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 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.
Winter
J
J
Department of Molecular, University of Michigan, Ann Arbor, MI 48109, USA.
Ilbert
M
M
Graf
P C F
PC
Ozcelik
D
D
Jakob
U
U
D004220:Disulfides; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D006997:Hypochlorous Acid / Q000494:pharmacology*; D008954:Models, Biological; D018832:Molecular Chaperones / Q000378:metabolism; D008968:Molecular Conformation; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D011489:Protein Denaturation; D017434:Protein Structure, Tertiary; D017382:Reactive Oxygen Species; D013379:Substrate Specificity; D013438:Sulfhydryl Compounds / Q000737:chemistry; D013696:Temperature
D004220:Disulfides; D029968:Escherichia coli Proteins; C492165:HSP33 protein, E coli; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D006997:Hypochlorous Acid; D010100:Oxygen