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Series GSE85342 Query DataSets for GSE85342
Status Public on Aug 10, 2016
Title A High-Content, Phenotypic Screen Identifies Fluorouridine as an Inhibitor of Pyoverdine Biosynthesis and Pseudomonas aeruginosa Virulence
Organism Caenorhabditis elegans
Experiment type Expression profiling by array
Summary 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.
Overall design 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.
Contributor(s) Kirienko NV
Citation(s) 27579370
NIH grant(s)
Grant ID Grant title Affiliation Name
K22 AI110552 Mechanisms of Stimulating Innate Immunity RICE UNIVERSITY KIRIENKO
Submission date Aug 09, 2016
Last update date Nov 09, 2016
Contact name Natalia V Kirienko
Organization name Rice University
Department BioSciences
Lab Kirienko
Street address 6100 Main St. MS140
City Houston
State/province TX
ZIP/Postal code 77005
Country USA
Platforms (1)
GPL200 [Celegans] Affymetrix C. elegans Genome Array
Samples (6)
GSM2265426 N2_DMSO_A
GSM2265427 N2_DMSO_B
GSM2265428 N2_DMSO_C
BioProject PRJNA338228

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE85342_RAW.tar 11.6 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table

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