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The neuroendocrine hormone norepinephrine increases Pseudomonas aeruginosa PA14 virulence through the las quorum-sensing pathway

  • Applied Microbial and Cell Physiology
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Abstract

It has been proposed that the gastrointestinal tract environment containing high levels of neuroendocrine hormones is important for gut-derived Pseudomonas aeruginosa infections. In this study, we report that the hormone norepinephrine increases P. aeruginosa PA14 growth, virulence factor production, invasion of HCT-8 epithelial cells, and swimming motility in a concentration-dependent manner. Transcriptome analysis of P. aeruginosa exposed to 500 µM, but not 50 µM, norepinephrine for 7 h showed that genes involved in the regulation of the virulence determinants pyocyanin, elastase, and the Pseudomonas quinolone signal (PQS, 2-heptyl-3-hydroxy-4-quinolone) were upregulated. The production of rhamnolipids, which are also important in P. aeruginosa infections, was not significantly altered in suspension cultures upon exposure to 500 µM norepinephrine but decreased on semisolid surfaces. Swarming motility, a phenotype that is directly influenced by rhamnolipids, was also decreased upon 500 µM norepinephrine exposure. The increase in the transcriptional activation of lasR but not that of rhlR and the increase in the levels of PQS suggest that the effects of norepinephrine are mediated primarily through the las quorum-sensing pathway. Together, our data strongly suggest that norepinephrine can play an important role in gut-derived infections by increasing the pathogenicity of P. aeruginosa PA14.

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Acknowledgements

This work was supported by the Texas Engineering Experiment Station (AJ) and the National Institutes of Health (R01 EB003872; TKW). We thank Drs. Akhiro Ueda and Can Attila for help with virulence factor assays and Profs. Mark Lyte and R. Jayaraman for comments and suggestions.

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Authors and Affiliations

  1. Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX, 77843-3122, USA

    Manjunath Hegde, Thomas K. Wood & Arul Jayaraman

  2. Department of Biology, Texas A&M University, College Station, TX, 77843-3258, USA

    Thomas K. Wood

  3. Zachry Department of Civil Engineering, Texas A&M University, College Station, TX, 77843-3136, USA

    Thomas K. Wood

  4. Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77843-3120, USA

    Arul Jayaraman

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  1. Manjunath Hegde
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Correspondence to Arul Jayaraman.

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253_2009_2045_MOESM1_ESM.doc

Supplemental Table I: Complete list of differentially expressed genes above the statistically significant cutoff fold change of 4.0 (based on standard deviation of the fold changes of all the genes) in suspension cells of PA14 grown in serum RPMI medium at 37°C for 7 h with and without 50 µM NE. Complete data for the 50-µM DNA microarrays are available using GEO series accession number GSE 13326 (DOC 27 kb)

253_2009_2045_MOESM2_ESM.doc

Supplemental Table II: Complete list of differentially expressed genes above the statistically significant cutoff fold change of 2.0 (based on standard deviation of the fold changes of all the genes) in suspension cells of PA14 grown in serum RPMI medium at 37°C for 7 h with and without 500 µM NE. Complete data for the 50-µM DNA microarrays are available using GEO series accession number GSE 13326 (DOC 41 kb)

253_2009_2045_MOESM3_ESM.doc

Supplemental Table III: Complete list of common genes differentially expressed above the statistically significant cutoff fold change of 4.0-fold (for 50-µM NE array) and 2.0-fold (for 500-µM NE array) in suspension cells of PA14 grown in serum RPMI medium at 37°C for 7 h with and without 50 µM NE (DOC 17 kb)

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Hegde, M., Wood, T.K. & Jayaraman, A. The neuroendocrine hormone norepinephrine increases Pseudomonas aeruginosa PA14 virulence through the las quorum-sensing pathway. Appl Microbiol Biotechnol 84, 763–776 (2009). https://doi.org/10.1007/s00253-009-2045-1

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