214. doi: 10.1042/BJ20050218. PubMed DOI PMC

Fu H., Björstad A., Dahlgren C., Bylund J. A bacterial cecropin-A peptide with a stabilized α-helical structure possess an increased killing capacity but no proinflammatory activity. Inflammation. 2004;28:337–343. doi: 10.1007/s10753-004-6644-9. PubMed DOI

Yun J., Lee D.G. Cecropin A-induced apoptosis is regulated by ion balance and glutathione antioxidant system in Candida albicans. IUBMB Life. 2016;68:652–662. doi: 10.1002/iub.1527. PubMed DOI

Durell S.R., Raghunathan G., Guy H.R. Modeling the ion channel structure of cecropin. Biophys. J. 1992;63:1623–1631. doi: 10.1016/S0006-3495(92)81730-7. PubMed DOI PMC

Lu D., Geng T., Hou C., Huang Y., Qin G., Guo X. Bombyx mori cecropin A has a high antifungal activity to entomopathogenic fungus Beauveria bassiana. Gene. 2016;583:29–35. doi: 10.1016/j.gene.2016.02.045. PubMed DOI

Srisailam S., Arunkumar A.I., Wang W., Yu C., Chen H.M. Conformational study of a custom antibacterial peptide cecropin B1: Implications of the lytic activity. Biochim. Biophys. Acta. 2000;1479:275–285. doi: 10.1016/S0167-4838(00)00008-X. PubMed DOI

Giacometti A., Cirioni O., Ghiselli R., Viticchi C., Mocchegiani F., Riva A., Saba V., Scalise G. Effect of mono-dose intraperitoneal cecropins in experimental septic shock. Crit. Care Med. 2001;29:1666–1669. doi: 10.1097/00003246-200109000-00002. PubMed DOI

Chalk R., Townson H., Ham P.J. Brugia pahangi: The effects of cecropins on microfilariae in vitro and in Aedes aegypti. Exp. Parasitol. 1995;80:401–406. doi: 10.1006/expr.1995.1052. PubMed DOI

Andrä J., Berninghausen O., Leippe M. Cecropins, antibacterial peptides from insects and mammals, are potently fungicidal against Candida albicans. Med. Microbiol. Immunol. 2001;189:169–173. doi: 10.1007/s430-001-8025-x. PubMed DOI

Hara S., Yamakawa M. A novel antibacterial peptide family isolated from the silkworm, Bombyx mori. Biochem. J. 1995;310:651–656. doi: 10.1042/bj3100651. PubMed DOI PMC

Hara S., Yamakawa M. Moricin, a novel type of antibacterial peptide isolated from the silkworm, Bombyx mori. J. Biol. Chem. 1995;270:29923–29927. PubMed

Hu H., Wang C., Guo X., Li W., Wang Y., He Q. Broad activity against porcine bacterial pathogens displayed by two insect antimicrobial peptides moricin and cecropin B. Mol. Cells. 2013;35:106–114. doi: 10.1007/s10059-013-2132-0. PubMed DOI PMC

Gudmundsson G.H., Lidholm D.A., Asling B., Gan R., Boman H.G. The cecropin locus. Cloning and expression of a gene cluster encoding three antibacterial peptides in Hyalophora cecropia. J. Biol. Chem. 1991;266:11510–11517. PubMed

Guo C., Huang Y., Zheng H., Tang L., He J., Xiao L., Liu D., Jiang H. Secretion and activity of antimicrobial peptide cecropin D expressed in Pichia pastoris. Exp. Ther. Med. 2012;4:1063–1068. doi: 10.3892/etm.2012.719. PubMed DOI PMC

Park S.I., An H.S., Chang B.S., Yoe S.M. Expression, cDNA cloning, and characterization of the antibacterial peptide cecropin D from Agrius convolvuli. Anim. Cells Syst. 2013;17:23–30. doi: 10.1080/19768354.2013.769465. DOI

Liu X., Guo C., Huang Y., Zhang X., Chen Y. Inhibition of porcine reproductive and respiratory syndrome virus by Cecropin D in vitro. Infect. Genet. Evol. 2015;34:7–16. doi: 10.1016/j.meegid.2015.06.021. PubMed DOI

Hou Z.P., Wang W.J., Liu Z.Q., Liu G., Souffrant W.B., Yin Y.L. Effect of lactoferricin B and cecropin P1 against enterotoxigenic Escherichia coli in vitro. J. Food Agric. Environ. 2011;9:271–274.

