Antimicrobial peptides do not directly contribute to aging in Drosophila, but improve lifespan by preventing dysbiosis

Disease Models & Mechanisms, Journal Year: 2023, Volume and Issue: 16(4)

Published: Feb. 27, 2023

Antimicrobial peptides (AMPs) are innate immune effectors first studied for their role in host defence. Recent studies have implicated these the clearance of aberrant cells and neurodegenerative syndromes. In Drosophila, many AMPs produced downstream Toll Imd NF-κB pathways upon infection. Upon aging, upregulated, drawing attention to molecules as possible causes age-associated inflammatory diseases. However, functional overexpressing or silencing genes been inconclusive. Using an isogenic set AMP gene deletions, we investigated net impact on aging. Overall, found no major effect individual lifespan, with exception Defensin. ΔAMP14 flies lacking seven families displayed reduced lifespan. Increased bacterial load food aged suggested that lifespan reduction was due microbiome dysbiosis, consistent a previous study. Moreover, germ-free conditions extended flies. our results did not point overt Instead, collectively by preventing dysbiosis during

Language: Английский

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Resistance to host antimicrobial peptides mediates resilience of gut commensals during infection and aging in Drosophila

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(36)

Published: Aug. 28, 2023

Resilience to short-term perturbations, like inflammation, is a fundamental feature of microbiota, yet the underlying mechanisms microbiota resilience are incompletely understood. Here, we show that Lactiplantibacillus plantarum , major Drosophila commensal, stably colonizes fruit fly gut during infection and resistant antimicrobial peptides (AMPs). By transposon screening, identified L. mutants sensitive AMPs. These were impaired in peptidoglycan O-acetylation or teichoic acid D-alanylation, resulting increased negative cell surface charge higher affinity cationic AMP-sensitive cleared from after aging-induced inflammation wild-type, but not AMP-deficient flies, suggesting resistance host AMPs essential for commensal an inflamed environment. Thus, our work reveals addition immune tolerance commensal-encoded necessary maintain stable association between inflammation.

Language: Английский

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Recognition of commensal bacterial peptidoglycans defines Drosophila gut homeostasis and lifespan

PLoS Genetics, Journal Year: 2023, Volume and Issue: 19(4), P. e1010709 - e1010709

Published: April 6, 2023

Commensal microbes in animals have a profound impact on tissue homeostasis, stress resistance, and ageing. We previously showed Drosophila melanogaster that Acetobacter persici is member of the gut microbiota promotes ageing shortens fly lifespan. However, molecular mechanism by which this specific bacterial species changes lifespan physiology remains unclear. The difficulty studying longevity using gnotobiotic flies high risk contamination during To overcome technical challenge, we used bacteria-conditioned diet enriched with products cell wall components. Here, demonstrate an A . -conditioned increases intestinal stem (ISC) proliferation. Feeding adult conditioned , but not Lactiplantibacillus plantarum can decrease increase resistance to paraquat or oral infection Pseudomonas entomophila indicating bacterium alters trade-off between host defence. transcriptomic analysis intestine revealed preferably induces antimicrobial peptides (AMPs), while L upregulates amidase peptidoglycan recognition proteins (PGRPs). induction these Imd target genes peptidoglycans from two due stimulation receptor PGRP-LC anterior midgut for AMPs PGRP-LE posterior PGRPs. Heat-killed also ISC proliferation via PGRP-LC, it sufficient alter resistance. Our study emphasizes significance specificity determining healthspan. It unveils postbiotic effect species, turns into "live fast, die young" lifestyle.

Language: Английский

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Lipopolysaccharide -mediated resistance to host antimicrobial peptides and hemocyte-derived reactive-oxygen species are the major Providencia alcalifaciens virulence factors in Drosophila melanogaster

PLoS Pathogens, Journal Year: 2022, Volume and Issue: 18(9), P. e1010825 - e1010825

