1. Academic Validation
  2. The Norepinephrine Metabolite 3,4-Dihydroxymandelic Acid Is Produced by the Commensal Microbiota and Promotes Chemotaxis and Virulence Gene Expression in Enterohemorrhagic Escherichia coli

The Norepinephrine Metabolite 3,4-Dihydroxymandelic Acid Is Produced by the Commensal Microbiota and Promotes Chemotaxis and Virulence Gene Expression in Enterohemorrhagic Escherichia coli

  • Infect Immun. 2017 Sep 20;85(10):e00431-17. doi: 10.1128/IAI.00431-17.
Nitesh Sule 1 Sasi Pasupuleti 1 Nandita Kohli 1 Rani Menon 1 Lawrence J Dangott 2 Michael D Manson 3 Arul Jayaraman 4 5
Affiliations

Affiliations

  • 1 Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas, USA.
  • 2 Department of Biochemistry and Biophysics, Texas A&M University, College Station, Texas, USA.
  • 3 Department of Biology, Texas A&M University, College Station, Texas, USA mike@mail.bio.tamu.edu arulj@tamu.edu.
  • 4 Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, Texas, USA mike@mail.bio.tamu.edu arulj@tamu.edu.
  • 5 Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, College Station, Texas, USA.
Abstract

Enterohemorrhagic Escherichia coli (EHEC) is a commonly occurring foodborne pathogen responsible for numerous multistate outbreaks in the United States. It is known to infect the host gastrointestinal tract, specifically, in locations associated with lymphoid tissue. These niches serve as sources of enteric neurotransmitters, such as epinephrine and norepinephrine, that are known to increase virulence in several pathogens, including enterohemorrhagic E. coli The mechanisms that allow pathogens to target these niches are poorly understood. We previously reported that 3,4-dihydroxymandelic acid (DHMA), a metabolite of norepinephrine produced by E. coli, is a chemoattractant for the nonpathogenic E. coli RP437 strain. Here we report that DHMA is also a chemoattractant for EHEC. In addition, DHMA induces the expression of EHEC virulence genes and increases attachment to intestinal epithelial cells in vitro in a QseC-dependent manner. We also show that DHMA is present in murine gut fecal contents and that its production requires the presence of the commensal microbiota. On the basis of its ability to both attract and induce virulence gene expression in EHEC, we propose that DHMA acts as a molecular beacon to target pathogens to their preferred sites of Infection in vivo.

Keywords

DHMA; EHEC; chemotaxis; interkingdom signaling; norepinephrine; virulence.

Figures
Products