Baek M.H., Kamiya M., Kushibiki T., Nakazumi T., Tomisawa S., Abe C., Kumaki Y., Kikukawa T., Demura M., Kawano K., et al. Lipopolysaccharide-bound structure of the antimicrobial peptide cecropin P1 determined by nuclear magnetic resonance spectroscopy. J. Pept. Sci. 2016;22:214–221. doi: 10.1002/psc.2865. PubMed DOI

Arcidiacono S., Soares J.W., Meehan A.M., Marek P., Kirby R. Membrane permeability and antimicrobial kinetics of cecropin P1 against Escherichia coli. J. Pept. Sci. 2009;15:398–403. doi: 10.1002/psc.1125. PubMed DOI

Wu X., Wei P.H., Zhu X., Wirth M.J., Bhunia A., Narsimhan G. Effect of immobilization on the antimicrobial activity of a cysteine-terminated antimicrobial Peptide Cecropin P1 tethered to silica nanoparticle against E. coli O157:H7 E.D.L. Colloids Surf. B Biointerfaces. 2017;156:305–312. doi: 10.1016/j.colsurfb.2017.05.047. PubMed DOI

Zakharchenko N.S., Belous A.S., Biryukova Y.K., Medvedeva OA., Belyakova A.V., Masgutova G.A., Trubnikova E.V., Buryanov Y.I., Lebedeva A.A. Immunomodulating and Revascularizing Activity of Kalanchoe pinnata Synergize with Fungicide Activity of Biogenic Peptide Cecropin P1. J. Immunol. Res. 2017;2017:3940743. doi: 10.1155/2017/3940743. PubMed DOI PMC

Guo C., Huang Y., Cong P., Liu X., Chen Y., He Z. Cecropin P1 inhibits porcine reproductive and respiratory syndrome virus by blocking attachment. BMC Microbiol. 2014;14:273. doi: 10.1186/s12866-014-0273-8. PubMed DOI PMC

Wang Z., Han X., He N., Chen Z., Brooks C.L., 3rd Molecular structures of C- and N-terminus cysteine modified cecropin P1 chemically immobilized onto maleimide-terminated self-assembled monolayers investigated by molecular dynamics simulation. J. Phys. Chem. B. 2014;118:5670–5680. doi: 10.1021/jp5023482. PubMed DOI

Téllez G.A., Castaño-Osorio J.C. Expression and purification of an active cecropin-like recombinant protein against multidrug resistance Escherichia coli. Protein Expr. Purif. 2014;100:48–53. doi: 10.1016/j.pep.2014.05.004. PubMed DOI

Lu X., Shen J., Jin X., Ma Y., Huang Y., Mei H., Chu F., Zhu J. Bactericidal activity of Musca domestica cecropin (Mdc) on multidrug-resistant clinical isolate of Escherichia coli. Appl. Microbiol. Biotechnol. 2012;95:939–945. doi: 10.1007/s00253-011-3793-2. PubMed DOI

Hultmark D., Engström A., Andersson K., Steiner H., Bennich H., Boman H.G. Insect immunity. Attacins, a family of antibacterial proteins from Hyalophora cecropia. EMBO J. 1983;2:571–576. doi: 10.1002/j.1460-2075.1983.tb01465.x. PubMed DOI PMC

Carlsson A., Engström P., Palva E.T., Bennich H. Attacin, an antibacterial protein from Hyalophora cecropia, inhibits synthesis of outer membrane proteins in Escherichia coli by interfering with omp gene transcription. Infect. Immun. 1991;59:3040–3045. PubMed PMC

Carlsson A., Nyström T., de Cock H., Bennich H. Attacin—An insect immune protein—Binds LPS and triggers the specific inhibition of bacterial outer-membrane protein synthesis. Microbiology. 1998;144:2179–2188. doi: 10.1099/00221287-144-8-2179. PubMed DOI

Kockum K., Faye I., Hofsten P.V., Lee J.Y., Xanthopoulos K.G., Boman H.G. Insect immunity. Isolation and sequence of two cDNA clones corresponding to acidic and basic attacins from Hyalophora cecropia. EMBO J. 1984;3:2071–2075. doi: 10.1002/j.1460-2075.1984.tb02093.x. PubMed DOI PMC

