Lucifensins, the Insect Defensins of Biomedical Importance: The Story behind Maggot Therapy
Status PubMed-not-MEDLINE Jazyk angličtina Země Švýcarsko Médium electronic
Typ dokumentu časopisecké články
PubMed
24583934
PubMed Central
PMC3978492
DOI
10.3390/ph7030251
PII: ph7030251
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
Defensins are the most widespread antimicrobial peptides characterised in insects. These cyclic peptides, 4-6 kDa in size, are folded into α-helical/β-sheet mixed structures and have a common conserved motif of three intramolecular disulfide bridges with a Cys1-Cys4, Cys2-Cys5 and Cys3-Cys6 connectivity. They have the ability to kill especially Gram-positive bacteria and some fungi, but Gram-negative bacteria are more resistant against them. Among them are the medicinally important compounds lucifensin and lucifensin II, which have recently been identified in the medicinal larvae of the blowflies Lucilia sericata and Lucilia cuprina, respectively. These defensins contribute to wound healing during a procedure known as maggot debridement therapy (MDT) which is routinely used at hospitals worldwide. Here we discuss the decades-long story of the effort to isolate and characterise these two defensins from the bodies of medicinal larvae or from their secretions/excretions. Furthermore, our previous studies showed that the free-range larvae of L. sericata acutely eliminated most of the Gram-positive strains of bacteria and some Gram-negative strains in patients with infected diabetic foot ulcers, but MDT was ineffective during the healing of wounds infected with Pseudomonas sp. and Acinetobacter sp. The bactericidal role of lucifensins secreted into the infected wound by larvae during MDT and its ability to enhance host immunity by functioning as immunomodulator is also discussed.
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Wang G., Li X., Wang Z. APD2: The updated antimicrobial peptide database and its application in peptide design. Nucleic Acids Res. 2009;37:D933–D937. doi: 10.1093/nar/gkn823. PubMed DOI PMC
Bulet P., Hetru C., Dimarcq J.-L., Hoffmann D. Antimicrobial peptides in insects; structure and function. Dev. Comp. Immunol. 1999;23:329–344. doi: 10.1016/S0145-305X(99)00015-4. PubMed DOI
Brown K.L., Hancock R.E.W. Cationic host defense (antimicrobial) peptides. Curr. Opin. Immunol. 2006;18:24–30. doi: 10.1016/j.coi.2005.11.004. PubMed DOI
Tossi A., Sandri L., Giangaspero A. Amphipathic, α-helical antimicrobial peptides. Biopolymers. 2000;55:4–30. doi: 10.1002/1097-0282(2000)55:1<4::AID-BIP30>3.0.CO;2-M. PubMed DOI
Toke O. Antimicrobial peptides: New candidates in the fight against bacterial infections. Biopolymers. 2005;80:717–735. doi: 10.1002/bip.20286. PubMed DOI
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
Giuliani A., Pirri G., Nicoletto S.F. Antimicrobial peptides: An overview of a promising class of therapeutics. Centr. Eur. J. Biol. 2007;2:1–33. doi: 10.2478/s11535-007-0010-5. DOI
Čeřovský V., Ždárek J., Fučík V., Monincová L., Voburka Z., Bém R. Lucifensin, the long-sought antimicrobial factor of medicinal maggots of the blowfly Lucilia sericata. Cell. Mol. Life Sci. 2010;67:455–466. doi: 10.1007/s00018-009-0194-0. PubMed DOI PMC
El Shazely B., Veverka V., Fučík V., Voburka Z., Žďárek J., Čeřovský V. Lucifensin II, a defensin of medicinal maggots of the blowfly Lucilia cuprina (Diptera: Calliphoridae) J. Med. Entomol. 2013;50:571–578. doi: 10.1603/ME12208. PubMed DOI
