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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Cellular and molecular organization of the Drosophila foregut

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(11)

Published: March 5, 2024

The animal foregut is the first tissue to encounter ingested food, bacteria, and viruses. We characterized adult Drosophila using transcriptomics better understand how it triages consumed items for digestion or immune response manages resources. Cell types were assigned validated GFP-tagged Gal4 reporter lines. Foregut-associated neuroendocrine cells play a major integrative role by coordinating gut activity with nutrition, microbiome, circadian cycles; some express clock genes. Multiple epithelial cell comprise proventriculus, central organ that secretes peritrophic matrix (PM) lining gut. Analyzing synthesizing individual PM layers revealed abundant mucin production close enterocytes, similar mammalian intestinal mucosa. esophagus salivary gland secreted proteins likely line esophageal surface, of which may generate commensal niche housing specific microbiome species. Overall, our results imply coordinates dietary sensing, hormonal regulation, immunity in manner has been conserved during evolution.

Language: Английский

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Colonization island directs L. plantarum to its niche

Cell Host & Microbe, Journal Year: 2025, Volume and Issue: 33(2), P. 168 - 170

Published: Feb. 1, 2025

Language: Английский

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Hundreds of antimicrobial peptides create a selective barrier for insect gut symbionts

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(25)

Published: June 12, 2024

The spatial organization of gut microbiota is crucial for the functioning ecosystem, although mechanisms that organize bacterial communities in microhabitats are only partially understood. insect Riptortus pedestris has a characteristic biogeography with multispecies community anterior midgut and monospecific population posterior midgut. We show region produces massively hundreds specific antimicrobial peptides (AMPs), Crypt-specific Cysteine-Rich (CCRs) have membrane-damaging activity against diverse bacteria but symbionts elevated resistance. determined by transposon-sequencing genetic repertoire symbiont Caballeronia insecticola to manage CCR stress, identifying different independent pathways, including AMP-resistance pathways unrelated known membrane homeostasis functions as well cell envelope functions. Mutants corresponding genes reduced capacity colonize midgut, demonstrating CCRs create selective barrier resistance symbionts. Moreover, once established gut, differentiate into CCR-sensitive state, suggesting second function peptide arsenal protecting epithelia or mediating metabolic exchanges between host Our study highlights evolution an extreme AMP family likely contributes establish control microbiota.

Language: Английский

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The endosymbiont Spiroplasma poulsonii increases Drosophila melanogaster resistance to pathogens by enhancing iron sequestration and melanization

mBio, Journal Year: 2024, Volume and Issue: 15(8)

Published: June 28, 2024

ABSTRACT Facultative endosymbiotic bacteria, such as Wolbachia and Spiroplasma species, are commonly found in association with insects can dramatically alter their host physiology. Many endosymbionts defensive protect hosts against parasites or pathogens. Despite the widespread nature of insect symbioses importance for ecology evolution insects, mechanisms symbiont-mediated protection remain poorly characterized. Here, we utilized fruit fly Drosophila melanogaster its facultative endosymbiont poulsonii to characterize underlying bacterial fungal Our results indicate a variable effect S. on infection outcome, endosymbiont-harboring flies being more resistant Rhyzopus oryzae , Staphylococcus aureus, Providencia alcalifaciens but sensitive endosymbiont-free infections Pseudomonas species. Further focusing protective effect, identified Transferrin-mediated iron sequestration induced by crucial defense R. P. . In case aureus enhanced melanization -harboring plays major role protection. Both require immune sensor protease Persephone, suggesting proteases secreted symbiont activation reactions. Hence, our work reveals broader range than previously appreciated adds nutritional immunity arsenal symbionts. IMPORTANCE Defensive bacteria conferring pathogens populations. However, which most symbionts confer not fully understood. studied mediated We demonstrate that besides described wasps nematodes, also confers increased resistance pathogenic fungi. -induced key mechanisms. broadens known spectrum unappreciated endosymbiont-mediated propose have here may be significance could apply other endosymbionts, particularly potentially explain properties.