Dushay M.S., Roethele J.B., Chaverri J.M., Dulek D.E., Syed S.K., Kitami T., Eldon E.D. Two attacin antibacterial genes of Drosophila melanogaster. Gene. 2000;246:49–57. doi: 10.1016/S0378-1119(00)00041-X. PubMed DOI

Geng H., An C.J., Hao Y.J., Li D.S., Du R.Q. Molecular cloning and expression of Attacin from housefly (Musca domestica) Yi Chuan Xue Bao. 2004;31:1344–1350. PubMed

Liu G., Kang D., Steiner H. Trichoplusia ni lebocin, an inducible immune gene with a downstream insertion element. Biochem. Biophys. Res. Commun. 2000;269:803–807. doi: 10.1006/bbrc.2000.2366. PubMed DOI

Casteels P., Ampe C., Riviere L., Van Damme J., Elicone C., Fleming M., Jacobs F., Tempst P. Isolation and characterization of abaecin, a major antibacterial response peptide in the honeybee (Apis mellifera) Eur. J. Biochem. 1990;187:381–386. doi: 10.1111/j.1432-1033.1990.tb15315.x. PubMed DOI

Slocinska M., Marciniak P., Rosinski G. Insects antiviral and anticancer peptides: New leads for the future? Protein Pept. Lett. 2008;15:578–585. doi: 10.2174/092986608784966912. PubMed DOI

Bulet P., Dimarcq J.L., Hetru C., Lagueux M., Charlet M., Hegy G., Van Dorsselaer A., Hoffmann J.A. A novel inducible antibacterial peptide of Drosophila carries an O-glycosylated substitution. J. Biol. Chem. 1993;268:14893–14897. PubMed

McManus A.M., Otvos L., Jr., Hoffmann R., Craik D.J. Conformational studies by NMR of the antimicrobial peptide, drosocin, and its non-glycosylated derivative: Effects of glycosylation on solution conformation. Biochemistry. 1999;38:705–714. doi: 10.1021/bi981956d. PubMed DOI

Lele D.S., Talat S., Kumari S., Srivastava N., Kaur K.J. Understanding the importance of glycosylated threonine and stereospecific action of Drosocin, a Proline rich antimicrobial peptide. Eur. J. Med. Chem. 2015;92:637–647. doi: 10.1016/j.ejmech.2015.01.032. PubMed DOI

Bulet P., Urge L., Ohresser S., Hetru C., Otvos L., Jr. Enlarged scale chemical synthesis and range of activity of drosocin, an O-glycosylated antibacterial peptide of Drosophila. Eur. J. Biochem. 1996;238:64–69. doi: 10.1111/j.1432-1033.1996.0064q.x. PubMed DOI

Imler J.L., Bulet P. Antimicrobial peptides in Drosophila: Structures, activities and gene regulation. Chem. Immunol. Allergy. 2005;86:1–21. PubMed

Gobbo M., Biondi L., Filira F., Gennaro R., Benincasa M., Scolaro B., Rocchi R. Antimicrobial peptides: Synthesis and antibacterial activity of linear and cyclic drosocin and apidaecin 1b analogues. J. Med. Chem. 2002;45:4494–4504. doi: 10.1021/jm020861d. PubMed DOI

Matsumoto K., Orikasa Y., Ichinohe K., Hashimoto S., Ooi T., Taguchi S. Flow cytometric analysis of the contributing factors for antimicrobial activity enhancement of cell-penetrating type peptides: Case study on engineered apidaecins. Biochem. Biophys. Res. Commun. 2010;395:7–10. doi: 10.1016/j.bbrc.2010.03.088. PubMed DOI

Bluhm M.E., Schneider V.A., Schäfer I., Piantavigna S., Goldbach T., Knappe D., Seibel P., Martin L.L., Veldhuizen E.J., Hoffmann R. N-Terminal Ile-Orn- and Trp-Orn-Motif Repeats Enhance Membrane Interaction and Increase the Antimicrobial Activity of Apidaecins against Pseudomonas aeruginosa. Front. Cell Dev. Biol. 2016;4:39. doi: 10.3389/fcell.2016.00039. PubMed DOI PMC

Cudic M., Bulet P., Hoffmann R., Craik D.J., Otvos L., Jr. Chemical synthesis, antibacterial activity and conformation of diptericin, an 82-mer peptide originally isolated from insects. Eur. J. Biochem. 1999;266:549–558. doi: 10.1046/j.1432-1327.1999.00894.x. PubMed DOI

