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Peptide YY: a Paneth cell antimicrobial peptide that maintains Candida gut commensalism.

ABSTRACT: The mammalian gut secretes a family of multifunctional peptides that affect appetite, intestinal secretions, and motility, while some regulate the microbiota. We report peptide YY (PYY1-36), but not endocrine PYY3-36, is an antimicrobial peptide (AMP) expressed by gut epithelial Paneth Cells (PC). PC-PYY has limited antibacterial activity, but shows selective activity against virulent hyphal, but not yeast forms, of Candida albicans. 5 PC-PYY is a cationic molecule that interacts with the anionic surfaces of fungal hyphae to cause membrane disruption and transcriptional reprogramming to maintain the yeast phenotype of the fungus. PC-PYY is packaged into secretory granules and is secreted into and retained by surface mucus, which optimizes PC-PYY activity. Hence, PC-PYY acts as a selective antifungal AMP that contributes to the maintenance of gut fungal commensalism.

ORGANISM(S): Candida albicans

PROVIDER: GSE229566 | GEO | 2024/02/28

REPOSITORIES: GEO

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Convergent evolution of peptide-based quorum sensing required for virulence in a eukaryotic pathogen

Project description:Bacterial quorum sensing (QS) systems are characterized by the regulated biogenesis and sensing of specialized signaling molecules. Here, we describe a peptide, Qsp1, secreted by the fungal pathogen Cryptococcus neoformans. Mutants lacking Qsp1 are attenuated for infection, pulmonary accumulation, and growth within macrophages. Qsp1 promotes density-dependent cell wall integrity and resistance to extreme environments. Qsp1 is also required for a secreted aspartyl protease activity required for virulence. Further biochemical and large-scale genetic investigations reveal that cleavage of Qsp1 from the C-terminal of a pro-peptide requires a cell-associated serine protease and Qsp1 sensing requires a predicted oligopeptide importer. Strikingly, these features closely mirror the hallmarks of a peptide-based QS system found in gram-positive bacteria, despite no ancestral relationship between individual components. Our studies thus reveal a convergently evolved, peptide-based QS system required for the virulence of a fungal pathogen.

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Next Generation Sequencing of wild type (WT) and K14 conditional Il9ra-/- mice ear epidermal cell layers

Project description:Complex interactions of keratinocytes with various cells like inflammatory cells and stromal cells contribute to the pathogenesis of chronic inflammatory dermatoses. In proinflammatory cytokines mediating such ill settings, interleukin (IL)-9 plays a pathological role in inflammatory dermatoses. However, IL-9-related mechanisms in such diseases are still incompletely understood. In this study, we established tamoxifen-induced keratinocyte-specific IL-9 receptor alpha-chain-deficient mice (K14CRE/ERTIl9ra∆/∆ mice) to examine the role of IL-9 in multicellular interactions under the condition of chronic skin inflammation. Studies using an imiquimod-induced psoriasis-like model showed that K14CRE/ERTIl9ra∆/∆ mice significantly reduced the severity of dermatitis and mast cell infiltration compared to K14WTIl9rafl/fl mice as controls. The transcriptome analyses of psoriasis-like lesions showed that the level of peptide tyrosine-tyrosine (Pyy), a member of neuropeptide Y family, was markedly downregulated in K14CRE/ERTIl9ra∆/∆ epidermis. Blockade of Pyy suppressed thickening of the epidermis and mast cell number in imiquimod-treated wild-type mice. Together with in vitro studies indicating a capacity of Pyy to induce IL-9 production and chemotactic activity of bone marrow-derived mast cells (BMMCs), these suggest that Pyy-mediated interplay of keratinocytes and mast cells induces psoriasiform inflammation. Further investigation focusing on the IL-9-Pyy axis would provide a new modality for treatment of chronic inflammatory dermatoses.