Hoffmann J.A., Hetru C. Insect defensins: inducible antimicrobial peptides. Immunol. Today. 1992;13:411–415. doi: 10.1016/0167-5699(92)90092-L. PubMed DOI
Bulet P., Stöcklin R. Insect antimicrobial peptides: Structures, properties and gene regulation. Protein Peptide Lett. 2005;12:3–11. doi: 10.2174/0929866053406011. PubMed DOI
Sherman R.A., Hall M.J.R., Thomas S. Medicinal maggots: An ancient remedy for some contemporary afflictions. Annu. Rev. Entomol. 2000;45:55–81. doi: 10.1146/annurev.ento.45.1.55. PubMed DOI
Nigam Y., Dudley E., Bexfield A., Bond A.E., Evans J., James J. The physiology of wound healing by the medicinal maggot, Lucilia sericata. Adv. Insect Physiol. 2010;39:39–81. doi: 10.1016/B978-0-12-381387-9.00002-6. DOI
Matsuyama K., Natori S. Purification of three antibacterial proteins from the culture medium of NIH-Sape-4, an embryonic cell line of Sarcophaga peregrina. J. Biol. Chem. 1988;263:17112–17116. PubMed
Lambert J., Keppi E., Dimarcq J.-L., Wicker C., Reichhart J.-M., Dunbar B., Lepage P., Van Dorsselaer A., Hoffmann J., Forthergill J., Hoffmann D. Insect immunity: isolation from immune blood of the dipteran Phormia terranovae of two insect antibacterial peptides with sequence homology to rabbit lung macrophage bactericidal peptides. Proc. Natl. Acad. Sci. USA. 1989;86:262–266. doi: 10.1073/pnas.86.1.262. PubMed DOI PMC
Lehane M.J., Wu D., Lehane S.M. Midgut-specific immune molecules are produced by the blood-sucking insect Stomoxys calcitrans. Proc. Natl. Acad. Sci.USA. 1997;94:11502–11507. doi: 10.1073/pnas.94.21.11502. PubMed DOI PMC
Fujiwara S., Imai J., Fujiwara M., Yaeshima T., Kawashima T., Kobayashi K. A potent antimicrobial protein in royal jelly. Purification and determination of the primary structure of royalisin. J. Biol. Chem. 1990;265:11333–11337. PubMed
Rees J.A., Moniatte M., Bulet P. Novel antimicrobial peptides isolated from a European bumblebee, Bombus pascuorum (Hymenoptera, Apoidea) Insect. Biochem. Molec. Biol. 1997;27:413–422. doi: 10.1016/S0965-1748(97)00013-1. PubMed DOI
Hanzawa H., Shimada I., Kuzuhara T., Komano H., Kohda D., Inagaki F., Natori S., Arata Y. 1H nuclear magnetic resonance study of the solution conformation of an antibacterial protein, sapecin. FEBS Lett. 1990;269:413–420. doi: 10.1016/0014-5793(90)81206-4. PubMed DOI
Cornet B., Bonmatin J.-M., Hetru C., Hoffmann J.A., Ptak M., Vovelle F. Refined three-dimensional solution structure of insect defensin A. Structure. 1995;3:435–448. doi: 10.1016/S0969-2126(01)00177-0. PubMed DOI
Landon C., Sodano P., Hetru C., Hoffmann J., Ptak M. Solution structure of drosomycin, the first inducible antifungal protein from insects. Protein Sci. 1997;6:1878–1884. doi: 10.1002/pro.5560060908. PubMed DOI PMC
Mumcuoglu K. Y., Miller J., Mumcuoglu M., Friger M., Tarshis M. Destruction of bacteria in the digestive tract of the maggot of Lucilia sericata (Diptera: Calliphoridae) J. Med. Entomol. 2001;38:161–166. doi: 10.1603/0022-2585-38.2.161. PubMed DOI
Parnés A., Lagan K. M. Larval therapy in wound management: A review. Int. J. Clin. Pract. 2007;61:488–493. doi: 10.1111/j.1742-1241.2006.01238.x. PubMed DOI
Baer W.S. The treatment of chronic osteomyelitis with the maggots (larva of the blowfly) J. Bone Joint. Surg. 1931;13:438.
