Conversion of Norepinephrine to 3,4-Dihdroxymandelic Acid in Escherichia coli Requires the QseBC Quorum-Sensing System and the FeaR Transcription Factor

Abstract

The detection of norepinephrine (NE) as a chemoattractant by strain K-12 requires the combined action of the TynA monoamine oxidase and the FeaB aromatic aldehyde dehydrogenase. The role of these enzymes is to convert NE into 3,4-dihydroxymandelic acid (DHMA), which is a potent chemoattractant sensed by the Tsr chemoreceptor. These two enzymes must be induced by prior exposure to NE, and cells that are exposed to NE for the first time initially show minimal chemotaxis toward it. The induction of TynA and FeaB requires the QseC quorum-sensing histidine kinase, and the signaling cascade requires new protein synthesis. Here, we demonstrate that the cognate response regulator for QseC, the transcription factor QseB, is also required for induction. The related quorum-sensing kinase QseE appears not to be part of the signaling pathway, but its cognate response regulator, QseF, which is also a substrate for phosphotransfer from QseC, plays a nonessential role. The promoter of the gene, which encodes a transcription factor that has been shown to be essential for the expression of and, has two predicted QseB-binding sites. One of these sites appears to be in an appropriate position to stimulate transcription from the P promoter of the gene. This study unites two well-known pathways: one for expression of genes regulated by catecholamines (QseBC) and one for expression of genes required for metabolism of aromatic amines (FeaR, TynA, and FeaB). This cross talk allows to convert the host-derived and chemotactically inert NE into the potent bacterial chemoattractant DHMA. The chemotaxis of K-12 to norepinephrine (NE) requires the conversion of NE to 3,4-dihydroxymandleic acid (DHMA), and DHMA is both an attractant and inducer of virulence gene expression for a pathogenic enterohemorrhagic (EHEC) strain. The induction of virulence by DHMA and NE requires QseC. The results described here show that the cognate response regulator for QseC, QseB, is also required for conversion of NE into DHMA. Production of DHMA requires induction of a pathway involved in the metabolism of aromatic amines. Thus, the QseBC sensory system provides a direct link between virulence and chemotaxis, suggesting that chemotaxis to host signaling molecules may require that those molecules are first metabolized by bacterial enzymes to generate the actual chemoattractant.

Chemotaxis of Escherichia coli to major hormones and polyamines present in human gut

“…They are therefore unlikely to form long-lived gradients that can be used for orientation in the intestine. Our results thus provide further evidence for the hypothesis that bacteria can specifically utilize host signals to detect their GI location [ 14 , 39 – 42 ].…”

“…The attractant response to low concentrations of NE is overall consistent with previous microfluidic measurements, although in those studies the chemotaxis towards low levels of NE was stronger and comparable to the chemotaxis towards amino acid attractants [ 39 , 40 ]. This response was shown to rely on the conversion of NE into DHMA, which could be induced by the NE-mediated signaling [ 40 – 42 ]. Indeed, we observed that the responses of the wild-type E. coli cells to NE and DHMA were similar, with DHMA eliciting a weak attractant response up to 50 µM but a strong repellent response at higher concentrations (Fig.…”

“…Moreover, both commensal E. coli K-12 and enterohemorrhagic E. coli (EHEC) can sense NE as a chemoattractant [ 39 – 41 ]. This response requires conversion of NE to 3,4-dihydroxymandelic acid (DHMA) by the monoamine oxidase TynA and the aromatic aldehyde dehydrogenase FeaB of E. coli , with DHMA then serving as the chemoattractant recognized by Tsr in the nanomolar concentration range [ 40 – 42 ]. These results indicate that hormone taxis might be common among enteric bacteria and not limited to pathogens, but the scope of this behavior remained unclear.…”

A genetic screen to identify factors affected by undecaprenyl phosphate recycling uncovers novel connections to morphogenesis inEscherichia coli

“…This means that (some) functions attributed to QseBC may actually be related to ancillary effects on the PG layer. To that end, QseB does not appear to regulate cell wall modifying genes (Sperandio et al, 2002, Pasupuleti et al, 2018, Gou et al, 2019, suggesting that QseB overactivation indirectly affects cell wall synthesis. In summary, we recommend that conclusions based on qseC mutants be reevaluated to account for indirect effects on the cell wall, ideally by comparing qseC to qseB mutants.…”

Escape band in Escherichia coli chemotaxis in opposing attractant and nutrient gradients

“…The escape band is a general phenomenon not limited by specific chemoattractants or receptors, and it should be physiologically relevant, as it enhances the fitness of the population by avoiding being trapped by nonmetabolizable or weakly metabolizable attractants, such as AI-2 in the biofilm (32,33) and DHMA for commensal bacteria in the gut microbiota (34,35). Indeed, our model showed that the overall population growth starving E.coli growing E.coli rate increases as the system changes from the no-band-forming regime to the band-forming regime (SI Appendix, Fig.…”