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| 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.
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| 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.
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| 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 |
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| |
| Submission date |
Aug 09, 2016 |
| Last update date |
Nov 09, 2016 |
| Contact name |
Natalia V Kirienko |
| E-mail(s) |
kirienko@rice.edu
|
| 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 |
| |
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| Platforms (1) |
| GPL200 |
[Celegans] Affymetrix C. elegans Genome Array |
|
| Samples (6)
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| Relations |
| BioProject |
PRJNA338228 |
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