Eukaryotic catecholamine hormones influence the chemotactic control of Vibrio campbellii by binding to the coupling protein CheW.

Eukaryotic catecholamine hormones influence the chemotactic control of Vibrio campbellii by binding to the coupling protein CheW.
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DOI:
10.1073/pnas.2118227119
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发表时间:
2022-03-08
影响因子:
11.1
通讯作者:
Jung K
Jung K
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Weigert Muñoz A;Hoyer E;Schumacher K;Grognot M;Taute KM;Hacker SM;Sieber SA;Jung K

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Host-emitted stress hormones significantly influence the growth and behavior of various bacterial species; however, their cellular targets have so far remained elusive. Here, we used customized probes and quantitative proteomics to identify the target of epinephrine and the α-adrenoceptor agonist phenylephrine in live cells of the aquatic pathogen Vibrio campbellii. Consequently, we have discovered the coupling protein CheW, which is in the center of the chemotaxis signaling network, as a target of both molecules. We not only demonstrate direct ligand binding to CheW but also elucidate how this affects chemotactic control. These findings are pivotal for further research on hormone-specific effects on bacterial behavior. In addition to their well-known role as stress-associated catecholamine hormones in animals and humans, epinephrine (EPI) and norepinephrine (NE) act as interkingdom signals between eukaryotic hosts and bacteria. However, the molecular basis of their effects on bacteria is not well understood. In initial phenotypic studies utilizing Vibrio campbellii as a model organism, we characterized the bipartite mode of action of catecholamines, which consists of promotion of growth under iron limitation and enhanced colony expansion on soft agar. In order to identify the molecular targets of the hormones, we designed and synthesized tailored probes for chemical proteomic studies. As the catechol group in EPI and NE acts as an iron chelator and is prone to form a reactive quinone moiety, we devised a photoprobe based on the adrenergic agonist phenylephrine (PE), which solely influenced colony expansion. Using this probe, we identified CheW, located at the core of the chemotaxis signaling network, as a major target. In vitro studies confirmed that EPI, NE, PE, and labetalol, a clinically applied antagonist, bind to purified CheW with affinity constants in the submicromolar range. In line with these findings, exposure of V. campbellii to these adrenergic agonists affects the chemotactic control of the bacterium. This study highlights an effect of eukaryotic signaling molecules on bacterial motility.
DOI: 10.1038/s41586-021-03819-2
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