Simons S.W. A bactericidal principle in excretions of surgical maggots which destroys important etiological agents of pyogenic infections. J. Bacteriol. 1935;30:253–267. PubMed PMC
Pavillard E.R., Wright E.A. An antibiotic from maggots. Nature. 1957;180:916–917. doi: 10.1038/180916b0. PubMed DOI
Huberman L., Gollop N., Mumcuoglu K.Y., Breuer E., Bhusare S.R., Shai Y., Galun R. Antibacterial substances of low molecular weight isolated from the blowfly, Lucilia sericata. Med. Vet. Entomol. 2007;21:127–131. doi: 10.1111/j.1365-2915.2007.00668.x. PubMed DOI
Thomas S., Andrews A.M., Hay N.P., Bourgoise S. The anti-microbial activity of maggot secretions: results of a preliminary study. J. Tissue Viability. 1999;9:127–132. PubMed
Bexfield A., Nigam Y., Thomas S., Ratcliffe N.A. Detection and partial characterisation of two antibacterial factors from the excretions/secretions of the medicinal maggot Lucilia sericata and their activity against methicillin-resistant Staphylococcus aureus (MRSA) Microbes Infect. 2004;6:1297–1304. doi: 10.1016/j.micinf.2004.08.011. PubMed DOI
Bexfield A., Bond A.E., Roberts E.C., Dudley E., Nigam Y., Thomas S., Newton R.P., Ratcliffe N.A. The antibacterial activity against MRSA strains and other bacteria of a <500 Da fraction from maggot excretions/secretions of Lucilia sericata (Diptera: Calliphoridae) Microbes Infect. 2008;10:325–333. doi: 10.1016/j.micinf.2007.12.011. PubMed DOI
Jaklič D., Lapanje A., Zupančič K., Smrke D., Gunde-Cimerman N. Selective antimicrobial activity of maggots against pathogenic bacteria. J. Med. Microbiol. 2008;57:617–625. doi: 10.1099/jmm.0.47515-0. PubMed DOI
Kerridge A., Lappin-Scott H., Stevens J.R. Antibacterial properties of larval secretions of the blowfly, Lucilia sericata. Med. Vet. Entomol. 2005;19:333–337. doi: 10.1111/j.1365-2915.2005.00577.x. PubMed DOI
Zhang Z., Wang J., Zhang B., Liu H., Song W., He J., Lv D., Wang S., Xu X. Activity of antimicrobial protein from maggots against Staphylococcus aureus in vitro and in vivo. Int. J. Mol. Med. 2013;31:1159–1165. PubMed
Kruglikova A.A., Chernysh S.I. Antimicrobial compounds from the excretions of surgical maggots, Lucilia sericata (Meigen) (Diptera, Calliphoridae) Entomol. Rev. 2011;91:813–819. doi: 10.1134/S0013873811070013. DOI
Čeřovský V., Slaninová J., Fučík V., Monincová L., Bednárová L., Maloň P., Štokrová J. Lucifensin, a novel insect defensin of medicinal maggots: Synthesis and structural study. ChemBioChem. 2011;12:1352–1361. doi: 10.1002/cbic.201100066. PubMed DOI
Nygaard M.K.E., Andersen A.S., Kristensen H-H., Krogfelt K.A., Fojan P., Wimmer R. The insect defensin lucifensin from Lucilia sericata. J. Biomol. NMR. 2012;52:277–282. doi: 10.1007/s10858-012-9608-7. PubMed DOI
Takeuchi K., Takahashi H., Sugai M., Iwai H., Kohno T., Sekimizu K., Natori S., Shimada I. Channel-forming membrane permeabilization by an antimicrobial protein, sapecin. J. Biol. Chem. 2004;279:4981–4987. PubMed
