The QseC sensor kinase: A bacterial adrenergic receptor

Abstract

Quorum sensing is a cell-to-cell signaling mechanism in which bacteria respond to hormone-like molecules called autoinducers (AIs). The AI-3 quorum-sensing system is also involved in interkingdom signaling with the eukaryotic hormones epinephrine͞ norepinephrine. This signaling activates transcription of virulence genes in enterohemorrhagic Escherichia coli O157:H7. However, this signaling system has never been shown to be involved in virulence in vivo, and the bacterial receptor for these signals had not been identified. Here, we show that the QseC sensor kinase is a bacterial receptor for the host epinephrine͞norepinephrine and the AI-3 produced by the gastrointestinal microbial flora. We also found that an ␣-adrenergic antagonist can specifically block the QseC response to these signals. Furthermore, we demonstrated that a qseC mutant is attenuated for virulence in a rabbit animal model, underscoring the importance of this signaling system in virulence in vivo. Finally, an in silico search found that the periplasmic sensing domain of QseC is conserved among several bacterial species. Thus, QseC is a bacterial adrenergic receptor that activates virulence genes in response to interkingdom cross-signaling. We anticipate that these studies will be a starting point in understanding bacterial-host hormone signaling at the biochemical level. Given the role that this system plays in bacterial virulence, further characterization of this unique signaling mechanism may be important for developing novel classes of antimicrobials.AI-3 ͉ enterohemorrhagic Escherichia coli ͉ epinephrine ͉ quorum sensing ͉ two-component systems

Quorum sensing in bacterial virulence

“…Biochemical studies have revealed not only that the expression of QseC is activated by AI-3 but also that this sensor kinase is the receptor for the AI (Clarke et al, 2006). Interestingly, QseC also functions as the receptor for the host catecholamine hormones epinephrine and norepinephrine, indicating that small molecule signalling pathways in eukaryotes and bacteria can intertwine (Clarke et al, 2006). Addition of AI-3 or catecholamines to QseC-containing liposomes resulted in an increased phosphorylation of this protein.…”

“…Mutant analyses have led to the conclusion that AI-3 affects gene expression through QseBC, since this AI activates qseBC expression and a qseC mutant is unable to regulate motility in response to AI-3 (Sperandio et al, 2003). Biochemical studies have revealed not only that the expression of QseC is activated by AI-3 but also that this sensor kinase is the receptor for the AI (Clarke et al, 2006). Interestingly, QseC also functions as the receptor for the host catecholamine hormones epinephrine and norepinephrine, indicating that small molecule signalling pathways in eukaryotes and bacteria can intertwine (Clarke et al, 2006).…”

“…Additionally, the activation of QseC resulted in phosphorylation of QseB, showing that QseB acts as the cognate response regulator in this system (Clarke et al, 2006). Besides QseBC, multiple regulators are involved in the control of virulence gene expression.…”

“…To test this hypothesis, Clarke et al (2006) used a rabbit model of infection to show that a qseC mutant is attenuated during infection of rabbits, confirming the role of quorum sensing in E. coli virulence. Additionally, qseC has proved important for bacterial virulence in both Salmonella enterica serovar Typhimurium and Francisella tularensis (Rasko et al, 2008).…”

Molecular insights into farm animal and zoonoticSalmonellainfections

“…An alternative hypothesis, not exclusive to that above, is that Salmonella senses and responds to NA using an orthologue of the Escherichia coli O157 : H7 adrenergic sensor kinase QseC (also known as PreB, YgiY and STM3178 in S. Typhimurium). Escherichia coli O157 : H7 QseC is an inner membrane sensor kinase that autophosphorylates on binding NA or adrenaline, then transfers the phosphate moiety to its cognate response-regulator QseB, thereby modulating the transcription of genes under its control (Clarke et al 2006). It is not yet known if S. Typhimurium QseC binds NA and activates QseB as a consequence.…”