Unraveling the Role of Antimicrobial Peptides in Insects

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5753 - 5753

Published: March 17, 2023

Antimicrobial peptides (AMPs) are short, mainly positively charged, amphipathic molecules. AMPs important effectors of the immune response in insects with a broad spectrum antibacterial, antifungal, and antiparasitic activity. In addition to these well-known roles, exhibit many other, often unobvious, functions host. They support elimination viral infections. participate regulation brain-controlled processes, e.g., sleep non-associative learning. By influencing neuronal health, communication, activity, they can affect functioning insect nervous system. Expansion AMP repertoire loss their specificity is connected aging process lifespan insects. Moreover, take part maintaining gut homeostasis, regulating number endosymbionts as well reducing foreign microbiota. turn, presence venom prevents spread infection social insects, where prey may be source pathogens.

Language: Английский

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Ecology-relevant bacteria drive the evolution of host antimicrobial peptides in Drosophila

Science, Journal Year: 2023, Volume and Issue: 381(6655)

Published: July 20, 2023

Antimicrobial peptides are host-encoded immune effectors that combat pathogens and shape the microbiome in plants animals. However, little is known about how host antimicrobial peptide repertoire adapted to its microbiome. Here, we characterized function evolution of Diptericin family Diptera. Using mutations affecting two Diptericins ( Dpt ) Drosophila melanogaster , reveal specific role DptA for pathogen Providencia rettgeri DptB gut mutualist Acetobacter . The presence DptA- or DptB- like genes across Diptera correlates with their environment. Moreover, sequences predict resistance against infection by these bacteria genus Our study explains evolutionary logic behind bursts rapid an reveals adapts changing microbial environments.

Language: Английский

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The conceptual foundations of innate immunity: Taking stock 30 years later

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 613 - 631

Published: April 1, 2024

SummaryWhile largely neglected over decades during which adaptive immunity captured most of the attention, innate immune mechanisms have now become central to our understanding immunology. Innate provides first barrier infection in vertebrates, and it is sole mechanism host defense invertebrates plants. also plays a critical role maintaining homeostasis, shaping microbiota, disease contexts such as cancer, neurodegeneration, metabolic syndromes, aging. The emergence field has led an expanded view system, no longer restricted vertebrates instead concerns all metazoans, plants, even prokaryotes. study given rise new concepts language. Here, we review history definition core immunity, discussing their value fruitfulness long run.

Language: Английский

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Suppression of Drosophila antifungal immunity by a parasite effector via blocking GNBP3 and GNBP-like 3, the dual receptors for β-glucans

Cell Reports, Journal Year: 2024, Volume and Issue: 43(1), P. 113642 - 113642

Published: Jan. 1, 2024

The tactics used by animal pathogens to combat host immunity are largely unclear. Here, we report the depiction of virulence-required effector Tge1 deployed entomopathogen Metarhizium robertsii suppress Drosophila antifungal immunity. can target both GNBP3 and GNBP-like 3 (GL3), latter bind β-glucans like GNBP3, whereas glucan binding receptors be attenuated Tge1. As opposed surveillance GL3 is inducible in depending on Toll pathway via a positive feedback loop mechanism. Losses genes result deregulations protease cascade, Spätzle maturation, antimicrobial gene expressions upon fungal challenges. Fly survival assays confirm that plays more essential role than combating infections. In addition evidencing gene-for-gene interactions between fungi insects, our data advance insights into

Language: Английский

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When the microbiome shapes the host: immune evolution implications for infectious disease

Philosophical Transactions of the Royal Society B Biological Sciences, Journal Year: 2024, Volume and Issue: 379(1901)

Published: March 18, 2024

The microbiome includes both ‘mutualist’ and ‘pathogen’ microbes, regulated by the same innate immune architecture. A major question has therefore been: how do hosts prevent pathogenic infections while maintaining beneficial microbes? One idea suggests can selectively activate immunity upon infection, but not mutualist colonization. Another posits that attack pathogens, mutualists. Here I review evolutionary principles of microbe recognition activation, reflect on newly observed effector–microbe specificity perhaps supporting latter idea. Recent work in Drosophila found a surprising importance for single antimicrobial peptides combatting specific ecologically relevant microbes. developing picture these effectors have evolved this purpose. Other defence responses like reactive oxygen species bursts also be uniquely effective against Signals other model systems including nematodes, Hydra , oysters, mammals, suggest may fundamental principle host–pathogen interactions. propose stems from weaknesses microbes themselves: if intrinsic weaknesses, evolve exploit those weaknesses. define host–microbe relationship as ‘the Achilles evolution’. Incorporating view helps interpret why some interactions develop coevolutionary framework (e.g. Red Queen dynamics), or one-sided response. This clarification should valuable to better understand behind host susceptibilities infectious diseases. article is part theme issue ‘Sculpting microbiome: factors determine respond microbial colonization’.

