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Summary  The Qse BC  two‐component system ( TCS ) is associated with quorum sensing and functions as a global regulator of virulence. Based on sequence similarity within the sensor domain and conservation of an acidic motif essential for signal recognition, Qse BC  is primarily distributed in the  Enterobacteriaceae  and  Pasteurellaceae . In  Escherichia coli , QseC responds to autoinducer‐3 and/or epinephrine/norepinephrine. Binding of epinephrine/norepinephrine is inhibited by adrenergic antagonists; hence QseC functions as a bacterial adrenergic receptor.  Aggregatibacter actinomycetemcomitans  QseC is activated by a combination of epinephrine/norepinephrine and iron, whereas only iron activates the  Haemophilus influenzae  sensor. QseC phosphorylates QseB but there is growing evidence that QseB is activated by non‐cognate sensors and regulated by dephosphorylation via QseC. Interestingly, the Qse BC  signaling cascades and regulons differ significantly. In enterohemorrhagic  E. coli , QseC induces expression of a second adrenergic  TCS  and phosphorylates two non‐cognate response regulators, each of which induces specific sets of virulence genes. This signaling pathway integrates with other regulatory mechanisms mediated by transcriptional regulators QseA and QseD and a fucose‐sensing  TCS  and likely controls the level and timing of virulence gene expression. In contrast,  A. actinomycetemcomitans  QseC signals through QseB to regulate genes involved in anaerobic metabolism and energy production, which may prime cellular metabolism for growth in an anaerobic host niche. QseC represents a novel target for therapeutic intervention and small molecule inhibitors already show promise as broad‐spectrum antimicrobials. Further characterization of Qse BC  signaling may identify additional differences in Qse BC  function and inform further development of new therapeutics to control microbial infections.

Qse BC , a two‐component bacterial adrenergic receptor and global regulator of virulence in Enterobacteriaceae and Pasteurellaceae