Pymol. [(accessed on 12 February 2014)]. Available online: http://www.pymol.org/
Cociancich S., Bulet P., Hetru C., Hoffmann J.A. The inducible antimicrobial peptides of insects. Parasitol. Today. 1994;10:132–138. doi: 10.1016/0169-4758(94)90260-7. PubMed DOI
Altincicek B., Vilcinskas A. Septic injury-inducible genes in medicinal maggots of the green blow fly Lucilia sericata. Insect Mol. Biol. 2009;18:119–125. doi: 10.1111/j.1365-2583.2008.00856.x. PubMed DOI
Andersen A.S., Sandvang D., Schnorr K.M., Kruse T., Neve S., Joergensen B., Karlsmark T., Krogfelt K.A. A novel approach to the antimicrobial activity of maggot debridement therapy. J. Antimicrob. Chemother. 2010;65:1646–1654. doi: 10.1093/jac/dkq165. PubMed DOI PMC
Valachová I., Bohová J., Pálošová Z., Takáč P., Kozánek M., Majtán J. Expression of lucifensin in Lucilia sericata medicinal maggots in infected environments. Cell Tissue Res. 2013;353:165–171. doi: 10.1007/s00441-013-1626-6. PubMed DOI
Bém R., Jirkovská A., Fejfarová V., Dubský M., Skibová J., Čeřovský V. Acute antimicrobial effect of maggot therapy on diabetic foot ulcer infection as a basis for identification of antimicrobial peptides from maggots (Abstract) Diabetologia. 2010;53:56.
Bowling F.L., Salgami E.V., Boulton A.J. Larval therapy: a novel treatment in eliminating methicillin-resistant Staphylococcus aureus from diabetic foot ulcers. Diabetes Care. 2007;30:370–371. doi: 10.2337/dc06-2348. PubMed DOI
Harder J., Meyer-Hoffert U., Wehkamp K., Schwichtenberg L., Schroder J.M. Differential gene induction of human beta-defensins (hBD-1, -2, -3, and -4) in keratinocytes is inhibited by retinoic acid. J. Invest. Dermatol. 2004;123:522–529. doi: 10.1111/j.0022-202X.2004.23234.x. PubMed DOI
Khanolkar M.P., Bain S.C., Stephens J.W. The diabetic foot. QJM. 2008;101:685–695. doi: 10.1093/qjmed/hcn027. PubMed DOI
Lobmann R., Schultz G., Lehnert H. Proteases and the diabetic foot syndrome: mechanisms and therapeutic implications. Diabetes Care. 2005;28:461–471. doi: 10.2337/diacare.28.2.461. PubMed DOI
Rivas-Santiago B., Trujillo V., Montoya A., Gonzalez-Curiel I., Castaneda-Delgado J., Cardenas A., Rincon K., Hernandez M.L., Hernandez-Pando R. Expression of antimicrobial peptides in diabetic foot ulcer. J. Dermatol. Sci. 2012;65:19–26. doi: 10.1016/j.jdermsci.2011.09.013. PubMed DOI
Van der Plas M.J.A, van der Does A.M, Baldry M., Dogterom-Ballering H.C.M, van Gulpen C, van Dissel J.T., Nibbering P.H, Jukema G.N. Maggot excretions/secretions inhibit multiple neutrophil pro-inflammatory responses. Microbes Infect. 2007;9:507–514. doi: 10.1016/j.micinf.2007.01.008. PubMed DOI
Horobin A.J., Shakesheff K.M., Pritchard D.I. Promotion of human dermal fibroblast migration, matrix remodeling and modification of fibroblast morphology within a novel 3D model by Lucilia sericata larval secretions. J. Invest. Dermatol. 2006;126:1410–1418. doi: 10.1038/sj.jid.5700256. PubMed DOI
TIME management by medicinal larvae