Diptericin

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Diptericin
Pterraenovae.jpg
The blowfly Phormia terranova , in which Diptericin was first isolated
Identifiers
SymbolDiptericin, Dpt
InterPro IPR040428

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.

Contents

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] [8] 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. [9]

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. This convergent evolution is driven by presence of Acetobacter bacteria in fruit-feeding ecologies. [10] Absence of Acetobacter in other ecologies has led to subsequent loss of Diptericin B. [10] [11] Diptericin B loss is also convergent among lineages feeding on mushrooms or plants, including the mushroom-feeding fruit flies Leucophenga varia , Drosophila guttifera and Drosophila testacea , and plant-feeding Scaptomyza flies. [10]

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] [11] [12] [13]

Functions beyond antimicrobial activity

Related Research Articles

<i>Drosophila melanogaster</i> Species of fruit fly

Drosophila melanogaster is a species of fly in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly", or "banana fly". Starting with Charles W. Woodworth's 1901 proposal of the use of this species as a model organism, D. melanogaster continues to be widely used for biological research in genetics, physiology, microbial pathogenesis, and life history evolution. As of 2017, six Nobel Prizes have been awarded to drosophilists for their work using the insect.

<i>Providencia</i> (bacterium) Genus of bacteria

Providencia is genus of Gram-negative, motile bacteria of the family Morganellaceae. It was named after Providence, Rhode Island, where C. A. Stuart and colleagues studied these bacteria at Brown University.

<span class="mw-page-title-main">Jules A. Hoffmann</span> French biologist

Jules Alphonse Nicolas Hoffmann is a Luxembourg-born French biologist. During his youth, growing up in Luxembourg, he developed a strong interest in insects under the influence of his father, Jos Hoffmann. This eventually resulted in the younger Hoffmann's dedication to the field of biology using insects as model organisms. He currently holds a faculty position at the University of Strasbourg. He is a research director and member of the board of administrators of the National Center of Scientific Research (CNRS) in Strasbourg, France. He was elected to the positions of Vice-President (2005-2006) and President (2007-2008) of the French Academy of Sciences. Hoffmann and Bruce Beutler were jointly awarded a half share of the 2011 Nobel Prize in Physiology or Medicine for "their discoveries concerning the activation of innate immunity,". [More specifically, the work showing increased Drosomycin expression following activation of Toll pathway in microbial infection.]

<span class="mw-page-title-main">Arthropod defensin</span>

Arthropod defensins are a family defensin proteins found in mollusks, insects, and arachnids. These cysteine-rich antibacterial peptides are primarily active against Gram-positive bacteria and fungi in vitro. However Drosophila fruit flies mutant for the fly defensin were more susceptible to infection by the Gram-negative bacteria Providencia burhodogranariea, and resisted infection against Gram-positive bacteria like wild-type flies. It remains to be seen how in vitro activity relates to in vivo function. Mutants for the defensin-like antimicrobial peptide Drosomycin were more susceptible to fungi, validating a role for defensin-like peptides in anti-fungal defence.

Providencia rettgeri, is a Gram negative bacterium that is commonly found in both water and land environments. P. rettgeri is in the genus Providencia, along with Providencia stuartii, Providencia alcalifaciens, and Providencia rustigianii. P. rettgeri can be incubated at 37 °C in nutrient agar or nutrient broth. It was first discovered in 1904 after a waterfowl epidemic. Strains of the species have also been isolated from nematodes of the genus Heterorhabditis. Providencia rettgeri also found in marine environment.

The microbiota are the sum of all symbiotic microorganisms living on or in an organism. The fruit fly Drosophila melanogaster is a model organism and known as one of the most investigated organisms worldwide. The microbiota in flies is less complex than that found in humans. It still has an influence on the fitness of the fly, and it affects different life-history characteristics such as lifespan, resistance against pathogens (immunity) and metabolic processes (digestion). Considering the comprehensive toolkit available for research in Drosophila, analysis of its microbiome could enhance our understanding of similar processes in other types of host-microbiota interactions, including those involving humans. Microbiota plays key roles in the intestinal immune and metabolic responses via their fermentation product, acetate.

<span class="mw-page-title-main">Attacin</span>

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.

<span class="mw-page-title-main">Drosomycin</span>

Drosomycin is an antifungal peptide from Drosophila melanogaster and was the first antifungal peptide isolated from insects. 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 cecropins, diptericin, drosocin, metchnikowin and attacin, 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.

<i>Leucophenga varia</i> Species of insect

Leucophenga varia is a species of fly in the family Drosophilidae. It occurs in North America. Unlike other Drosophilidae, it feeds on mushrooms, which has impacted the evolution of the Diptericin gene of its innate immune system.