Dimarcq J.L., Keppi E., Dunbar B., Lambert J., Reichhart J.M., Hoffmann D., Rankine S.M., Fothergill J.E., Hoffmann J.A. Insect immunity. Purification and characterization of a family of novel inducible antibacterial proteins from immunized larvae of the dipteran Phormia terranovae and complete amino-acid sequence of the predominant member, diptericin A. Eur. J. Biochem. 1988;171:17–22. doi: 10.1111/j.1432-1033.1988.tb13752.x. PubMed DOI

Reichhart J.M., Meister M., Dimarcq J.L., Zachary D., Hoffmann D., Ruiz C., Richards G., Hoffmann J.A. Insect immunity: Developmental and inducible activity of the Drosophila diptericin promoter. EMBO J. 1992;11:1469–1477. doi: 10.1002/j.1460-2075.1992.tb05191.x. PubMed DOI PMC

Ishikawa M., Kubo T., Natori S. Purification and characterization of a diptericin homologue from Sarcophaga peregrina (flesh fly) Biochem. J. 1992;287:573–578. doi: 10.1042/bj2870573. PubMed DOI PMC

Keppi E., Pugsley A.P., Lambert J., Wicker C., Dimarcq J.L., Hoffmann J.A., Hoffmann D. Mode of action of diptericin A, a bactericidal peptide induced in the hemolymph of Phormia terranovae larvae. Insect Biochem. Physiol. 1989;10:229–239. doi: 10.1002/arch.940100306. DOI

Ursic-Bedoya R., Buchhop J., Joy J.B., Durvasula R., Lowenberger C. Prolixicin: A novel antimicrobial peptide isolated from Rhodnius prolixus with differential activity against bacteria and Trypanosoma cruzi. Insect Mol. Biol. 2011;20:775–786. doi: 10.1111/j.1365-2583.2011.01107.x. PubMed DOI

Levashina E.A., Ohresser S., Bulet P., Reichhart J.M., Hetru C., Hoffmann J.A. Metchnikowin, a novel immune-inducible proline-rich peptide from Drosophila with antibacterial and antifungal properties. Eur. J. Biochem. 1995;233:694–700. doi: 10.1111/j.1432-1033.1995.694_2.x. PubMed DOI

Levashina E.A., Ohresser S., Lemaitre B., Imler J.L. Two distinct pathways can control expression of the gene encoding the Drosophila antimicrobial peptide metchnikowin. J. Mol. Biol. 1998;278:515–527. doi: 10.1006/jmbi.1998.1705. PubMed DOI

Moghaddam M.R.B., Gross T., Becker A., Vilcinskas A., Rahnamaeian M. The selective antifungal activity of Drosophila melanogaster metchnikowin reflects the speciesdependent inhibition of succinate-coenzyme Q reductase. Sci. Rep. 2017;7:8192. doi: 10.1038/s41598-017-08407-x. PubMed DOI PMC

Orivel J., Redeker V., Le Caer J.P., Krier F., Revol-Junelles A.M., Longeon A., Chaffotte A., Dejean A., Rossier J. Ponericins, new antibacterial and insecticidal peptides from the venom of the ant Pachycondyla goeldii. J. Biol. Chem. 2001;276:17823–17829. doi: 10.1074/jbc.M100216200. PubMed DOI

Johnson S.R., Copello J.A., Evans M.S., Suarez A.V. A biochemical characterization of the major peptides from the Venom of the giant Neotropical hunting ant Dinoponera australis. Toxicon. 2010;55:702–710. doi: 10.1016/j.toxicon.2009.10.021. PubMed DOI

Romanelli A., Moggio L., Montella R.C., Campiglia P., Iannaccone M., Capuano F., Pedone C., Capparelli R. Peptides from Royal Jelly: Studies on the antimicrobial activity of jelleins, jelleins analogs and synergy with temporins. J. Pept. Sci. 2011;17:348–352. doi: 10.1002/psc.1316. PubMed DOI

Fontana R., Mendes M.A., de Souza B.M., Konno K., César L.M., Malaspina O., Palma M.S. elleines: A family of antimicrobial peptides from the Royal Jelly of honeybees (Apis mellifera) Peptides. 2004;5:919–928. doi: 10.1016/j.peptides.2004.03.016. PubMed DOI

Jia F., Wang J., Peng J, Zhao P., Kong Z., Wang K., Yan W., Wang R. The in vitro, in vivo antifungal activity and the action mode of Jelleine-I against Candida species. Amino Acids. 2018;50:229–239. doi: 10.1007/s00726-017-2507-1. PubMed DOI

Barnutiu L.I., Marghitas L.A., Dezmirean D.S., Bobis O., Mihai C.M., Pavel C. Antimicrobial compounds of Royal Jelly. Bull. Univ. Agric. Sci. Vet. Med. Cluj-Napoca. 2011;68:85–90.

