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 includes a proline-rich domain with similarities to the AMPs drosocin, pyrrhocoricin, and abaecin, and a glycine-rich domain with similarity to attacin. Diptericin is an iconic readout of immune system activity in flies, used ubiquitously in studies of ''Drosophila'' immunity. Diptericin is named after the insect order Diptera.

Structure and function

Diptericins are found throughout Diptera, but are most extensively characterized in ''Drosophila'' fruit flies. The mature structures of diptericins are unknown, though previous efforts to synthesize Diptericin have suggested Diptericin in ''Protophormia terraenovae'' is one linear peptide. Yet ''Drosophila melanogaster's'' Diptericin B peptide is likely cleaved into two separate peptides. Synthesis of Diptericin in vitro found activity of the full-length peptide, but independently synthesizing the two peptides and mixing them does not recapitulate Diptericin activity. Diptericin A activity is strongly tied to residues in the glycine-rich domain.

Diptericin as a model for understanding the specificity of host-pathogen interactions

A polymorphism at a single residue in the diptericin glycine-rich domain drastically affects its activity against the Gram-negative bacterium ''Providencia rettgeri''. Flies with a ''Diptericin A'' gene encoding a serine allele survive infection significantly more than flies with an arginine allele. It is unclear how frequently such polymorphisms may dictate host-pathogen interactions, but there is evidence of widespread balancing selection that diptericin is not the only AMP with such polymorphisms. This close association between diptericin and ''P. rettgeri'' is further supported by genetic approaches that show that diptericin is the only antimicrobial peptide of the ''Drosophila'' immune response that affects resistance to ''P. rettgeri''.

The fruit fly Diptericin gene ''"Diptericin B"'' has a unique structure that has been derived independently in both Tephritidae and ''Drosophila'' fruit flies. This represents convergent evolution of an antimicrobial peptide towards a common structure in two separate fruit-feeding lineages. More surprisingly, sub-lineages of both Tephritidae and ''Drosophila'' that have specialized on non-fruit food sources have subsequently lost Diptericin B. In the mushroom-feeding fruit flies ''Drosophila guttifera'' and ''Drosophila testacea'', this loss appears to have happened independently, as the mutations in these species' ''Diptericin B'' genes are different. This repeated loss of Diptericin B in fruit flies that have diverged to feed on non-fruit foods suggests Diptericin B is attuned to a fruit-feeding lifestyle, but unimportant and possibly even deleterious in non-fruit ecologies.

These observations are part of a growing body of evidence that antimicrobial peptides can have intimate associations with microbes, and perhaps host ecology, in contrast to the previous philosophy that these peptides act in generalist and redundant fashions.

Functions beyond antimicrobial activity

*Diptericins can also have properties that reduce oxidative damage during the immune response.
*Suppression of the ''diptericin B'' and ''attacin C'' genes in ''Drosophila'' leads to increased Sindbis virus growth.''
*Overexpression of diptericin and other antimicrobial peptides in the brains of flies leads to neurodegeneration.
*The ''Drosophila'' diptericin B gene is required for memory formation.

References

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Drosophila
Insect immunity
Antimicrobial peptides