2022-08-09 | GSE190867 | GEO

RNA-seq analysis of the fungal mycelium of the plant pathogen Pyricularia oryzae treated with and antimicrobial peptide analog of a Trichoderma peptaibol

Project description:We aimed at investigating the mode of action of an antimicrobial peptide analog of a Trichoderma peptaibol. Conidia of P. oryzae (IT10 strain) were cultured in Complete Medium at a final concentration of 2x105 conidia per mL for 3 days at 30 °C under shaking at 150 rpm. After three days, 50 µM of the Peptide 4rink were added to samples containing actively growing mycelium. Untreated samples were used as control. Three h after peptide treatment, fungal mycelia were collected, filtered with 100 µm Cell Strainer (Corning®), rinsed with sterile water and stored at -80 °C for RNA extraction. Total RNA was extracted with the RNeasy Plant Mini kit (Qiagen) following the manufacturer’s instructions, performing the DNase digestion directly on the column. The integrity and concentration of the RNA samples were checked with Qubit fluorimeter and Bioanalyzer. RNA samples with RIN values < 7 were discarded. Four biological replicates of each treatment were submitted to RNA sequencing and analysis at CRIBI Biotechnology Center (University of Padova). Two µg of total RNA were subjected to PolyA tail capture and rRNA depletion for selection of mRNA. Directional (stranded) RNA libraries were prepared, quantified and subjected to quality control. Sequencing was performed on Illumina Nova Seq 6000 platform. Twenty million reads were produced for each sample and checked for quality control. Based on our RNA-seq data, the molecular mechanisms of the fungicidal activity of these peptide analogs appear to be related to their ability to cause cell wall and membrane damages and to induce autophagic cell death in fungal cells. This is the first transcriptomic analysis on a fungus treated with peptaibol analogs.

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Project description:Algesic activity of the human coronavirus OC43 derived peptide

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2023-12-27 | GSE230640 | GEO

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Project description:Antimicrobial peptide resistance in human gut microbial communities

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Antimicrobial peptide resistance in human gut microbial communities

Project description:Antimicrobial peptide resistance in human gut microbial communities

| PRJEB7688 | ENA

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Project description:Antimicrobial peptide ChMAP-28 is a peptide of innate immunity of the goat Capra hircus. The goal of this research was to evaluate possible changes in the molecular signaling pathways in HL-60 leukemia cells and also to correlate this effect with the cytotoxic activity of the peptide.

2018-08-11 | GSE118397 | GEO

RNASeq AMPs

Project description:Transcriptome analysis of Antimicrobial peptide (AMP) treatments

| PRJEB41423 | ENA

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Project description:Background: The hypothalamus is an important brain region for the regulation of energy balance. Roux-en-Y gastric bypass (RYGB) surgery and gut hormone-based treatments are known to reduce body weight, but their effects on hypothalamic gene expression and signaling pathways are poorly studied. Methods: Diet-induced obese male Wistar rats were randomized into the following groups: RYGB, sham-operation, sham + body weight-matched (BWM) to the RYGB group, osmotic minipump delivering PYY3-36 (0.1mg/kg/day), liraglutide s.c. (0.4mg/kg/day), PYY3-36+liraglutide and saline. All groups (except BWM) were kept on a free choice of high- and low-fat diets. Four weeks after interventions, hypothalami were collected for RNA-sequencing. Results: While rats in the RYGB, BWM and PYY3-36+liraglutide groups had comparable reductions in body weight, only RYGB and BWM treatment had a major impact on hypothalamic gene expression. In these groups, hypothalamic leptin receptor expression as well as the JAK–STAT, PI3K-Akt and AMPK signaling pathways were upregulated. No significant changes could be detected in PYY3-36+liraglutide, liraglutide and PYY treated groups. Conclusions: Despite causing similar body weight changes compared to RYGB and BWM, PYY3-36+liraglutide treatment does not impact hypothalamic gene expression. Whether this striking difference is favorable or unfavorable to metabolic health in the long term requires further investigation.

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