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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Wolbachia enhances the survival of Drosophila infected with fungal pathogens

BMC Biology, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 11, 2025

Wolbachia bacteria of arthropods are at the forefront basic and translational research on multipartite host-symbiont-pathogen interactions. These vertically transmitted microbes most widespread endosymbionts planet due to factors including host reproductive manipulation fitness benefits. Importantly, some strains can inhibit viral pathogenesis within between arthropod hosts. Mosquitoes carrying wMel strain Drosophila melanogaster have a greatly reduced capacity spread viruses like dengue Zika humans. While significant efforts focused viruses, relatively little attention has been given Wolbachia-fungal interactions despite ubiquity fungal entomopathogens in nature. Here, we demonstrate that increase longevity their hosts when challenged with spectrum yeast filamentous pathogens. We find this pattern vary based genotype, sex, species. Further, correlates higher fertility pathogen titers during initial infection, indicating benefit. Finally, RNA sequencing results show altered expression many immune stress response genes context suggesting immunity may be involved mechanism. This study demonstrates Wolbachia's protective role diverse determines phenotype is broad, but several variables influence both presence strength phenotype. It also critical step forward understanding how symbionts protect from variety

Language: Английский

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IMD-mediated innate immune priming increases Drosophila survival and reduces pathogen transmission

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(6), P. e1012308 - e1012308

Published: June 10, 2024

Invertebrates lack the immune machinery underlying vertebrate-like acquired immunity. However, in many insects past infection by same pathogen can ‘prime’ response, resulting improved survival upon reinfection. Here, we investigated mechanistic basis and epidemiological consequences of innate priming fruit fly Drosophila melanogaster when infected with gram-negative bacterial Providencia rettgeri . We find that response to P is a long-lasting sexually dimorphic response. further explore it has potential curtail transmission reducing shedding spread. The enhanced individuals previously exposed non-lethal inoculum coincided transient decrease loads, provide strong evidence effect requires IMD-responsive antimicrobial-peptide Diptericin-B fat body. Further, show while Diptericin B main effector clearance, not sufficient for priming, which regulation IMD peptidoglycan recognition proteins. This work underscores plasticity complexity invertebrate responses infection, providing novel experimental effects on population-level outcomes.

Language: Английский

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Mapping the functional form of the trade-off between infection resistance and reproductive fitness under dysregulated immune signaling

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(2), P. e1012049 - e1012049

Published: Feb. 26, 2024

Immune responses benefit organismal fitness by clearing parasites but also exact costs associated with immunopathology and energetic investment. Hosts manage these tightly regulating the induction of immune signaling to curtail excessive restore homeostasis. Despite theoretical importance turning off response mitigate costs, experimentally connecting variation in negative regulation remains a frontier evolutionary immunology. In this study, we used dose-response approach manipulate RNAi-mediated knockdown efficiency cactus (IκBα), central regulator Toll pathway signal transduction flour beetles (Tribolium castaneum). By titrating activity across four distinct levels, derived shape relationship between investment traits host fitness, including infection susceptibility, lifespan, fecundity, body mass, gut Cactus knock-down increased overall magnitude inducible delayed their resolution dsRNA dose-dependent manner, promoting survival resistance following bacterial infection. However, benefits were counterbalanced integrity. Our results allowed us move beyond qualitative identification trade-off actually derive its functional form. This paves way quantitatively compare evolution impact regulatory elements on life-history trade-offs filling crucial gap our conceptual models network maintenance natural systems.

Language: Английский

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Non-Immune Functions of Innate Immunity Acting on Physiological Processes: Insights from Drosophila

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1087 - 1087

Published: Jan. 27, 2025

As the first line of host immune defense, innate immunity plays a key role in warding off foreign pathogens and damage. Drosophila melanogaster, as classical model animal for more than 100 years, is an important research studying immunity. In recent scientists have made remarkable progress recognition mechanisms immunity, effector molecules, modes their response at cellular tissue levels. However, interaction between other physiological functions remains relatively novel has yet to be systematically explored. Here, we briefly discuss link system regulation, from several representative perspectives such sleep, insulin, brain function. Then, using model, provide overview specifically summarize on regulation physiology by covering lipid metabolism, development, neurodegenerative diseases, memory, feeding, lifespan, movement, antioxidation. This review provides valuable into how influences processes, providing deeper understanding complex roles underlying

Language: Английский

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The role of MKI67 in the regulation of 60S pre-ribosome nucleolar export, transcripts, energy supply, and apoptosis

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 16, 2025

MKI67 (Ki67) is expressed exclusively in proliferating cells human tissues, rendering it as a valuable diagnostic marker for cancer. However, the function of this protein remains unclear. In study, we present findings on regulatory functions conjunction with its partner proteins GNL2 and MDN1, which are involved pre-ribosome processing, well absence. HEK293T cells, binds contiguously to chromatin localizing most densely nucleolar periphery regulate 60S export. On other hand, RNA-seq analysis reveals that these three can independently many target transcripts, but they often share their yet them at different expression levels. MDN1 depletion strongly downregulates RNA gene transcripts ribosome biogenesis splicing. contrast, upregulates protein-coding genes, including synapse-specific mitosis-related HEK7. Furthermore, coordinately up-or down-regulates levels several pathways, thereby enabling MKI67-depleted adapt less active metabolic states. The underlying mechanism by appears involve attenuation transcript cooperation mRNA degradation systems, evidenced HEK7 UNC13A translations. conclusion, results indicate contributes proliferation via export particles high energy supply. Conversely, absence leads senescent differentiated conditions.

