The Serotonin Neurotransmitter Modulates Virulence of Enteric Pathogens

Aman Kumar, Regan M. Russell, Reed Pifer, Zelia Menezes-Garcia, Santiago Cuesta, Sanjeev Narayanan, John B. MacMillan, Vanessa Sperandio

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The gut-brain axis is crucial to microbial-host interactions. The neurotransmitter serotonin is primarily synthesized in the gastrointestinal (GI) tract, where it is secreted into the lumen and subsequently removed by the serotonin transporter, SERT. Here, we show that serotonin decreases virulence gene expression by enterohemorrhagic E. coli (EHEC) and Citrobacter rodentium, a murine model for EHEC. The membrane-bound histidine sensor kinase, CpxA, is a bacterial serotonin receptor. Serotonin induces dephosphorylation of CpxA, which inactivates the transcriptional factor CpxR controlling expression of virulence genes, notably those within the locus of enterocyte effacement (LEE). Increasing intestinal serotonin by genetically or pharmacologically inhibiting SERT decreases LEE expression and reduces C. rodentium loads. Conversely, inhibiting serotonin synthesis increases pathogenesis and decreases host survival. As other enteric bacteria contain CpxA, this signal exploitation may be engaged by other pathogens. Additionally, repurposing serotonin agonists to inhibit CpxA may represent a potential therapeutic intervention for enteric bacteria.

Original languageEnglish (US)
Pages (from-to)41-53.e8
JournalCell Host and Microbe
Volume28
Issue number1
DOIs
StatePublished - Jul 8 2020

Keywords

  • CpxA
  • enteric infections
  • enterohemorrhagic E. coli (EHEC)
  • inter-kingdom signaling
  • serotonin

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology

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  • Cite this

    Kumar, A., Russell, R. M., Pifer, R., Menezes-Garcia, Z., Cuesta, S., Narayanan, S., MacMillan, J. B., & Sperandio, V. (2020). The Serotonin Neurotransmitter Modulates Virulence of Enteric Pathogens. Cell Host and Microbe, 28(1), 41-53.e8. https://doi.org/10.1016/j.chom.2020.05.004