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E-GEOD-85342 - A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence

Status
Released on 10 August 2016, last updated on 13 August 2016
Organism
Caenorhabditis elegans
Samples (6)
Array (1)
Protocols (7)
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.
Experiment type
transcription profiling by array 
Contacts
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-85342.idf.txt
Sample and data relationshipE-GEOD-85342.sdrf.txt
Raw data (1)E-GEOD-85342.raw.1.zip
Processed data (1)E-GEOD-85342.processed.1.zip
Array designA-AFFY-60.adf.txt
Links