Proteomics

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


ABSTRACT: 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. 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 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 on soft agar. 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, as well as labetalol, a clinically applied antagonist, bind to purified CheW with affinity constants in the sub-micromolar range. In line with these findings, exposure of V. campbellii to these adrenergic agonists affects the chemotactic control of the bacterium. This study highlights a previously unknown effect of eukaryotic signaling molecules on bacterial motility.

INSTRUMENT(S): Orbitrap Fusion, Q Exactive

ORGANISM(S): Bacteria Vibrio Campbellii (strain Atcc Baa-1116 / Bb120)

SUBMITTER: Angela Weigert Muñoz  

LAB HEAD: Stephan Axel Sieber

PROVIDER: PXD029119 | Pride | 2022-04-04

REPOSITORIES: Pride

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

Weigert Muñoz Angela A   Hoyer Elisabeth E   Schumacher Kilian K   Grognot Marianne M   Taute Katja M KM   Hacker Stephan M SM   Sieber Stephan A SA   Jung Kirsten K  

Proceedings of the National Academy of Sciences of the United States of America 20220301 10


SignificanceHost-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 <i>Vibrio campbellii</i>. Consequently, we have discovered the coupling protein CheW, which is in the center of the chemotaxis signaling n  ...[more]

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