Bilikova K., Hanes J., Nordhoff E., Saenger W., Klaudiny J., Simuth J. Apisimin. A new serine-valine-rich peptide from honeybee (Apis mellifera L.) royal jelly: Purification and molecular characterization. FEBS Lett. 2002;528:125–129. doi: 10.1016/S0014-5793(02)03272-6. PubMed DOI

Shen L.L., Xing Y.Y., Gao Q. Sequence analysis of functional Apisimin-2 cDNA from royal jelly of Chinese honeybee and its expression in Escherichia coli. Asia Pac. J. Clin. Nutr. 2007;16:222–226. PubMed

Gannabathula S., Krissansen G.W., Skinner M., Steinhorn G., Schlothauer R. Honeybee apisimin and plant arabinogalactans in honey costimulate monocytes. Food Chem. 2015;168:34–40. doi: 10.1016/j.foodchem.2014.07.007. PubMed DOI

Cociancich S., Dupont A., Hegy G., Lanot R., Holder F., Hetru C., Hoffmann J.A., Bulet P. Novel inducible antibacterial peptides from a hemipteran insect, the sap-sucking bug Pyrrhocoris apterus. Biochem. J. 1994;300:567–575. doi: 10.1042/bj3000567. PubMed DOI PMC

Kragol G., Lovas S., Varadi G., Condie B.A., Hoffmann R., Otvos L., Jr. The antibacterial peptide pyrrhocoricin inhibits the ATPase actions of DnaK and prevents chaperone-assisted protein folding. Biochemistry. 2001;40:3016–3026. doi: 10.1021/bi002656a. PubMed DOI

Chesnokova L.S., Slepenkov S.V., Witt S.N. The insect antimicrobial peptide, L-pyrrhocoricin, binds to and stimulates the ATPase activity of both wild-type and lidless DnaK. FEBS Lett. 2004;565:65–69. doi: 10.1016/j.febslet.2004.03.075. PubMed DOI

Kragol G., Hoffmann R., Chattergoon M.A., Lovas S., Cudic M., Bulet P., Condie B.A., Rosengren K.J., Montaner L.J., Otvos L., Jr. Identification of crucial residues for the antibacterial activity of the proline-rich peptide, pyrrhocoricin. Eur. J. Biochem. 2002;269:4226–4237. doi: 10.1046/j.1432-1033.2002.03119.x. PubMed DOI

Boxell A., Lee S.H., Jefferies R., Watt P., Hopkins R., Reid S., Armson A., Ryan U. Pyrrhocoricin as a potential drug delivery vehicle for Cryptosporidium parvum. Exp. Parasitol. 2008;119:301–303. doi: 10.1016/j.exppara.2008.02.005. PubMed DOI

Rosengren K.J., Göransson U., Otvos L., Jr., Craik D.J. Cyclization of pyrrhocoricin retains structural elements crucial for the antimicrobial activity of the native peptide. Biopolymers. 2004;76:446–458. doi: 10.1002/bip.20159. PubMed DOI

Saito Y., Konnai S., Yamada S., Imamura S., Nishikado H., Ito T., Onuma M., Ohashi K. Identification and characterization of antimicrobial peptide, defensin, in the taiga tick, Ixodes persulcatus. Insect Mol. Biol. 2009;18:531–539. doi: 10.1111/j.1365-2583.2009.00897.x. PubMed DOI

Rudenko N., Golovchenko M., Grubhoffer L. Gene organization of a novel defensin of Ixodes ricinus: First annotation of an intron/exon structure in a hard tick defensin gene and first evidence of the occurrence of two isoforms of one member of the arthropod defensin family. Insect Mol. Biol. 2007;16:501–507. doi: 10.1111/j.1365-2583.2007.00745.x. PubMed DOI

