Lucifensin, the long-sought antimicrobial factor of medicinal maggots of the blowfly Lucilia sericata

Čeřovský, Václav; Žďárek, Jan; Fučı́k, Vladimı́r; Monincová, Lenka; Vobůrka, Zdeněk; Bém, Robert

doi:10.1007/s00018-009-0194-0

Cited by 133 publications

(82 citation statements)

References 24 publications

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“…[16] Later, the production of recombinant peptide resulting in a few milligrams of active peptide was reported by Andersen. [17] Although, numerous synthetic studies in the expanding field of defensins have been published during the last two decades, only a few of these papers report the synthesis of insect defensins.…”

Section: Discussionmentioning

confidence: 98%

“…We supposed that the three-dimensional structure of lucifensin is similar to that of sapecin, [30] because the primary sequence of sapecin (40 residues) differs from the sequence of lucifensin by only four amino acid residues (Ile11, Asn12, Lys33, Val35). The conformation of sapecin was determined by 1 H NMR spectroscopy and simulated annealing calculations, [30] resulting in a structure that includes an N-terminal flexible loop (residues 4-12), a helical part (residues [15][16][17][18][19][20][21][22][23], and an antiparallel b-structure (residues 24-31 and 34-40). Significant antimicrobial activity of the Luc[C16-C36] analogue against the most sensitive bacterium M. luteus (Figure 7 A) in comparison with the other two analogues containing one disulfide bridge clearly indicates that the disulfide bond between Cys16 and Cys36, which connects the 15-23 helical part of the molecule with the 34-40 strand is the most important one for maintaining the ordered structure of lucifensin.…”

Section: Discussionmentioning

confidence: 99%

“…[13][14][15] Surprisingly, the structural characterization of Lucilia defensin had not been reported until 2010, when we purified lucifensin from an extract of larval guts, determined its structure by mass spectrometry and Edman degradation ( Figure 1), and then identified it in other larval tissues as well as in the larval ES. [16] Soon after, the primary sequence…”

Section: Introductionmentioning

confidence: 98%

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Lucifensin, a Novel Insect Defensin of Medicinal Maggots: Synthesis and Structural Study

et al. 2011

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Recently, we identified a new insect defensin, named lucifensin that is secreted/excreted by the blowfly Lucilia sericata larvae into a wound as a disinfectant during the medicinal process known as maggot therapy. Here, we report the total chemical synthesis of this peptide of 40 amino acid residues and three intramolecular disulfide bridges by using three different protocols. Oxidative folding of linear peptide yielded a peptide with a pattern of disulfide bridges identical to that of native lucifensin. The synthetic lucifensin was active against Gram-positive bacteria and was not hemolytic. We synthesized three lucifensin analogues that are cyclized through one native disulfide bridge in different positions and having the remaining four cysteines substituted by alanine. Only the analogue cyclized through a Cys16-Cys36 disulfide bridge showed weak antimicrobial activity. Truncating lucifensin at the N-terminal by ten amino acid residues resulted in a drop in antimicrobial activity. Linear lucifensin having all six cysteine residues alkylated was inactive. Circular dichroism spectra measured in the presence of α-helix-promoting compounds showed different patterns for lucifensin and its analogues. Transmission electron microscopy revealed that Bacillus subtilis treatment with lucifensin induced significant changes in its envelope.

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Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Lucifensin, a Novel Insect Defensin of Medicinal Maggots: Synthesis and Structural Study

et al. 2011

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“…The therapeutic effects include the removal of necrotic tissue (debridement), the acceleration of wound healing, and wound disinfection (5,6). The wound disinfection property has been attributed to antimicrobial components in the larval secretions, including small molecules with antibacterial activity (7,8) and antimicrobial peptides (AMPs), such as the defensin-like lucifensin (9) and a recently reported AMP with potent antifungal activity, which accordingly was named lucimycin (10).…”

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confidence: 99%

Antimicrobial Peptides Expressed in Medicinal Maggots of the Blow Fly Lucilia sericata Show Combinatorial Activity against Bacteria