Language: Английский

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Evolution of resistance and disease tolerance mechanisms to oral bacterial infection in Drosophila melanogaster

Open Biology, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

Pathogens exert strong selection on hosts that evolve and deploy different defensive strategies, namely minimizing pathogen exposure (avoidance), directly promoting elimination (resistance) and/or managing the deleterious effects of illness (disease tolerance). However, how host response partitions across these processes has not been tested in a single host–pathogen system, let alone context known adaptive trajectories resulting from experimental evolution. Here, we compare Drosophila melanogaster population adapted to oral infection with its natural Pseudomonas entomophila (BactOral), control find no evidence for behavioural changes but measurable differences both resistance disease tolerance. In BactOral, were detected bacterial intake or defecation, nor gut cell renewal. relative decrease loads correlates an increase gut-specific anti-microbial peptide production, pointing strengthening resistance. Additionally, posit tolerance also contributes BactOral through tighter self- pathogen-derived damage caused by bacteria exposure. This study reveals genetically complex mechanistically multi-layered response, possibly reflecting structure adaptation populations.

Language: Английский

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Variation in mitochondrial DNA affects locomotor activity and sleep in Drosophila melanogaster

Heredity, Journal Year: 2022, Volume and Issue: 129(4), P. 225 - 232

Published: June 28, 2022

Abstract Mitochondria are organelles that produce cellular energy in the form of ATP through oxidative phosphorylation, and this primary function is conserved among many taxa. Locomotion a trait highly reliant on metabolic expected to be greatly affected by disruptions mitochondrial performance. To end, we aimed examine how activity sleep vary between Drosophila melanogaster strains with different geographic origins, these patterns DNA (mtDNA) variation, breaking up co-evolved mito-nuclear gene combinations affect studied traits. Our results demonstrate from locations differ activity, females generally more active than males. By comparing mtDNA variants introgressed onto common nuclear background cytoplasmic hybrid (cybrid) strains, were able quantify among-line variance attributable DNA, establish variation affects both sleep, sex-specific manner. Altogether our study highlights important role genome plays organismal physiology behaviour.

Language: Английский

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Duox and Jak/Stat signalling influence disease tolerance in Drosophila during Pseudomonas entomophila infection

Developmental & Comparative Immunology, Journal Year: 2023, Volume and Issue: 147, P. 104756 - 104756

Published: June 10, 2023

Disease tolerance describes an infected host's ability to maintain health independently of the clear microbe loads. The Jak/Stat pathway plays a pivotal role in humoral innate immunity by detecting tissue damage and triggering cellular renewal, making it candidate mechanism. Here, we find that Drosophila melanogaster with Pseudomonas entomophila disrupting ROS-producing dual oxidase (duox) or negative regulator Socs36E, render male flies less tolerant. Another Jak/Stat, G9a - which has previously been associated variable viral infections did not affect rate mortality increasing loads compared functional G9a, suggesting does bacterial infection as infection. Our findings highlight ROS production signalling influence tolerate sex-specifically may therefore contribute sexually dimorphic outcomes Drosophila.

Language: Английский

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Wolbachiaenhances the survival ofDrosophilainfected with fungal pathogens

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 30, 2023

Abstract Wolbachia bacteria of arthropods are at the forefront basic and translational research on multipartite host-symbiont-pathogen interactions. These microbes vertically inherited from mother to offspring via cytoplasm. They most widespread endosymbionts planet due their infamous ability manipulate reproduction hosts spread themselves in a population, provide variety fitness benefits hosts. Importantly, some strains can inhibit viral pathogenesis within between arthropod Mosquitoes carrying w Mel strain Drosophila melanogaster have greatly reduced capacity viruses like dengue Zika humans. Therefore, basis several global vector control initiatives. While significant efforts focused viruses, relatively little attention has been given -fungal interactions despite ubiquity fungal entomopathogens nature. Here, we demonstrate that increase longevity when challenged with spectrum yeast filamentous pathogens. We find this pattern vary based host genotype, sex, species. Further, correlates higher fertility pathogen titers during initial infection, indicating benefit. This study demonstrates ’s role diverse determines phenotype is broad, but variables influence both presence strength phenotype. results enhance our knowledge strategies uses likely contribute such high symbiont prevalence. Importance initiatives fight arthropod-borne viruses. Despite great success using , same widely used antiviral initiatives, also flies systemically infected panel The partially increases reduces early represents major step forward since its blocking abilities now be extended broad diversity another branch microbial life. discovery may inform potential applications areas including biocontrol agriculture.

Language: Английский

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