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Peptide 1018 disrupts swarming and the swarming-associated, anr-mediated metabolic program of Pseudomonas aeruginosa

ABSTRACT: Peptide 1018 disrupts swarming and the swarming-associated, anr-mediated metabolic program of Pseudomonas aeruginosa

PROVIDER: PRJNA635354 | ENA |

REPOSITORIES: ENA

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Peptide 1018 disrupts swarming and the swarming-associated, anr-mediated metabolic program of Pseudomonas aeruginosa

Project description:Abstract: Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen found ubiquitously in the environment. Responsible for considerable human morbidity and mortality, particularly in nosocomial infections and individuals with cystic fibrosis, P. aeruginosa can adapt to surface growth by undergoing swarming motility. In P. aeruginosa, swarming motility is a rapid multicellular movement that occurs on soft surfaces of appropriate viscosity with amino acids as a nitrogen source. Here we tested the small synthetic host defense peptide, innate defense regulator 1018, and found that it inhibited swarming motility at concentrations as low as 0.75 μg/ml, well below the MIC for planktonic cells. A screen of the PA14 transposon insertion mutant library revealed twenty-nine mutants that demonstrated partial tolerance to 1018 under swarming conditions. Two of these mutants, in the genes anr and rhlB (a regulator of anaerobic metabolism and protein involved in rhamnolipid production, respectively), were complemented to restore susceptibility to 1018. RNA-Seq of peptide-treated cells under swarming conditions revealed the dysregulation of 1,190 genes compared to the untreated swarm front, and 67% of these genes were similarly dysregulated at the untreated swarm centre. In contrast, expression of 70 Anr-regulated genes was upregulated by peptide treatment, and 45 genes showed differential or opposite regulation of expression in peptide-treated and swarm centre cells. Many transcriptional regulators required for swarming were dysregulated in peptide-treated cells, indicative of a mechanism by which 1018 may inhibit swarming motility. Overall, this study illustrates a use for peptide 1018 in inhibiting swarming surface motility, an important bacterial adaptation.

2021-04-20 | GSE151264 | GEO

Rescue Of Dysfunctional Autophagy By Peptide IDR-1018 Attenuates Hyperinflammatory Phenotype Of Cystic Fibrosis Cells (RNA-seq)

2012-11-20 | GSE35394 | GEO

Rescue Of Dysfunctional Autophagy By Peptide IDR-1018 Attenuates Hyperinflammatory Phenotype Of Cystic Fibrosis Cells (RNA-seq)

Project description:Genome-wide gene expression was measured in peripheral blood mononuclear cells (PBMCs) from patients with cystic fibrosis (CF) after treatment in vitro with the flagellin protein fliC, and/or synthetic peptide IDR-1018 to assess patterns of gene expression. The patterns of gene expression suggest that CF cells have a hyperinflammatory phenotype including dysfunctional autophagy processes. The synthetic peptide IDR-1018 attentuates this hyperinflammatory phenotype. Total RNA was obtained from PBMCs obtained from CF patients after treatment with the fliC flagellin protein (that is known to play a role in CF lung inflammation), and/or the peptide IDR-1018 that has anti-inflammatory properties. Comparison of genes and pathways affected by these treatments indicated the role of autophagy process in CF disease.

2012-11-20 | E-GEOD-35394 | biostudies-arrayexpress

Rescue Of Dysfunctional Autophagy By Peptide IDR-1018 Attenuates Hyperinflammatory Phenotype Of Cystic Fibrosis Cells

Project description:Genome-wide gene expression was measured in two cell lines: CF bronchial epithelial cell line IB3-1 (compound heterozygote for the ΔF508 and W1282X CFTR mutations) and the isogenic, CFTR-corrected C38 cell line, after treatment with the flagellin protein FliC, and/or synthetic peptide IDR-1018. Total RNA was obtained from cell lines representing CF and normal epithelial cells after treatment with the fliC protein (that is known to play a role in CF lung inflammation), and/or the peptide IDR-1018 that has anti-inflammatory properties. Comparison of genes and pathways affected by these treatments indicated the role of autophagy process in CF disease.

2012-11-05 | E-GEOD-35391 | biostudies-arrayexpress

Rescue Of Dysfunctional Autophagy By Peptide IDR-1018 Attenuates Hyperinflammatory Phenotype Of Cystic Fibrosis Cells

2012-11-05 | GSE35391 | GEO

Synthetic cationic peptide IDR-1018 modulates human macrophage differentiation

2013-10-16 | GSE40131 | GEO

Peptide 1018 inhibits swarming and influences Anr-regulated gene expression downstream of the stringent stress response in Pseudomonas aeruginosa.

Project description: Not available

| S-EPMC8087004 | biostudies-literature

Synthetic cationic peptide IDR-1018 modulates human macrophage differentiation

Project description:Synthetic, innate defense regulators (IDR) peptides, designed based on natural host defenses peptides, have enhanced immunomodulatory activities and reduced toxicity leading to protection in infection and inflammation models that is dependent on macrophages/monocytes. Here we measured the effect of IDR-1018 on macrophage gene expression during differentiation. Differentiation in the presence of IDR-1018 induced a unique signature of immune responses suggesting that IDR-1018 drives macrophage differentiation towards an intermediate M1-M2 state, enhancing anti-inflammatory functions while maintaining certain pro-inflammatory activities important to the resolution of infection. RNA-seq was performed using the Illumina Genome Analyzer IIx platform. Monocytes were isolated from 3 healthy donors, and left unstimulated or stimulated for 4 hours with 20 μg/ml IDR-1018. For library preparation, 500 ng of total RNA was processed according to the Illumina TruSeq RNA sample preparation guide (Illumina catalogue number FC-122-1002). Briefly, mRNA was purified using poly-dT beads, followed by synthesis of the first and second cDNA strands, end repair addition of an poly-A overhang, and ligation of adapters and unique barcodes, as per the manufacturer’s instructions. DNA enrichment was carried out via a 15-cycle PCR. Following quantification, 8 pM of dsDNA was used for cluster generation on a CBOT instrument (Illumina, San Diego, CA). RNA sequencing was done on a GAIIx instrument (Illumina), performed as a single read run with 51 amplification cycles. Data processing was carried out in house, using CASAVA to convert raw data and demultiplex to FASTQ sequence files. Reads were aligned to the reference genome using TOPHAT, and then mapped to genes using the Bioconductor package GenomeRanges.

2013-10-16 | E-GEOD-40131 | biostudies-arrayexpress

Swarming sample vs non-swarming sample

Project description:Transcriptional profiling of mosquito head comparing control non-swarming mosquito with swarming mosquito. Screen the genes associated with swarming.

2020-09-19 | GSE150971 | GEO

Swarming sample vs non-swarming sample

Project description:Swarming sample vs non-swarming sample

| PRJNA634263 | ENA