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Transcriptomics analysis reveals the molecular mechanisms of the antibacterial activity of gallium nitrate against Acinetobacter baumannii isolated from bloodstream infections

ABSTRACT: Purpose: The aim of this study was to explore the antibacterial effect and molecular mechanism of gallium nitrate [Ga(NO 3 ) 3 ] against Acinetobacter baumannii from bloodstream infection. Methods: A total of 40 A. baumannii with different antimicrobials susceptibility patterns were isolated from bloodstream infections. In vitro antibacterial effect of Ga(NO 3 ) 3 was analyzed by micro-dilution method and time-kill assay. The effect of ferric chloride/heme on the antibacterial effect of Ga(NO 3 ) 3 was evaluated. Transcriptome sequencing was performed to elucidate the antibacterial mechanism of gallium nitrate. Mouse infection model was conducted to explore the in vivo efficacy of gallium nitrate . Results: Ga(NO 3 ) 3 exhibited excellent antibacterial effect in RPMI 1 640 medium containing 10% human serum (MICs ranged from 0.06 μg/mL to 0.125 μg/mL), whereas its antibacterial effect was weakened by exogenous ferric chloride/heme. Ga(NO 3 ) 3 inhibited A. baumannii growth in a dose- and time- dependent manner. Ga(NO 3 ) 3 exerted antibacterial effect by up-regulating the expression of genes associated with biosynthesis and transport of siderophore and disrupting multiple iron dependent metabolism processes. Ga(NO 3 ) 3 significantly reduced bacterial load in the neutropenic mouse thigh infection model. Conclusions: This study revealed that Ga(NO 3 ) 3 had excellent antibacterial activity both in vivo and in vitro . It might be a potential drug for treating bloodstream infections of A. baumannii

ORGANISM(S): Acinetobacter baumannii

PROVIDER: GSE194255 | GEO | 2022/01/27

REPOSITORIES: GEO

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Outer membrane vesicle of Pseudomonas aerugionsa

Project description:Objectives: This study aimed to investigate the microbiological characteristics of outer membrane vesicles (OMVs) derived from Pseudomonas aeruginosa (P. aeruginosa) to understand their mechanisms of inhibition of Acinetobacter baumannii (A. baumannii) in vitro. Methods: We assessed the inhibitory effects of P. aeruginosa on A. baumannii using a modified cross-streak assay. Subsequently, OMVs were extracted from P. aeruginosa strains using high-speed centrifugation, tangential flow filtration, ultrafiltration, and ultracentrifugation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), transmission electron microscopy (TEM), and nanoparticle tracking assays (NTAs) were performed to confirm the presence of the extracted OMVs. P. aeruginosa-derived OMVs’ inhibitory activity against A. baumannii was tested using a modified time-kill assay. The proteomic analysis of OMVs revealed potential antibacterial protein clusters with diverse functions. Results: P. aeruginosa 022 (PA022) demonstrated inhibition of A. baumannii in the cross-streak assay. The protein levels of OMVs for PA022 and P. aeruginosa ATCC 27853 (PA ATCC 27853) were 1665 and 428.6 μg/mL, respectively. Additionally, PA 022 and PA ATCC 27853 exhibited variable patterns and sizes in the SDS-PAGE, TEM, and NTA. Furthermore, the growth inhibitory effect of PA022 OMVs on A. baumannii was evaluated using a modified time-kill assay. The proteomic analysis of OMVs revealed potential antibacterial protein clusters in PA 022 associated with virulence, motility, and post-translational modifications. Conclusion: Our study contributes to the understanding of P. aeruginosa OMVs characteristics and their inhibitory effect against A. baumannii, providing insights into the development of alternative therapeutic approaches against multi-drug resistance.

2023-09-18 | PXD045094 | Pride

citrate vs nitrate Reducing cultures

2010-01-01 | GSE18339 | GEO

citrate vs nitrate Reducing cultures

Project description:The effect of nitrate reduction (anaerobic cultivation in the presence of heme, vitamin K2 and nitrate) was compared with anaerobic cultivation supplemented with citrate (Lactobacillus plantarum). The medium was chemically defined medium with mannitol as main carbon source Two-condition experiment, nitrate vs citrate reducing cells. Biological replicates: 4 nitrate reducing cultures, 4 citrate reducing cultures, independently grown and harvested. Two slides were used, each slide contained 8 Arrays. Citrate reducing cultures are called reactor 1-4, Nitrate reducing cultures are called reactor A-D

2010-05-16 | E-GEOD-18339 | biostudies-arrayexpress

Expression data of Tfe3/Tfeb- or GFP-knocked-down RAW264 macrophages treated with or without iron

Project description:In an attempt to elucidate the role of MiT/TFE families in the iron-mediated phenotypic changes of macrophages, we performed DNA microarray analysis using ferric chloride-stimulated RAW264 cells transfected with Tfe3/Tfeb or GFP. A number of genes upregulated by ferric chloride treatment in siGFP-transfected RAW264 cells were decreased in siTfe3/Tfeb-transfected cells, suggesting MiT/TFE families are involved in phenotypic changes of macrophages induced by iron.

