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Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection
The nematode Caenorhabditis elegans offers currently untapped potential for carrying out high-throughput, live-animal screens of low molecular weight compound libraries to identify molecules that target a variety of cellular processes. We previously used a bacterial infection assay in C. elegans to...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375230/ https://www.ncbi.nlm.nih.gov/pubmed/22719261 http://dx.doi.org/10.1371/journal.pgen.1002733 |
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author | Pukkila-Worley, Read Feinbaum, Rhonda Kirienko, Natalia V. Larkins-Ford, Jonah Conery, Annie L. Ausubel, Frederick M. |
author_facet | Pukkila-Worley, Read Feinbaum, Rhonda Kirienko, Natalia V. Larkins-Ford, Jonah Conery, Annie L. Ausubel, Frederick M. |
author_sort | Pukkila-Worley, Read |
collection | PubMed |
description | The nematode Caenorhabditis elegans offers currently untapped potential for carrying out high-throughput, live-animal screens of low molecular weight compound libraries to identify molecules that target a variety of cellular processes. We previously used a bacterial infection assay in C. elegans to identify 119 compounds that affect host-microbe interactions among 37,214 tested. Here we show that one of these small molecules, RPW-24, protects C. elegans from bacterial infection by stimulating the host immune response of the nematode. Using transcriptome profiling, epistasis pathway analyses with C. elegans mutants, and an RNAi screen, we show that RPW-24 promotes resistance to Pseudomonas aeruginosa infection by inducing the transcription of a remarkably small number of C. elegans genes (∼1.3% of all genes) in a manner that partially depends on the evolutionarily-conserved p38 MAP kinase pathway and the transcription factor ATF-7. These data show that the immunostimulatory activity of RPW-24 is required for its efficacy and define a novel C. elegans–based strategy to identify compounds with activity against antibiotic-resistant bacterial pathogens. |
format | Online Article Text |
id | pubmed-3375230 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-33752302012-06-20 Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection Pukkila-Worley, Read Feinbaum, Rhonda Kirienko, Natalia V. Larkins-Ford, Jonah Conery, Annie L. Ausubel, Frederick M. PLoS Genet Research Article The nematode Caenorhabditis elegans offers currently untapped potential for carrying out high-throughput, live-animal screens of low molecular weight compound libraries to identify molecules that target a variety of cellular processes. We previously used a bacterial infection assay in C. elegans to identify 119 compounds that affect host-microbe interactions among 37,214 tested. Here we show that one of these small molecules, RPW-24, protects C. elegans from bacterial infection by stimulating the host immune response of the nematode. Using transcriptome profiling, epistasis pathway analyses with C. elegans mutants, and an RNAi screen, we show that RPW-24 promotes resistance to Pseudomonas aeruginosa infection by inducing the transcription of a remarkably small number of C. elegans genes (∼1.3% of all genes) in a manner that partially depends on the evolutionarily-conserved p38 MAP kinase pathway and the transcription factor ATF-7. These data show that the immunostimulatory activity of RPW-24 is required for its efficacy and define a novel C. elegans–based strategy to identify compounds with activity against antibiotic-resistant bacterial pathogens. Public Library of Science 2012-06-14 /pmc/articles/PMC3375230/ /pubmed/22719261 http://dx.doi.org/10.1371/journal.pgen.1002733 Text en Pukkila-Worley et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Pukkila-Worley, Read Feinbaum, Rhonda Kirienko, Natalia V. Larkins-Ford, Jonah Conery, Annie L. Ausubel, Frederick M. Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection |
title | Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection |
title_full | Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection |
title_fullStr | Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection |
title_full_unstemmed | Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection |
title_short | Stimulation of Host Immune Defenses by a Small Molecule Protects C. elegans from Bacterial Infection |
title_sort | stimulation of host immune defenses by a small molecule protects c. elegans from bacterial infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3375230/ https://www.ncbi.nlm.nih.gov/pubmed/22719261 http://dx.doi.org/10.1371/journal.pgen.1002733 |
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