Bloodstream infection in leukemia
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA477837 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR7421920.fastq.gz | Fastqsanger.gz | |||
| SRR7421930.fastq.gz | Fastqsanger.gz | |||
| SRR7421921.fastq.gz | Fastqsanger.gz | |||
| SRR7421931.fastq.gz | Fastqsanger.gz | |||
| SRR7421922.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: The goal of this study was to identify Staphylococcus aureus genes which are important during establishment of metastatic infections in bloodstream infections. Methods: Pooled mariner transposon mutant libraries were generated as previously described (PMID: 27185949). The libraries were sequenced on the Illumina HiSeq 2500 platform with the transposon-specific oligonucleotide primer Himar1-Seq. Illumina adapter sequences were removed via cutadapt version 1.2.1. The reads were filtered for size (>16 bp) and to contain the signature transposon inverted repeat. Reads were mapped to the Staphylococcus aureus 6850 genome (RefSeq accession NC_022222.1) by Bowtie2 v2.1.0. Identification of depleted and enriched mutants was performed via DESeq2 version 1.6.2. Results: S. aureus genes were identified which were upregulated or downregulated upon iduced expression of the LysR-type transcriptional regulator RSAU_000852 in Staphylococcus aureus 6850. Conclusions: Our study identifies a gene for a LysR-type transcription regulator, which is involved in metabolic adaptation of the pathogen during colonization of secondary infection sites in a bloodstream infection model.
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Project description:Serratia marcescens is a bacterium frequently found in the environment, but over the last several decades it has evolved into a concerning clinical pathogen, causing fatal bacteremia. To establish such infections, pathogens require specific nutrients; one very limited but essential nutrient is iron. We sought to characterize the iron acquisition systems in S. marcescens isolate UMH9, which was recovered from a clinical bloodstream infection. Using RNA sequencing (RNA-seq), we identified two predicted siderophore gene clusters (cbs and sch) that were regulated by iron. Mutants were constructed to delete each iron acquisition locus individually and in conjunction, generating both single and double mutants for the putative siderophore systems. Mutants lacking the sch gene cluster lost their iron-chelating ability as quantified by the chrome azurol S (CAS) assay, whereas the cbs mutant retained wild-type activity. Mass spectrometry-based analysis identified the chelating siderophore to be serratiochelin, a siderophore previously identified in Serratia plymuthica. Serratiochelin-producing mutants also displayed a decreased growth rate under iron-limited conditions created by dipyridyl added to LB medium. Additionally, mutants lacking serratiochelin were significantly outcompeted during cochallenge with wild-type UMH9 in the kidneys and spleen after inoculation via the tail vein in a bacteremia mouse model. This result was further confirmed by an independent challenge, suggesting that serratiochelin is required for full S. marcescens pathogenesis in the bloodstream. Nine other clinical isolates have at least 90% protein identity to the UMH9 serratiochelin system; therefore, our results are broadly applicable to emerging clinical isolates of S. marcescens causing bacteremia.
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Project description:We have performed LC-MS based plasma proteomics of twenty febrile patients coming in at Peijas Hospital, Helsinki University Hospital (Vantaa, Finland). At the same time, blood culture was performed to classify the patients to blood culture positive and negative for bloodstream infections. Blood culture negative patients served as controls for the positive ones and these two groups were used for identifying protein profile changes occurring in positive patients. We have subsequently performed various statistical analyses such as principal component analysis as well as pathway analysis by two different methods. We show, in the current study, proteins significantly differing in these two groups as well as dysregulated pathways. These changes seem not to depend on bacterial species as different patients had different blood stream infections. Further, we statistically analyzed the proteomic dataset to find the potential biomarkers which can classify the two classes of patients.
2017-02-28 | PXD005022 | Pride
Project description:We have performed LC-MS based plasma proteomics of twenty febrile patients coming in at Peijas Hospital, Helsinki University Hospital (Vantaa, Finland). At the same time, blood culture was performed to classify the patients to blood culture positive and negative for bloodstream infections. Blood culture negative patients served as controls for the positive ones and these two groups were used for identifying protein profile changes occurring in positive patients. We have subsequently performed various statistical analyses such as principal component analysis as well as pathway analysis by two different methods. We show, in the current study, proteins significantly differing in these two groups as well as dysregulated pathways. These changes seem not to depend on bacterial species as different patients had different blood stream infections. Further, we statistically analyzed the proteomic dataset to find the potential biomarkers which can classify the two classes of patients.
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Project description: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
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