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.
Highlights
Over the course of their evolution, insects have developed an amazing resistance to bacterial infection, resulting in exceptional adaptation to a variety of natural environments often considered rather unsanitary by human standards
Insects respond to bacterial challenge or injury by rapid production of antimicrobial peptides (AMPs) that have a broad spectrum of activity against Gram-positive and
Lucifensin are the key antimicrobial peptides involved in the defence system of the blowfly larvae Lucilia sericata and Lucilia cuprina. These fly larvae are routinely used at hospitals worldwide during a procedure known as maggot debridement therapy (MDT) [12,13]
Summary
Over the course of their evolution, insects have developed an amazing resistance to bacterial infection, resulting in exceptional adaptation to a variety of natural environments often considered rather unsanitary by human standards. AMPs are synthesised in the fat body (the equivalent of the mammalian liver), epithelial cells, and in the certain cells of the haemolymph (the equivalent of mammalian blood) and spread by the haemolymph over the entire body to fight infection [2] The majority of these peptides belong to the class of cationic AMPs of molecular masses below 5 kDa [3]. The frequent occurrence of positively charged amino acid residues (Arg, Lys) in their molecules allows them to interact with the anionic phospholipids of bacterial membranes. This is followed by integration of the peptides into the lipid bilayer and disruption of the membrane structure via different modes that lead to leakage of cytoplasmic components and cell death [4,5,6]. These fly larvae are routinely used at hospitals worldwide during a procedure known as maggot debridement therapy (MDT) [12,13]
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