Ethanolamine Controls Expression of Genes Encoding Components Involved in Interkingdom Signaling and Virulence in Enterohemorrhagic Escherichia coli O157:H7

Abstract

Bacterial pathogens must be able to both recognize suitable niches within the host for colonization and successfully compete with commensal flora for nutrients in order to establish infection. Ethanolamine (EA) is a major component of mammalian and bacterial membranes and is used by pathogens as a carbon and/or nitrogen source in the gastrointestinal tract. The deadly human pathogen enterohemorrhagic Escherichia coli O157:H7 (EHEC) uses EA in the intestine as a nitrogen source as a competitive advantage for colonization over the microbial flora. Here we show that EA is not only important for nitrogen metabolism but that it is also used as a signaling molecule in cell-to-cell signaling to activate virulence gene expression in EHEC. EA in concentrations that cannot promote growth as a nitrogen source can activate expression of EHEC’s repertoire of virulence genes. The EutR transcription factor, known to be the receptor of EA, is only partially responsible for this regulation, suggesting that yet another EA receptor exists. This important link of EA with metabolism, cell-to-cell signaling, and pathogenesis, highlights the fact that a fundamental means of communication within microbial communities relies on energy production and processing of metabolites. Here we show for the first time that bacterial pathogens not only exploit EA as a metabolite but also coopt EA as a signaling molecule to recognize the gastrointestinal environment and promote virulence expression.

Enterohemorrhagic Escherichia coli Virulence Gene Regulation

“…More recently, ethanolamine, a bacterial and animal cell membrane component that is released into the lumen of the gut upon normal epithelial cell turnover, has been implicated as a molecule important in EHEC virulence gene regulation. Ethanolamine is perceived by EHEC, leading to increased expression of the quorum-sensing regulators QseA, QseC, and QseE and Ler (38). In addition, the LEE operons 1 through 5 are thus stimulated in the presence of ethanolamine.…”

“…In addition, ethanolamine, a cell membrane component, stimulates ler production through EutR and QseC (38). Gluconeogenic conditions of the large intestine activate the ler activators KdpE and Cra, and butyrate directly activates LEE transcriptional activity (37,125).…”

“…In addition, the LEE operons 1 through 5 are thus stimulated in the presence of ethanolamine. Though there are 17 ethanolamine utilization genes, eut, necessary for the use of this compound as a nitrogen source, the observed signaling in EHEC is independent of ethanolamine metabolism, but partially dependent on the EutR transcriptional regulator that binds ethanolamine (38) (Fig. 4).…”

“…QseF can be phosphorylated by either QseE, responding to epinephrine, sulfate, and phosphate, or QseC to stimulate stx2. Ethanolamine, released from epithelium, also stimulates Stx2 production in EHEC (38). The genetic pathway necessary for the signaling involves the ethanolamine utilization regulator eutR, as deletion of the gene encoding this protein resulted in decreased expression of stx2 by microarray (Fig.…”

“…Sulfate, phosphate, and epinephrine molecules signal through the two-component system QseCF to RecA, thus leading activation of Stx2 production. Ethanolamine also upregulates stx2 through the transcription factor EutR (38). doi:10.1128/microbiolspec.EHEC -0004-2013.f5 (130).…”