Pöppel

Vogel

Wiesner

et al. 2015

Antimicrob Agents Chemother

138

108

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The larvae of the common green bottle fly (Lucilia sericata) produce antibacterial secretions that have a therapeutic effect on chronic and nonhealing wounds. Recent developments in insect biotechnology have made it possible to use these larvae as a source of novel anti-infectives. Here, we report the application of next-generation RNA sequencing (RNA-Seq) to characterize the transcriptomes of the larval glands, crop, and gut, which contribute to the synthesis of antimicrobial peptides (AMPs) and proteins secreted into wounds. Our data confirm that L. sericata larvae have adapted in order to colonize microbially contaminated habitats, such as carrion and necrotic wounds, and are protected against infection by a diverse spectrum of AMPs. L. sericata AMPs include not only lucifensin and lucimycin but also novel attacins, cecropins, diptericins, proline-rich peptides, and sarcotoxins. We identified 47 genes encoding putative AMPs and produced 23 as synthetic analogs, among which some displayed activities against a broad spectrum of microbial pathogens, including Pseudomonas aeruginosa, Proteus vulgaris, and Enterococcus faecalis. Against Escherichia coli (Gram negative) and Micrococcus luteus (Gram positive), we found mostly additive effects but also synergistic activity when selected AMPs were tested in combination. The AMPs that are easy to synthesize are currently being produced in bulk to allow their evaluation as novel anti-infectives that can be formulated in hydrogels to produce therapeutic wound dressings and adhesive bandages.T he larvae of the common green bottle fly Lucilia sericata, a member of the blow fly family (Calliphoridae), are known as medical maggots or wound maggots, because they have been used to treat wounds as part of traditional medicine (1). This approach, commonly termed maggot therapy, is an approved and prospering alternative for the treatment of chronic and nonhealing wounds, e.g., those associated with diabetic ulcers (2-4). The therapeutic effects include the removal of necrotic tissue (debridement), the acceleration of wound healing, and wound disinfection (5, 6). The wound disinfection property has been attributed to antimicrobial components in the larval secretions, including small molecules with antibacterial activity (7, 8) and antimicrobial peptides (AMPs), such as the defensin-like lucifensin (9) and a recently reported AMP with potent antifungal activity, which accordingly was named lucimycin (10).The ability of L. sericata larvae to prosper on carrion and necrotic wounds suggests that they are adapted to colonize contaminated environments, e.g., by expressing a diverse spectrum of AMPs to protect them against the microbes they encounter (11). This theory is supported by the unique ability of rat-tailed maggots (larvae of the drone fly Eristalis tenax) to survive in highly contaminated aquatic habitats, such as liquid manure storage pits and cesspools, which also reflects their production of multiple diverse AMPs (12). Similarly, we found that the burying beetle Nicrophorus ...

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“…Lucifensin was first purified in 2010 from an extract of the gut of L. sericacta larvae by Čeřovský et al [142]. They showed that the peptide contained 40 amino acid residues and 3 disulphide bridges and was a typical 4 kDa dipteran defensin.…”

Section: Maggot Moleculesmentioning

confidence: 99%

Recent Advances in Developing Insect Natural Products as Potential Modern Day Medicines

Ratcliffe

Azambuja

Mello

2014

Evidence-Based Complementary and Alternative Medicine

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Except for honey as food, and silk for clothing and pollination of plants, people give little thought to the benefits of insects in their lives. This overview briefly describes significant recent advances in developing insect natural products as potential new medicinal drugs. This is an exciting and rapidly expanding new field since insects are hugely variable and have utilised an enormous range of natural products to survive environmental perturbations for 100s of millions of years. There is thus a treasure chest of untapped resources waiting to be discovered. Insects products, such as silk and honey, have already been utilised for thousands of years, and extracts of insects have been produced for use in Folk Medicine around the world, but only with the development of modern molecular and biochemical techniques has it become feasible to manipulate and bioengineer insect natural products into modern medicines. Utilising knowledge gleaned from Insect Folk Medicines, this review describes modern research into bioengineering honey and venom from bees, silk, cantharidin, antimicrobial peptides, and maggot secretions and anticoagulants from blood-sucking insects into medicines. Problems and solutions encountered in these endeavours are described and indicate that the future is bright for new insect derived pharmaceuticals treatments and medicines.

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Lucifensin, the long-sought antimicrobial factor of medicinal maggots of the blowfly Lucilia sericata

Cited by 133 publications

References 24 publications

Lucifensin, a Novel Insect Defensin of Medicinal Maggots: Synthesis and Structural Study

Lucifensin, a Novel Insect Defensin of Medicinal Maggots: Synthesis and Structural Study

Antimicrobial Peptides Expressed in Medicinal Maggots of the Blow Fly Lucilia sericata Show Combinatorial Activity against Bacteria

Recent Advances in Developing Insect Natural Products as Potential Modern Day Medicines

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