Published: Sept. 9, 2022

Bacteria from the genus Providencia are ubiquitous Gram-negative opportunistic pathogens, causing “travelers’ diarrhea”, urinary tract, and other nosocomial infections in humans. Some strains have also been isolated as natural pathogens of Drosophila melanogaster . Despite clinical relevance extensive use immunity research, little is known about virulence mechanisms corresponding insect host defenses. To close this knowledge gap, we investigated factors a representative species— P alcalifaciens which highly virulent to fruit flies amenable genetic manipulations. We generated transposon mutant library performed an unbiased forward genetics screen vivo for attenuated mutants. Our uncovered 23 mutants with reduced virulence. The vast majority them had disrupted genes linked lipopolysaccharide (LPS) synthesis or modifications. These LPS were sensitive cationic antimicrobial peptides (AMPs) vitro their was restored lacking most AMPs. Thus, LPS-mediated resistance AMPs one strategies Another subset exhibited increased susceptibility reactive oxygen species (ROS) rescued by chemical scavenging ROS prior infection. Using analysis, found that enzyme Duox specifically hemocytes source bactericidal targeting Consistently, ROS-sensitive knockdown hemocytes. Therefore, these function helping bacteria counteract immune response. reciprocal analysis host-pathogen interactions between D identified hemocyte-derived major defense against , while ability pathogen resist responses its mechanism. our work revealed conflict mediated

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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Different Long-Term Nutritional Regimens of Drosophila melanogaster Shape Its Microbiota and Associated Metabolic Activity in a Sex-Specific Manner

Insects, Journal Year: 2025, Volume and Issue: 16(2), P. 141 - 141

Published: Feb. 1, 2025

The dietary habits of fruit flies profoundly influence their fitness, morphology, and physiology yet the mechanisms underlying these effects remain incompletely understood. To address this gap, relationship between regimens composition function adult Drosophila melanogaster microbiota was investigated in present study. fly communities that were reared for long time on five different diets characterized by means 16S rRNA sequencing. Obtained results revealed distinct community structures associated with each regimen, which additionally corroborated through machine learning-based analysis. In general, sugar-rich correlate microbial ecosystems higher richness/diversity. Dominance phyla Proteobacteria Firmicutes confirmed irrespective diet, varying proportions most abundant families: Acetobacteraceae, Lactobacillaceae, Moraxellaceae, Bradyrhizobiaceae, Leucostonocaceae. Bacterial families lower abundance also emerged as differentially among studied groups. Additionally, functional prediction provided initial clues into how nutrient availability might modulate metabolic traits a sex-specific manner to meet host needs. Overall, presented findings highlight intricate interplay composition, phenotype flies, underscoring importance diet determinant host-microbiota interactions.

Language: Английский

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Alzheimer's disease and gut-brain axis: Drosophila melanogaster as a model

Frontiers in Neuroscience, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 4, 2025

Research indicates that by 2050, more than 150 million people will be living with Alzheimer's disease (AD), a condition associated neurodegeneration due to the accumulation of amyloid-beta and tau proteins. In addition genetic background, endocrine disruption, cellular senescence, management gut microbiota has emerged as key element in diagnosis, progression, treatment AD, certain bacterial metabolites can travel through bloodstream cross blood-brain barrier. This mini-review explores relationship between protein dysbiosis Drosophila melanogaster . model facilitates investigation how gut-derived contribute neurocognitive impairment dementia. Understanding role direct indirect by-products, such lactate acetate, glial cell activation dynamics may provide insights into mechanisms AD progression effective treatments. Here we discuss simplicity extensive tools make it valuable for studying these interactions testing potential therapeutics, including probiotics. Integrating studies other established models reveal conserved pathways accelerate translation findings clinical applications.

Language: Английский

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Different Species of Yeast Alter the Lifespan and Fecundity of Drosophila melanogaster

Biology Bulletin Reviews, Journal Year: 2025, Volume and Issue: 15(1), P. 109 - 128

Published: Feb. 1, 2025

Language: Английский

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Drosophila symbionts in infection: when a friend becomes an enemy

Infection and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: April 2, 2025

The insect microbiome is comprised of extracellular microbial communities that colonize the host surfaces and endosymbionts reside inside cells tissues. Both these participate in essential aspects biology, including immune response interactions with pathogens. In recent years, our knowledge about role infection has increased tremendously. While many studies have highlighted microbiome's protective effect against various natural enemies insects, unexpected discoveries shown some members microbiota can facilitate pathogenic infections. Here, we summarize fruit fly, Drosophila melanogaster, substantially progressed understanding host-pathogen-microbiome during infection. We on mechanisms gut microbiota, highlight examples exploitation by pathogens, detail endosymbiont-mediated protection. addition, delve into a previously neglected topic research-the crosstalk between microbiota. Finally, address how remain resilient to responses stably By examining influenced reciprocally affects outcomes, this review provides timely cohesive coverage roles

Language: Английский

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Honey bee (Apis mellifera) queen quality: host-microbial transcriptomes exploring the influence of age and hindgut symbiont Commensalibacter melissae

Animal Microbiome, Journal Year: 2025, Volume and Issue: 7(1)

Published: May 2, 2025

Language: Английский

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