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

Abstract

SummaryThe QseBC 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, QseBC 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 QseBC 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 QseBC signaling may identify additional differences in QseBC function and inform further development of new therapeutics to control microbial infections.

Adaptation to host in Vibrio vulnificus, a zoonotic pathogen that causes septicemia in fish and humans

“…in iron-overloaded media in response to catecolamines (Weigel et al, 2015) as well as an activator of motility (Weigel and Demuth, 2016), a phenotype that is induced in iron-overloaded human serum (Table 3 and Supporting Information Fig. S2B).…”

Structure and Function of the Fecal Microbiota in Diarrheic Neonatal Piglets

“…Defects in the type III secretion system render a bacterium non-pathogenic (Gong et al, 2010); the QseBC two-component system was associated with bacterial quorum sensing and virulence factors expression (Weigel and Demuth, 2015). We observed that decreased gene relative abundances for the type III secretion system and the QseBC two-component system were mainly assigned to Escherichia , which exerts a barrier effect against enteropathogens (Hudault et al, 2001), and are responsible for providing vitamin K2 (Meganathan, 2001), suggesting a depleted beneficial metabolism from Escherichia in diarrheic piglets.…”

Function of the enterobactin operon of A. actinomycetemcomitans in the presence of catecholmines and iron.

“…This activation leads to increased expression of genes responsible for biofilm growth, the expression of flagella and motility as well as other virulence genes [21]. Furthermore, QseBC expressed by H. influenzae responds to ferrous iron, but not catecholamines [23].…”

“…There is also evidence that the two-component system QseBC is activated in the presence of iron-catecholamine complexes, leading to an induction of genes responsible for anaerobic metabolism and respiration and a down regulation in genes encoding iron acquisition [21]. This is possibly a result of the bacteria sensing an iron rich environment and spends less energy in trying to bring in large amounts of iron.…”