Language: Английский

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A single amino acid polymorphism in natural Metchnikowin alleles of Drosophila results in systemic immunity and life history tradeoffs

PLoS Genetics, Journal Year: 2024, Volume and Issue: 20(3), P. e1011155 - e1011155

Published: March 11, 2024

Antimicrobial peptides (AMPs) are at the interface of interactions between hosts and microbes therefore expected to be rapidly evolving in a coevolutionary arms race with pathogens. In contrast, previous work demonstrated that insect AMPs tend evolve more slowly than genome average. Metchikowin (Mtk) is Drosophila AMP has single amino acid residue segregates as either proline (P) or arginine (R) populations four different species, some which diverged 10 million years ago. These results suggest there distinct functional importance each allele. The most likely hypotheses driven by two main questions: does allele have efficacy against specific pathogens (specificity hypothesis)? Or, one potent antimicrobial, but host fitness cost (autoimmune To assess their differences, we created D . melanogaster lines P allele, R Mtk null mutation using CRISPR/Cas9 editing performed series life history infection assays them. males, testing systemic immune responses repertoire bacteria fungi performs well better alleles infections. Females show contrast not contributing survival outperforming addition, measurements traits demonstrate costly absence for both sexes. consistent specificity hypothesis (either can perform certain depending on context), autoimmune (the generally antimicrobial carries cost). provide strong vivo evidence differential without sex-based differences may adaptive mechanisms maintaining gene polymorphisms expectations rapid evolution. Therefore, complex interplay forces including pathogen species sex lead balancing selection genotypes. Strikingly, this act even polymorphism an AMP.

Language: Английский

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A Toll pathway effector protects Drosophila specifically from distinct toxins secreted by a fungus or a bacterium

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(12)

Published: March 14, 2023

The Drosophila systemic immune response against many Gram-positive bacteria and fungi is mediated by the Toll pathway. How Toll-regulated effectors actually fulfill this role remains poorly understood as known antimicrobial peptide (AMP) genes are active only filamentous not or yeasts. Besides AMPs, two families of peptides secreted in to infectious stimuli that activate pathway have been identified, namely Bomanins derived from a polyprotein precursor Baramicin A (BaraA). Unexpectedly, deletion cluster 10 phenocopies mutant phenotype susceptibility infections. Here, we demonstrate BaraA required specifically host defense Enterococcus faecalis entomopathogenic fungus Metarhizium robertsii , albeit fungal burden altered mutants. protects fly action distinct toxins these pathogens, respectively, Enterocin V Destruxin A. injection leads rapid paralysis flies, whether wild type (WT) mutant. However, larger fraction wild-type than flies recovers within 5 h. BaraAs' function protecting deleterious glial cells, highlighting resilience for nervous system microbial virulence factors. Thus, complement current paradigm, innate immunity can cope effectively with effects pathogens through secretion dedicated peptides, independently xenobiotics detoxification pathways.

Language: Английский

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The Toll pathway mediates Drosophila resilience to Aspergillus mycotoxins through specific Bomanins

EMBO Reports, Journal Year: 2022, Volume and Issue: 24(1)

Published: Nov. 2, 2022

Host defense against infections encompasses both resistance, which targets microorganisms for neutralization or elimination, and resilience/disease tolerance, allows the host to withstand/tolerate pathogens repair damages. In Drosophila, Toll signaling pathway is thought mediate resistance fungal by regulating secretion of antimicrobial peptides, potentially including Bomanins. We find that Aspergillus fumigatus kills Drosophila mutants without invasion because its dissemination blocked melanization, suggesting a role in distinct from resistance. report affecting 55C Bomanin locus are susceptible injection two mycotoxins, restrictocin verruculogen. The vulnerability deletion these mycotoxins rescued overexpression Bomanins specific each challenge. Mechanistically, flies BomS6 expressed nervous system exhibit an enhanced recovery tremors induced injected verruculogen display improved survival. Thus, innate immunity also protects action microbial toxins through secreted peptides thereby increases resilience infection.

Language: Английский

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MprF-mediated immune evasion is necessary for Lactiplantibacillus plantarum resilience in the Drosophila gut during inflammation

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(8), P. e1012462 - e1012462

Published: Aug. 19, 2024

Multiple peptide resistance factor (MprF) confers to cationic antimicrobial peptides (AMPs) in several pathogens, thereby enabling evasion of the host immune response. The role MprF commensals remains, however, uncharacterized. To close this knowledge gap, we used a common gut commensal animals, Lactiplantibacillus plantarum , and its natural host, fruit fly Drosophila melanogaster as an experimental model investigate commensal-host interactions. L . ΔmprF mutant that generated exhibited deficiency synthesis lysyl-phosphatidylglycerol (Lys-PG), resulting increased negative cell surface charge susceptibility AMPs. Susceptibility AMPs had no effect on mutant’s ability colonize guts uninfected flies. However, observed significantly reduced abundance after infection-induced inflammation wild-type flies but not lacking Additionally, found compared induces stronger intestinal response due release immunostimulatory peptidoglycan fragments, indicating important promoting tolerance commensals. Our further analysis suggests MprF-mediated lipoteichoic acid modifications are involved immunomodulation. Overall, our results demonstrate MprF, besides well-characterized pathogen virulence, is also resilience factor.

Language: Английский

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A specific innate immune response silences the virulence of Pseudomonas aeruginosa in a latent infection model in the Drosophila melanogaster host

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(6), P. e1012252 - e1012252

Published: June 4, 2024

Microbial pathogenicity often depends on the route of infection. For instance, P . aeruginosa or S marcescens cause acute systemic infections when low numbers bacteria are injected into D melanogaster flies whereas succumb much slower to continuous ingestion these pathogens, even though both manage escape from gut compartment and reach hemocoel. Here, we have developed a latent infection model by feeding for short period. The stably colonize internal tissues yet hardly any damage since latently-infected live almost as long noninfected control flies. apparently dormant display particular characteristics in terms bacterial colony morphology, composition outer cell wall, motility. virulence can however be reactivated upon wounding host. We show that melanization but not cellular humoral response is predominant host defense establishes latency may coerce state. In addition, lasting activation responses provides degree protection against secondary fungal Latent an ingested pathogen protects variety homologous heterologous infectious challenges, situation previously described endosymbiotic Wolbachia bacteria, guard viral infections.

Language: Английский

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