Tsuji N., Battsetseg B., Boldbaatar D., Miyoshi T., Xuan X., Oliver J.H., Jr., Fujisaki K. Babesial vector tick defensin against Babesia sp. parasites. Infect. Immun. 2007;75:3633–3640. doi: 10.1128/IAI.00256-07. PubMed DOI PMC

Miyoshi N., Isogai E., Hiramatsu K., Sasaki T. Activity of tick antimicrobial peptide from Ixodes persulcatus (persulcatusin) against cell membranes of drug-resistant Staphylococcus aureus. J. Antibiot. 2017;70:142–146. doi: 10.1038/ja.2016.101. PubMed DOI

Miyoshi N., Saito T., Ohmura T., Kuroda K., Suita K., Ihara K., Isogai E. Functional structure and antimicrobial activity of persulcatusin, an antimicrobial peptide from the hard tick Ixodes persulcatus. Parasites Vectors. 2016;9:85. doi: 10.1186/s13071-016-1360-5. PubMed DOI PMC

Jamasbi E., Lucky S.S., Li W., Hossain M.A., Gopalakrishnakone P., Separovic F. Effect of dimerized melittin on gastric cancer cells and antibacterial activ ity. Amino Acids. 2018 doi: 10.1007/s00726-018-2587-6. PubMed DOI

Chen J., Guan S.M., Sun W., Fu H. Melittin, the major pain-producing substance of bee venom. Neurosci. Bull. 2016;32:265–272. doi: 10.1007/s12264-016-0024-y. PubMed DOI PMC

Lee G., Bae H. Anti-Inflammatory applications of melittin, a major component of bee venom: Detailed mechanism of action and adverse effects. Molecules. 2016;21:E616. doi: 10.3390/molecules21050616. PubMed DOI PMC

Socarras K.M., Theophilus P.A.S., Torres J.P., Gupta K., Sapi E. Antimicrobial activity of bee venom and melittin against borrelia burgdorferi. Antibiotics. 2017;6:31. doi: 10.3390/antibiotics6040031. PubMed DOI PMC

Wu X., Singh A.K., Wu X., Lyu Y., Bhunia A.K., Narsimhan G. Characterization of antimicrobial activity against Listeria and cytotoxicity of native melittin and its mutant variants. Colloids. Surf. B Biointerfaces. 2016;143:194–205. doi: 10.1016/j.colsurfb.2016.03.037. PubMed DOI

Leandro L.F., Mendes C.A., Casemiro L.A., Vinholis A.H., Cunha W.R., de Almeida R., Martins C.H. Antimicrobial activity of apitoxin, melittin and phospholipase A₂ of honey bee (Apis mellifera) venom against oral pathogens. Anais Acad. Bras. Ciênc. 2015;87:147–155. doi: 10.1590/0001-3765201520130511. PubMed DOI

Picoli T., Peter C.M., Zani J.L., Waller S.B., Lopes M.G., Boesche K.N., Vargas G.D.Á., Hübner S.O., Fischer G. Melittin and its potential in the destruction and inhibition of the biofilm formation by Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa isolated from bovine milk. Microb. Pathog. 2017;112:57–62. doi: 10.1016/j.micpath.2017.09.046. PubMed DOI

Shi W., Li C., Li M., Zong X., Han D., Chen Y. Antimicrobial peptide melittin against Xanthomonas oryzae pv. oryzae, the bacterial leaf blight pathogen in rice. Appl. Microbiol. Biotechnol. 2016;100:5059–5067. doi: 10.1007/s00253-016-7400-4. PubMed DOI PMC

Zhang S.K., Ma Q., Li S.B., Gao H.W., Tan Y.X., Gong F., Ji S.P. RV-23, a melittin-related peptide with cell-selective antibacterial activity and high hemocompatibility. J. Microbiol. Biotechnol. 2016;26:1046–1056. doi: 10.4014/jmb.1510.10074. PubMed DOI

Wiedman G., Fuselier T., He J., Searson P.C., Hristova K., Wimley W.C. Highly efficient macromolecule-sized poration of lipid bilayers by a synthetically evolved peptide. J. Am. Chem. Soc. 2014;136:4724–4731. doi: 10.1021/ja500462s. PubMed DOI PMC

Rady I., Siddiqui I.A., Rady M., Mukhtar H. Melittin, a major peptide component of bee venom, and its conjugates in cancer therapy. Cancer Lett. 2017;402:16–31. doi: 10.1016/j.canlet.2017.05.010. PubMed DOI PMC

