Lucifensins, the Insect Defensins of Biomedical Importance: The Story behind Maggot Therapy

Abstract

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.

In vitro antimicrobial activity of maggot excretions/secretions of Sarcophaga (Liopygia) argyrostoma (Robineau-Desvoidy)

“…S. peregrine sapecin possesses an N-terminal flexible loop, a central α-helix and a C-terminal anti-parallel β-sheet (Hanzawa et al, 1990). L. sericata defensin (lucifensin) differs from sapecin by five amino acid residues (Čeřovský and Bém, 2014). Sarcotoxin 1A, a cecropin antimicrobial peptide from S. peregrine, was found to be primarily active against Gram-negative bacteria but shows moderate activity towards Gram-positive bacteria (Natori, 2010), which agrees with our results.…”

“…Sapecin, a medium-sized cationic peptide belongs to the dipteran defensins, was isolated from the culture medium of the embryonic cell line of S. peregrine (Matsuyama and Natori, 1988). Defensins are 4-6 kDa cyclic peptides and are the most widespread insect's AMPs (Čeřovský and Bém, 2014). S. peregrine sapecin possesses an N-terminal flexible loop, a central α-helix and a C-terminal anti-parallel β-sheet (Hanzawa et al, 1990).…”

A Family of CSαβ Defensins and Defensin-Like Peptides from the Migratory Locust, Locusta migratoria, and Their Expression Dynamics during Mycosis and Nosemosis

“…The conserved dibasic cleavage sites (-KR- and -RR-) have been found in many defensin sequences identified from different insect orders, including Anoplura, Heteroptera, Diptera, and Coleoptera [3, 4]. The consensus motifs of LmDEFs is consistent with the spacing pattern of insect defensins (C-X 5–16 -C-X 3 -C-X 9–11 -C-X 4–7 -C-X 1 -C) [57]. The strategy used for transcriptome analysis and mining was very effective, with the identification of four new defensins.…”

Host defense antimicrobial peptides as antibiotics: design and application strategies

“…Importantly, in vivo efficacy of this approach has been demonstrated in a rabbit model for Shigellosis. In the same vein, the maggot therapy is likely related to the expression and secretion of AMPs such as lucifensin into infected wounds by fly larvae that promote healing [69]. …”