Red death in Caenorhabditis elegans caused by Pseudomonas aeruginosa PAO1

Alexander Zaborin, Kathleen Romanowski, Svetlana Gerdes, Christopher Holbrook, Francois Lepine, Jason Long, Valeriy Poroyko, Stephen P. Diggle, Andreas Wilke, Karima Righetti, Irina Morozova, Trissa Babrowski, Donald C. Liu, Olga Zaborina, John C. Alverdy

Research output: Contribution to journalArticle

130 Scopus citations

Abstract

During host injury, Pseudomonas aeruginosa can be cued to express a lethal phenotype within the intestinal tract reservoir - a hostile, nutrient scarce environment depleted of inorganic phosphate. Here we determined if phosphate depletion activates a lethal phenotype in P. aeruginosa during intestinal colonization. To test this, we allowed Caenorhabditis elegans to feed on lawns of P. aeruginosa PAOI grown on high and low phosphate media. Phosphate depletion caused PAOI to kill 60% of nematodes whereas no worms died on high phosphate media. Unexpectedly, intense redness was observed in digestive tubes of worms before death. Using a combination of transcriptome analyses, mutants, and reporter constructs, we identified 3 global virulence systems that were involved in the "red death" response of P. aeruginosa during phosphate depletion; they included phosphate signaling (PhoB), the MvfR-PQS pathway of quorum sensing, and the pyoverdin iron acquisition system. Activation of all 3 systems was required to form a red colored PQS+Fe 3+ complex which conferred a lethal phenotype in this model. When pyoverdin production was inhibited in P. aeruginosa by providing excess iron, red death was attenuated in C. elegans and mortality was decreased in mice intestinally inoculated with P. aeruginosa. Introduction of the red colored PQS+Fe 3+ complex into the digestive tube of C. elegans or mouse intestine caused mortality associated with epithelial disruption and apoptosis. In summary, red death in C. elegans reveals a triangulated response between PhoB, MvfR-PQS, and pyoverdin in response to phosphate depletion that activates a lethal phenotype in P. aeruginosa.

Original languageEnglish (US)
Pages (from-to)6327-6332
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number15
DOIs
StatePublished - Apr 14 2009
Externally publishedYes

Keywords

  • Mice
  • P. aeruginosa transcriptome
  • Phosphate depletion
  • PQS/Fe3+
  • Pyoverdin
  • Rhamnolipid complex

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Red death in Caenorhabditis elegans caused by Pseudomonas aeruginosa PAO1'. Together they form a unique fingerprint.

  • Cite this

    Zaborin, A., Romanowski, K., Gerdes, S., Holbrook, C., Lepine, F., Long, J., Poroyko, V., Diggle, S. P., Wilke, A., Righetti, K., Morozova, I., Babrowski, T., Liu, D. C., Zaborina, O., & Alverdy, J. C. (2009). Red death in Caenorhabditis elegans caused by Pseudomonas aeruginosa PAO1. Proceedings of the National Academy of Sciences of the United States of America, 106(15), 6327-6332. https://doi.org/10.1073/pnas.0813199106