Jamasbi E., Mularski A., Separovic F. Model membrane and cell studies of antimicrobial activity of melittin analogues. Curr. Top. Med. Chem. 2016;16:40–45. doi: 10.2174/1568026615666150703115919. PubMed DOI

Wimley W.C. How does melittin permeabilize membranes? Biophys. J. 2018;114:251–253. doi: 10.1016/j.bpj.2017.11.3738. PubMed DOI PMC

Lee M.T., Sun T.L., Hung W.C., Huang H.W. Process of inducing pores in membranes by melittin. Proc. Natl. Acad. Sci. USA. 2013;110:14243–14248. doi: 10.1073/pnas.1307010110. PubMed DOI PMC

Wiedman G., Herman K., Searson P., Wimley W.C., Hristova K. The electrical response of bilayers to the bee venom toxin melittin: Evidence for transient bilayer permeabilization. Biochim. Biophys. Acta-Biomembr. 2013;1828:1357–1364. doi: 10.1016/j.bbamem.2013.01.021. PubMed DOI PMC

Lee J., Lee D.G. Melittin triggers apoptosis in Candida albicans through the reactive oxygen species-mediated mitochondria/caspasedependent pathway. FEMS Microbiol. Lett. 2014;355:36–42. doi: 10.1111/1574-6968.12450. PubMed DOI

Akbari R., Hakemi Vala M., Pashaie F., Bevalian P., Hashemi A., Pooshang Bagheri K. Highly synergistic effects of melittin with conventional antibiotics against multidrug-resistant isolates of acinetobacter baumannii and pseudomonas aeruginosa. Microb. Drug Resist. 2018 doi: 10.1089/mdr.2018.0016. PubMed DOI

Akbari R., Hakemi Vala M., Hashemi A., Aghazadeh H., Sabatier J.M., Pooshang Bagheri K. Action mechanism of melittin-derived antimicrobial peptides, MDP1 and MDP2, de novo designed against multidrug resistant bacteria. Amino Acids. 2018;50:1231–1243. doi: 10.1007/s00726-018-2596-5. PubMed DOI

Choi J.H., Jang A.Y., Lin S., Lim S., Kim D., Park K., Han S.M., Yeo J.H., Seo H.S. Melittin, a honeybee venom-derived antimicrobial peptide, may target methicillin-resistant Staphylococcus aureus. Mol. Med. Rep. 2015;12:6483–6490. doi: 10.3892/mmr.2015.4275. PubMed DOI PMC

Moreno M., Giralt E. Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: Melittin, apamin and mastoparan. Toxins. 2015;7:1126–1150. doi: 10.3390/toxins7041126. PubMed DOI PMC

Zhang Q., Hou C., Shamsi I.H., Ali E., Muhammad N., Shah J.M., Abid A.A. Identification of super antibiotic-resistant bacteria in diverse soils. Int. J. Agric. Biol. 2015;17:1133–1140. doi: 10.17957/IJAB/15.0047. DOI

Lee J.K., Luchian T., Park Y. New antimicrobial peptide kills drug-resistant pathogens without detectable resistance. Oncotarget. 2018;9:15616–15634. doi: 10.18632/oncotarget.24582. PubMed DOI PMC

Wu X., Li Z., Li X., Tian Y., Fan Y., Yu C., Zhou B., Liu Y., Xiang R., Yang L. Synergistic effects of antimicrobial peptide DP7 combined with antibiotics against multidrug-resistant bacteria. Drug Des. Devel. Ther. 2017;11:939–946. doi: 10.2147/DDDT.S107195. PubMed DOI PMC

Zerweck J., Strandberg E., Burck J. Reichert, J.; Wadhwani, P.; Kukharenko, O.; Ulrich, A.S. Homo- and heteromeric interaction strengths of the synergistic antimicrobial peptides PGLa and magainin 2 in membranes. Eur. Biophys. J. Biophy. Lett. 2016;45:535–547. doi: 10.1007/s00249-016-1120-7. PubMed DOI

Biswaro L.S., da Costa Sousa M.G., Rezende T.M.B., Dias S.C., Franco O.L. Antimicrobial peptides and nanotechnology, recent advances and challenges. Front. Microbiol. 2018;9:855. doi: 10.3389/fmicb.2018.00855. PubMed DOI PMC

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