Drosomycin is an antifungal

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Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (the taxonomic order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the " vinegar fly" or "pomace fly". Starting with ...

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insect Insects (from Latin ') are pancrustacean hexapod invertebrates of the class Insecta. They are the largest group within the arthropod phylum. Insects have a chitinous exoskeleton, a three-part body ( head, thorax and abdomen), three ...

s. Drosomycin is induced by infection by the Toll signalling pathway, while expression in surface epithelia like the respiratory tract is instead controlled by the immune deficiency pathway (Imd). This means that drosomycin, alongside other antimicrobial peptides (AMPs) such as

cecropin Cecropins are antimicrobial peptides. They were first isolated from the hemolymph of ''Hyalophora cecropia'', whence the term cecropin was derived. Cecropins lyse bacterial cell membranes; they also inhibit proline uptake and cause leaky membrane ...

diptericin Diptericin is a 9 kDa antimicrobial peptide (AMP) of flies first isolated from the blowfly '' Phormia terranova''. It is primarily active against Gram-negative bacteria, disrupting bacterial membrane integrity. The structure of this protein incl ...

drosocin Drosocin is a 19-residue long antimicrobial peptide (AMP) of flies first isolated in the fruit fly ''Drosophila melanogaster'', and later shown to be conserved throughout the genus ''Drosophila''. Drosocin is regulated by the NF-κB Imd signalli ...

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attacin Attacin is a glycine-rich protein of about 20 kDa belonging to the group of antimicrobial peptides (AMP). It is active against Gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gr ...

, serves as a first line defence upon septic injury. However drosomycin is also expressed constitutively to a lesser extent in different tissues and throughout development.

Structure

Drosomycin is a 44-residue defensin-like peptide containing four disulfide bridges. These bridges stabilize a structure involving one α-helix and three β-sheets. Owing to these four disulfide bridges, drosomycin is resistant to degradation and the action of proteases. The cysteine stabilized αβ motif of drosomycin is also found in ''Drosophila'' defensin, and some plant defensins. Drosomycin has greater sequence similarity with these plant defensins (up to 40%), than with other insect defensins. The structure was discovered in 1997 by Landon and his colleagues The αβ motif of drosomycin is also found in a scorpion neurotoxin, and drosomycin potentiates the action of this neurotoxin on nerve excitation.

Drosomycin multigene family

At the nucleotide level, drosomycin is a 387 bp-long gene (''Drs'') which lies on Muller element 3L, very near six other drosomycin-like (Drsl) genes. These various drosomycins are referred to as the drosomycin multigene family. However, only drosomycin itself is part of the systemic immune response, while the other genes are regulated in different fashions. The antimicrobial activity of these various drosomycin-like peptides also differs. In 2015 Gao and Zhu found that in some ''Drosophila'' species (''D. takahashii'') some of these genes have been duplicated and this Drosophila has 11 genes in the drosomycin multigene family in total.

Function

It seems that drosomycin has about three major functions on fungi, the first is partial lysis of hyphae, the second is inhibition of spore germination (in higher concentrations of drosomycin), and the last is delaying of hypha growth, which leads to hyphae branching (at lower concentrations of drosomycin). The exact mechanism of function to fungi still has to be clarified. In 2019, Hanson and colleagues{{cite journal , vauthors = Hanson MA, Dostálová A, Ceroni C, Poidevin M, Kondo S, Lemaitre B , title = Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach , journal = eLife , volume = 8 , date = February 2019 , pmid = 30803481 , pmc = 6398976 , doi = 10.7554/eLife.44341 , doi-access = free generated the first drosomycin mutant, finding that indeed flies lacking drosomycin were more susceptible to fungal infection.

References

Peptides Antifungals Defensins