Bleach Activates a Redox-Regulated Chaperone by Oxidative Protein Unfolding

Hypochlorous acid (HOCl), the active ingredient in household bleach, is an effective antimicrobial produced by the mammalian host defense to kill invading microorganisms. Despite the widespread use of HOCl, surprisingly little is known about its mode of action. In this study, we demonstrate that low...

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Bibliographic Details
Published in:	Cell Vol. 135; no. 4; pp. 691 - 701
Main Authors:	Winter, J., Ilbert, M., Graf, P.C.F., Özcelik, D., Jakob, U.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 14-11-2008
Subjects:	CELLBIO Disulfides Escherichia coli Escherichia coli - metabolism Escherichia coli Proteins - metabolism Heat-Shock Proteins - metabolism HUMDISEASE Hypochlorous Acid - pharmacology Models, Biological Molecular Chaperones - metabolism Molecular Conformation Oxidation-Reduction Oxygen - metabolism Protein Denaturation Protein Structure, Tertiary Reactive Oxygen Species Substrate Specificity Sulfhydryl Compounds - chemistry Temperature CELLBIO HUMDISEASE
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Summary:	Hypochlorous acid (HOCl), the active ingredient in household bleach, is an effective antimicrobial produced by the mammalian host defense to kill invading microorganisms. Despite the widespread use of HOCl, surprisingly little is known about its mode of action. In this study, we demonstrate that low molar ratios of HOCl to protein cause oxidative protein unfolding in vitro and target thermolabile proteins for irreversible aggregation in vivo. As a defense mechanism, bacteria use the redox-regulated chaperone Hsp33, which responds to bleach treatment with the reversible oxidative unfolding of its C-terminal redox switch domain. HOCl-mediated unfolding turns inactive Hsp33 into a highly active chaperone holdase, which protects essential Escherichia coli proteins against HOCl-induced aggregation and increases bacterial HOCl resistance. Our results substantially improve our molecular understanding about HOCl's functional mechanism. They suggest that the antimicrobial effects of bleach are largely based on HOCl's ability to cause aggregation of essential bacterial proteins.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Both authors contributed equally to this work present address: Institut für Biotechnologie, Department Chemie, Technische Universität München, Garching, Germany present address: Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, MD 20910-7500
ISSN:	0092-8674 1097-4172
DOI:	10.1016/j.cell.2008.09.024