4 years ago

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

Kohli N, Manson MD, Jayaraman A, Pasupuleti S, Dangott LJ, Sule N, Menon R
Enterohemorrhagic E. coli (EHEC) is a commonly occuring foodborne pathogen responsible for numerous multistate outbreaks in the US. 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 non-pathogenic 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. Based on 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 vivoIMPORTANCE Enterohemorrhagic E. coli (EHEC) is one of several foodborne pathogens that affect millions of people every year. Such pathogens infect the gut, preferring specific sites such as the gut-associated lymphoid tissue to initiate infection. Previous evidence has shown that norepinephrine, a stress hormone and the predominant neurotransmitter in the sympathetic nervous system that innervates the gut, exacerbates these infections by enhancing the virulence of the pathogens. Our research suggests metabolism of such host molecules by the gut microbiota may promote infections, offering promise of a new target for treatment of foodborne infections.

Publisher URL: https://www.ncbi.nlm.nih.gov/pubmed/28717028

DOI: PubMed:28717028

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