Antimicrobial Peptides—Mechanisms of Action, Antimicrobial Effects and Clinical Applications

Antibiotics, Journal Year: 2022, Volume and Issue: 11(10), P. 1417 - 1417

Published: Oct. 16, 2022

The growing emergence of antimicrobial resistance represents a global problem that not only influences healthcare systems but also has grave implications for political and economic processes. As the discovery novel agents is lagging, one solutions innovative therapeutic options would expand our armamentarium against this hazard. Compounds interest in many such studies are peptides (AMPs), which actually represent host’s first line defense pathogens involved innate immunity. They have broad range activity Gram-negative Gram-positive bacteria, fungi, viruses, with specific mechanisms action utilized by different AMPs. Coupled lower propensity development, it becoming clear AMPs can be seen as emerging very promising candidates more pervasive usage treatment infectious diseases. However, their use quotidian clinical practice without challenges. In review, we aimed to summarize state-of-the-art evidence on structure AMPs, well provide detailed information activity. We present contemporary trials application highlight beyond diseases potential challenges may arise increasing availability.

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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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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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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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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Eucommia Polysaccharides Ameliorate Aging-Associated Gut Dysbiosis: A Potential Mechanism for Life Extension in Drosophila

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(6), P. 5881 - 5881

Published: March 20, 2023

The gut microbiota is increasingly considered to play a key role in human immunity and health. aging process alters the composition, which associated with inflammation, reactive oxygen species (ROS), decreased tissue function, increased susceptibility age-related diseases. It has been demonstrated that plant polysaccharides have beneficial effects on microbiota, particularly reducing pathogenic bacteria abundance increasing populations. However, there limited evidence of effect dysbiosis ROS accumulation during process. To explore Eucommiae (EPs) Drosophila, series behavioral life span assays Drosophila same genetic background standard medium supplemented EPs were performed. Next, composition protein detected using 16S rRNA gene sequencing analysis quantitative proteomic analysis. Here, we show supplementation development leads extension Drosophila. Furthermore, suppressed Gluconobacter, Providencia, Enterobacteriaceae aged Increased indigenous might induce dysfunction shortens their span. Our study demonstrates can be used as prebiotic agents prevent aging-associated oxidative stress.

Language: Английский

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Engineered fungus containing a caterpillar gene kills insects rapidly by disrupting their ecto- and endo-microbiomes

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Aug. 7, 2024

Similar to the physiological importance of gut microbiomes, recent works have shown that insect ectomicrobiotas can mediate defensive colonization resistance against fungal parasites infect via cuticle penetration. Here we show engineering entomopathogenic fungus Metarhizium robertsii with a potent antibacterial moricin gene from silkworms substantially enhances ability kill mosquitos, locusts, and two Drosophila species. Further use melanogaster as an infection model, quantitative microbiome analysis reveals engineered strains designed suppress cuticular bacteria additionally disrupt microbiomes. An overgrowth harmful such opportunistic pathogens Providencia species is detected accelerate death. In support, antimicrobial genes in fly fat bodies guts indicates topical infections result compromise intestinal immune responses. addition providing innovative strategy for improving potency mycoinsecticides, our data solidify both ecto- endo-microbiomes maintaining wellbeing.

Language: Английский

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Pathogenic diversification of the gut commensal Providencia alcalifaciens via acquisition of a second type III secretion system

Infection and Immunity, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 10, 2024

ABSTRACT Providencia alcalifaciens is a Gram-negative bacterium found in various water and land environments organisms, including insects mammals. Some P. strains encode gene homologs of virulence factors pathogenic Enterobacterales members, such as Salmonella enterica serovar Typhimurium Shigella flexneri . Whether these genes are determinants not known. In this study, we investigated –host interactions at the cellular level, focusing on role two type III secretion systems (T3SS) belonging to Inv-Mxi/Spa family. T3SS 1b widespread spp. encoded chromosome. A large plasmid that present subset strains, primarily isolated from diarrheal patients, encodes for 1a We show 205/92 internalized into eukaryotic cells, lyses its internalization vacuole, proliferates cytosol. This triggers caspase-4-dependent inflammasome responses gut epithelial cells. The requirement entry, vacuole lysis, cytosolic proliferation host cell type-specific, playing more prominent intestinal cells than macrophages or insect bovine ligated loop model, colonizes mucosa induces mild damage with negligible fluid accumulation - -independent manner. However, was required rapid killing Drosophila melanogaster propose acquisition has allowed diversify range, highly virulent pathogen an opportunistic gastrointestinal animals.

Language: Английский

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