Verapamil, a Ca2+ channel inhibitor acts as a local anesthetic and induces the sigma E dependent extra-cytoplasmic stress response in E. coli.
Verapamil is used clinically as a Ca(2+) channel inhibitor for the treatment of various disorders such as angina, hypertension and cardiac arrhythmia. Here we study the effect of verapamil on the bacterium Escherichia coli. The drug was shown to inhibit cell division at growth sub inhibitory concentrations, independently of the SOS response. We show verapamil is a membrane active drug, with similar effects to dibucaine, a local anesthetic. Thus, both verapamil and dibucaine abolish the proton motive force and decrease the intracellular ATP concentration. This is accompanied by induction of degP expression, as a result of the activation of the RpoE (SigmaE) extra-cytoplasmic stress response, and activation of the psp operon. Such effects of verapamil, as a membrane active compound, could explain its general toxicity in eukaryotic cells.
Andersen
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CL
Institut de Génétique et Microbiologie, UMR 8621, Université Paris-Sud (XI), Bâtiment 400, 91405 Orsay cedex, France.
Holland
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IB
Jacq
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D000779:Anesthetics, Local / Q000494:pharmacology; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003992:Dibucaine / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000096:biosynthesis; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D008564:Membrane Potentials / Q000187:drug effects; D033903:Periplasmic Proteins / Q000096:biosynthesis; D012697:Serine Endopeptidases / Q000096:biosynthesis; D012808:Sigma Factor / Q000096:biosynthesis*; D014157:Transcription Factors / Q000096:biosynthesis*; D014700:Verapamil / Q000494:pharmacology*
D000779:Anesthetics, Local; D001426:Bacterial Proteins; D002121:Calcium Channel Blockers; D029968:Escherichia coli Proteins; D006360:Heat-Shock Proteins; D033903:Periplasmic Proteins; D012808:Sigma Factor; D014157:Transcription Factors; C069816:phage shock protein, Bacteria; C063202:sporulation-specific sigma factors; C085504:CpxR protein, Bacteria; D014700:Verapamil; C061682:DegP protease; D012697:Serine Endopeptidases; D003992:Dibucaine