biomedical and healthCAre Data Discovery Index Ecosystem
biomedical and healthCAre Data Discovery Index Ecosystem
| Title: | A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence
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| dateReleased: |
08-10-2016
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| description: |
Pseudomonas aeruginosa is an opportunistic pathogen that causes severe health problems. Despite intensive investigation, many aspects of microbial virulence remain poorly understood. We used a high-throughput, high-content, whole-organism, phenotypic screen to identify small molecules that inhibit P. aeruginosa virulence in C. elegans. Approximately half of the hits were known antimicrobials. A large number of hits were non-antimicrobial bioactive compounds, including the cancer chemotherapeutic 5-fluorouracil. We determined that 5-fluorouracil both transiently inhibits bacterial growth and reduces pyoverdine biosynthesis. Pyoverdine is a siderophore that regulates the expression of several virulence determinants and is critical for pathogenesis in mammals. We show that 5-fluorouridine, a downstream metabolite of 5-fluorouracil, is responsible for inhibiting pyoverdine biosynthesis. We also show that 5-fluorouridine, in contrast to 5-fluorouracil, is a genuine anti-virulent compound, with no bacteriostatic or bacteriocidal activity. To our knowledge, this is the first report utilizing a whole-organism screen to identify novel compounds with antivirulent properties effective against P. aeruginosa. There are 6 samples total that comprise three biological replicates of N2 animals exposed to DMSO or 5-fluorouracil for 8 hours at 25°C. Each biological replicate consists of N2 C. elegans animals in the young adult developmental stage.
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| privacy: |
not applicable
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| aggregation: |
instance of dataset
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| ID: |
E-GEOD-85342
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| refinement: |
raw
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| alternateIdentifiers: |
85342
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| keywords: |
functional genomics
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| dateModified: |
08-13-2016
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| availability: |
available
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| types: |
gene expression
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| name: |
Caenorhabditis elegans
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| ID: |
A-AFFY-60
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| name: |
Affymetrix GeneChip C. elegans Genome Array [Celegans]
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| accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-85342/E-GEOD-85342.raw.1.zip |
| storedIn: |
ArrayExpress
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| qualifier: |
gzip compressed
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| format: |
TXT
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| accessType: |
download
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| authentication: |
none
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| authorization: |
none
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| accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-85342/E-GEOD-85342.processed.1.zip |
| storedIn: |
ArrayExpress
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| qualifier: |
gzip compressed
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| format: |
TXT
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| accessType: |
download
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| authentication: |
none
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| authorization: |
none
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| accessURL: | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE85342 |
| storedIn: |
Gene Expression Omnibus
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| qualifier: |
not compressed
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| format: |
HTML
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| accessType: |
landing page
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| primary: |
true
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| authentication: |
none
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| authorization: |
none
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| abbreviation: |
EBI
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| homePage: | http://www.ebi.ac.uk/ |
| ID: |
SCR:004727
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| name: |
European Bioinformatics Institute
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| homePage: | https://www.ebi.ac.uk/arrayexpress/ |
| ID: |
SCR:002964
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| name: |
ArrayExpress
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