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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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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Humidity determines penetrance of a latitudinal gradient in genetic selection on the microbiota byDrosophila melanogaster

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 3, 2024

Abstract The fruit fly Drosophila melanogaster is a model for understanding how hosts and their microbial partners interact as the host adapts to wild environments. These interactions are readily interrogated because of low taxonomic numeric complexity flies’ bacterial communities. Previous work has established that genotype, environment, diet, interspecies can all influence fitness microbiota composition, but specific processes characters mediating these incompletely understood. Here, we compared variation in composition between wild-derived populations when flies could choose microorganisms diets were reared under environmental perturbation (different humidities). We also colonization resident transient microorganisms. show ability diet condition relative abundance microbiota. There key differences abundances However, only differed at humidities or above 50% humidity. elevated humidity determined penetrance gradient genetic selection on associated with latitude collected from. Finally, treatment-dependent stress survival. Together, findings emphasize animal be patterned source geography, such potential survival wild. Importance adapt Our what causes geographic remains incomplete. shown D. relatively numerical complexity. Variation attributed variation, location flies. In this explored three possible composition. feeding choices, niche colonized by bacteria, single character contribute latitudinally-patterned observed humidities. results identify several factors genotypes interplay determining hosts.

Language: Английский

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Spatial and temporal coordination of Duox/TrpA1/Dh31 and IMD pathways is required for the efficient elimination of pathogenic bacteria in the intestine of Drosophila larvae

eLife, Journal Year: 2024, Volume and Issue: 13

Published: June 17, 2024

Multiple gut antimicrobial mechanisms are coordinated in space and time to efficiently fight foodborne pathogens. In Drosophila melanogaster , production of reactive oxygen species (ROS) peptides (AMPs) together with intestinal cell renewal play a key role eliminating microbes. A complementary mechanism would be isolate treat pathogenic bacteria while allowing colonization by commensals. Using real-time imaging follow the fate ingested bacteria, we demonstrate that commensal Lactiplantibacillus plantarum freely circulate within lumen, strains such as Erwinia carotovora or Bacillus thuringiensis blocked anterior midgut where they rapidly eliminated peptides. This sequestration requires Duox enzyme enterocytes, both TrpA1 Dh31 enteroendocrine cells. Supplementing larval food hCGRP, human homolog Dh31, is sufficient block suggesting existence conserved mechanism. While immune deficiency (IMD) pathway essential for trapped it dispensable blockage. Genetic manipulations impairing bacterial compartmentalization result abnormal posterior regions bacteria. Despite functional IMD pathway, this ectopic leads proliferation death, demonstrating critical defense. Our study reveals temporal orchestration during which but not innocuous, confined part an IMD-pathway-dependent manner.

Language: Английский

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Hundreds of antimicrobial peptides create a selective barrier for insect gut symbionts

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

Published: Oct. 16, 2023

Abstract The spatial organization of gut microbiota is crucial for the functioning ecosystem, although mechanisms that organize bacterial communities in microhabitats are only partially understood. insect Riptortus pedestris has a characteristic biogeography with multispecies community anterior midgut and mono-specific population posterior midgut. We show region produces massively hundreds specific antimicrobial peptides (AMPs), Crypt-specific Cysteine-Rich (CCRs) have membrane-damaging activity against diverse bacteria but symbionts elevated resistance. determined by transposon-sequencing genetic repertoire symbiont Caballeronia insecticola to manage CCR stress, identifying different independent pathways, including novel AMP-resistance pathways unrelated known membrane homeostasis functions as well cell envelope functions. Mutants corresponding genes reduced capacity colonize midgut, demonstrating CCRs create selective barrier resistance symbionts. Moreover, once established gut, differentiate into CCR-sensitive state, suggesting second function peptide arsenal protecting epithelia or mediating metabolic exchanges between host Our study highlights evolution an extreme AMP family contributes establish control microbiota.

Language: Английский

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