Diptericin

Diptericin
The blowfly Phormia terranova, in which Diptericin was first isolated
Identifiers
SymbolDiptericin, Dpt
InterProIPR040428

Diptericin is a 9 kDa antimicrobial peptide (AMP) of flies first isolated from the blowfly Phormia terranova.[1] 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.[2] Diptericin is an iconic readout of immune system activity in flies, used ubiquitously in studies of Drosophila immunity.[3] Diptericin is named after the insect order Diptera.

Structure and function

Diptericins are found throughout Diptera,[4] 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.[2][5] 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.[6] 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.[7] 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.[8]

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.[9] 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.[7][9][10][11]

Functions beyond antimicrobial activity

  • Diptericins can also have properties that reduce oxidative damage during the immune response.[12]
  • Suppression of the diptericin B and attacin C genes in Drosophila leads to increased Sindbis virus growth.[13]
  • Overexpression of diptericin and other antimicrobial peptides in the brains of flies leads to neurodegeneration.[14]
  • The Drosophila diptericin B gene is required for memory formation.[15]

References

  1. ↑ Dimarcq JL, Keppi E, Dunbar B, Lambert J, Reichhart JM, Hoffmann D, Rankine SM, Fothergill JE, Hoffmann JA (January 1988). "Insect immunity. Purification and characterization of a family of novel inducible antibacterial proteins from immunized larvae of the dipteran Phormia terranovae and complete amino-acid sequence of the predominant member, diptericin A". European Journal of Biochemistry. 171 (1–2): 17–22. doi:10.1111/j.1432-1033.1988.tb13752.x. PMID 3276515.
  2. 1 2 Cudic M, Bulet P, Hoffmann R, Craik DJ, Otvos L (December 1999). "Chemical synthesis, antibacterial activity and conformation of diptericin, an 82-mer peptide originally isolated from insects". European Journal of Biochemistry. 266 (2): 549–58. doi:10.1046/j.1432-1327.1999.00894.x. PMID 10561597.
  3. ↑ Lemaitre B, Hoffmann J (17 February 2019). "The host defense of Drosophila melanogaster". Annual Review of Immunology. 25: 697–743. doi:10.1146/annurev.immunol.25.022106.141615. PMID 17201680.
  4. ↑ Hanson MA, Hamilton PT, Perlman SJ (October 2016). "Immune genes and divergent antimicrobial peptides in flies of the subgenus Drosophila". BMC Evolutionary Biology. 16 (1): 228. doi:10.1186/s12862-016-0805-y. PMC 5078906. PMID 27776480.
  5. ↑ Hedengren, Marika; Borge, Karin; Hultmark, Dan (2000-12-20). "Expression and Evolution of the Drosophila Attacin/Diptericin Gene Family". Biochemical and Biophysical Research Communications. 279 (2): 574–581. doi:10.1006/bbrc.2000.3988. ISSN 0006-291X. PMID 11118328.
  6. ↑ Unckless RL, Howick VM, Lazzaro BP (January 2016). "Convergent Balancing Selection on an Antimicrobial Peptide in Drosophila". Current Biology. 26 (2): 257–262. doi:10.1016/j.cub.2015.11.063. PMC 4729654. PMID 26776733.
  7. 1 2 Unckless RL, Lazzaro BP (May 2016). "The potential for adaptive maintenance of diversity in insect antimicrobial peptides". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 371 (1695): 20150291. doi:10.1098/rstb.2015.0291. PMC 4874389. PMID 27160594.
  8. ↑ Hanson MA, Dostálová A, Ceroni C, Poidevin M, Kondo S, Lemaitre B (February 2019). "Synergy and remarkable specificity of antimicrobial peptides in vivo using a systematic knockout approach". eLife. 8. doi:10.7554/eLife.44341. PMC 6398976. PMID 30803481.
  9. 1 2 Hanson, Mark Austin; Lemaitre, Bruno; Unckless, Robert L. (2019). "Dynamic evolution of antimicrobial peptides underscores trade-offs between immunity and ecological fitness". Frontiers in Immunology. 10: 2620. doi:10.3389/fimmu.2019.02620. ISSN 1664-3224. PMC 6857651. PMID 31781114.
  10. ↑ Imler JL, Bulet P (17 February 2019). "Antimicrobial peptides in Drosophila: structures, activities and gene regulation". Chemical Immunology and Allergy. 86: 1–21. doi:10.1159/000086648. ISBN 978-3-8055-7862-2. PMID 15976485.
  11. ↑ Login FH, Balmand S, Vallier A, Vincent-Monégat C, Vigneron A, Weiss-Gayet M, Rochat D, Heddi A (October 2011). "Antimicrobial peptides keep insect endosymbionts under control". Science. 334 (6054): 362–5. Bibcode:2011Sci...334..362L. doi:10.1126/science.1209728. PMID 22021855. S2CID 23646646.
  12. ↑ Zhao HW, Zhou D, Haddad GG (February 2011). "Antimicrobial peptides increase tolerance to oxidant stress in Drosophila melanogaster". The Journal of Biological Chemistry. 286 (8): 6211–8. doi:10.1074/jbc.M110.181206. PMC 3057857. PMID 21148307.
  13. ↑ Huang Z, Kingsolver MB, Avadhanula V, Hardy RW (2013). "An Antiviral Role for Antimicrobial Peptides during the Arthropod Response to Alphavirus Replication". J Virol. 87 (8): 4272–80. doi:10.1128/JVI.03360-12. PMC 3624382. PMID 23365449.
  14. ↑ Cao Y, Chtarbanova S, Petersen AJ, Ganetzky B (May 2013). "Dnr1 mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain". Proceedings of the National Academy of Sciences of the United States of America. 110 (19): E1752-60. Bibcode:2013PNAS..110E1752C. doi:10.1073/pnas.1306220110. PMC 3651420. PMID 23613578.
  15. ↑ Barajas-Azpeleta R, Wu J, Gill J, Welte R, Seidel C, McKinney S, Dissel S, Si K (October 2018). "Antimicrobial peptides modulate long-term memory". PLOS Genetics. 14 (10): e1007440. doi:10.1371/journal.pgen.1007440. PMC 6224176. PMID 30312294.
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