2021-01-27 | GSE157472 | GEO

Tn-Seq of Benzalkonium Chloride Treated and Untreated Acinetobacter baumannii

Project description:The goal of this Tn-Seq study was to determine important determinants of Acinetobacter baumannii tolerance of sub-MIC concentrations of benzalkonium chloride. This Tn-seq data was then utilized to aide in the determination of the sub-MIC mechanism of action for benzalkonium chloride.

2018-01-23 | GSE96745 | GEO

RNA-Seq of Benzalkonium Chloride Treated and Untreated Acinetobacter baumannii

Project description:The goal of this RNA-Seq study was to determine Acinetobacter baumannii's transcriptiional response to sub-MIC concentrations of benzalkonium chloride in Acinetobacter baumannii. This RNA-seq data was then utilized to aide in the determination of the sub-MIC mechanism of action for benzalkonium chloride.

2018-01-23 | GSE96746 | GEO

Transcriptomics analysis reveals the molecular mechanisms of the antibacterial activity of gallium nitrate against Acinetobacter baumannii isolated from bloodstream infections

Project description:Transcriptomics analysis reveals the molecular mechanisms of the antibacterial activity of gallium nitrate against Acinetobacter baumannii isolated from bloodstream infections

| PRJNA800015 | ENA

Expression data of Soybean (Glycine max) roots from different iron treatments.

Project description:Two Near Isogenic soybean (Glycine max) lines were grown in hydroponic conditions with either 50uM ferric nitrate or 100uM ferric nitrate. After 10 days, half the plants were harvested (total root tissue). At 12 days after planting, iron was added to plants grown in low iron conditions bringing them up to sufficient iron growth conditions. Root tissue was harvested for the remaining plants at 14 days after planting. Gene expression analysis from root tissue of two Near Isogenic Lines (NILs), Clark (PI548553) and IsoClark (PI547430), grown in iron stress or iron stress recovered conditions.

2010-09-06 | GSE22227 | GEO

Phenotypic and transcriptional analysis of the antimicrobial effect of lactic acid bacteria on carbapenem-resistant Acinetobacter baumannii: Lacticaseibacillus rhamnosus CRL 2244 an alternative strategy to fight it

Project description:Carbapenem-resistant Acinetobacter baumannii (CRAB) is a recognized nosocomial pathogen with limited therapeutics options. Lactic acid bacteria (LAB) constitute a promising therapeutic alternative. Here we aimed to study the antibacterial properties of a collection of LAB strains using phenotypic and transcriptomic analysis against A. baumannii clinical strains. One strain, Lacticaseibacillus rhamnosus CRL 2244, exerts a strong inhibitory capacity on A. baumannii with a strong killing activity. Scanning electron microscopy images showed changes in the morphology of A. baumannii with an increase formation of outer membrane vesicles. Significant changes in the expression levels a wide variety of genes were observed. Interestingly, most of the modified genes were involved in metabolic pathway known to be associated with bacterial survival. The paa operon, Hut system, and fatty acid degradation were some of the pathways that have been induced. The data reveals the impact of Lcb. rhamnosus CRL 2244 on A. baumannii response, resulting in bacterial stress and subsequent cell death. These findings highlight the antibacterial properties of Lcb. rhamnosus CRL 2244 and its potential as an alternative or complementary strategy for treating infections. Further exploration and development of this LAB as a treatment option could provide valuable alternatives for combating CRAB infections.

2023-09-14 | GSE236782 | GEO

Xanthocillin X Effectively Kills A.Baumannii via Dysregulation of Heme Biosynthesis

Project description:Isonitrile natural products exhibit promising antibacterial activities, however, their mode of action (MoA) remains largely unknown. Based on the nanomolar potency of xanthocillin X (Xan) against diverse difficult-to-treat Gram-negative bacteria, including the critical priority pathogen Acinetobacter baumannii, we performed in-depth studies to decipher its MoA. While neither metal binding nor cellular protein targets were relevant for Xan´s antibiotic effects, sequencing of resistant strains revealed a conserved mutation in the heme biosynthesis enzyme porphobilinogen synthase (PbgS). This mutation caused impaired enzymatic efficiency indicative of reduced heme production. This discovery led to the validation of an untapped mechanism by which direct heme sequestration of Xan prevents its binding into cognate enzyme pockets resulting in uncontrolled cofactor biosynthesis, accumulation of porphyrins and corresponding stress with deleterious effects for bacterial viability. Thus, Xan represents a promising antibiotic displaying activity even against multidrug resistant strains while exhibiting low toxicity to human cells.

2021-09-09 | PXD021400 | Pride

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