<i>Drosophila neotestacea</i> Species of fly

Drosophila neotestacea is a member of the testacea species group of Drosophila. Testacea species are specialist fruit flies that breed on the fruiting bodies of mushrooms. These flies will choose to breed on psychoactive mushrooms such as the Fly Agaric Amanita muscaria. Drosophila neotestacea can be found in temperate regions of North America, ranging from the north eastern United States to western Canada.

<i>Drosophila testacea</i> Species of fly

Drosophila testacea is a member of the testacea species group of Drosophila. Testacea species are specialist fruit flies that breed on the fruiting bodies of mushrooms. Drosophila testacea can be found in temperate regions of Europe, extending to east Asia. Drosophila testacea and Drosophila orientacea can produce viable hybrids, though they are separated by geography and behavioural barriers. Drosophila testacea females will also readily mate with Drosophila neotestacea males, but viable hybrids are never produced. This hybrid inviability ) may be due to selfish X chromosomes and co-evolved suppressors. Alternately, differences in sex pheromone reception could underlie female readiness and male willingness to copulate.

Spiroplasma poulsonii are bacteria of the genus Spiroplasma that are commonly endosymbionts of flies. These bacteria live in the hemolymph of the flies, where they can act as reproductive manipulators or defensive symbionts.

<span class="mw-page-title-main">Drosocin</span> Antimicrobial peptide

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 signalling pathway in the fly.

<span class="mw-page-title-main">Metchnikowin</span> Antimicrobial peptide

Metchnikowin is a 26-residue antimicrobial peptide of the fruit fly Drosophila melanogaster that displays both antibacterial and antifungal properties. This peptide is expressed strongly in the Drosophila fat body, but is also expressed at surface epithelia in the trachea and gut. This is regulated by the NF-κB signalling pathways Toll and Imd. Metchnikowin is named after Russian immunologist Élie Metchnikoff, one of the founders of modern immunology.

<i>Drosophila quinaria</i> species group Species group of the subgenus Drosophila

The Drosophila quinaria species group is a speciose lineage of mushroom-feeding flies studied for their specialist ecology, their parasites, population genetics, and the evolution of immune systems. Quinaria species are part of the Drosophila subgenus.

<i>Drosophila innubila</i> Species of fly

Drosophila innubila is a species of vinegar fly restricted to high-elevation woodlands in the mountains of the southern USA and Mexico, which it likely colonized during the last glacial period. Drosophila innubila is a kind of mushroom-breeding Drosophila, and member of the Drosophila quinaria species group. Drosophila innubila is best known for its association with a strain of male-killing Wolbachia bacteria. These bacteria are parasitic, as they drain resources from the host and cause half the infected female's eggs to abort. However Wolbachia may offer benefits to the fly's fitness in certain circumstances. The D. innubila genome was sequenced in 2019.

<span class="mw-page-title-main">Imd pathway</span> Immune signaling pathway of insects

The Imd pathway is a broadly-conserved NF-κB immune signalling pathway of insects and some arthropods that regulates a potent antibacterial defence response. The pathway is named after the discovery of a mutation causing severe immune deficiency. The Imd pathway was first discovered in 1995 using Drosophila fruit flies by Bruno Lemaitre and colleagues, who also later discovered that the Drosophila Toll gene regulated defence against Gram-positive bacteria and fungi. Together the Toll and Imd pathways have formed a paradigm of insect immune signalling; as of September 2, 2019, these two landmark discovery papers have been cited collectively over 5000 times since publication on Google Scholar.

<span class="mw-page-title-main">Morganellaceae</span> Family of bacteria

The Morganellaceae are a family of Gram-negative bacteria that include some important human pathogens formerly classified as Enterobacteriaceae. This family is a member of the order Enterobacterales in the class Gammaproteobacteria of the phylum Pseudomonadota. Genera in this family include the type genus Morganella, along with Arsenophonus, Cosenzaea, Moellerella, Photorhabdus, Proteus, Providencia and Xenorhabdus.

Baramicin (Bara) is an antimicrobial peptide gene of the fruit fly Drosophila melanogaster. Baramicin is a prominent element of the fly immune response: of the most abundant immune peptides detected in the fly hemolymph, the BaraA gene is responsible for 9 of the 24 peptides first described for their high concentrations after systemic infection.

<span class="mw-page-title-main">Bomanin</span> Antimicrobial peptide-like immune gene of fruit flies

The Bomanin gene family encodes a group of immune peptides that are essential for Drosophila fruit fly defence against infection by many pathogens.

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