The Cu(II) Reductase RclA Protects <italic toggle="yes">Escherichia coli</italic> against the Combination of Hypochlorous Acid and Intracellular Copper

ABSTRACT Enterobacteria, including Escherichia coli, bloom to high levels in the gut during inflammation and strongly contribute to the pathology of inflammatory bowel diseases. To survive in the inflamed gut, E. coli must tolerate high levels of antimicrobial compounds produced by the immune system...

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Autores principales:	Rhea M. Derke, Alexander J. Barron, Caitlin E. Billiot, Ivis F. Chaple, Suzanne E. Lapi, Nichole A. Broderick, Michael J. Gray
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	copper hypochlorous acid oxidative stress reactive chlorine Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6bf5c5e91c114cd781897c7f542352d7
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spelling	oai:doaj.org-article:6bf5c5e91c114cd781897c7f542352d72021-11-15T16:19:09ZThe Cu(II) Reductase RclA Protects <italic toggle="yes">Escherichia coli</italic> against the Combination of Hypochlorous Acid and Intracellular Copper10.1128/mBio.01905-202150-7511https://doaj.org/article/6bf5c5e91c114cd781897c7f542352d72020-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01905-20https://doaj.org/toc/2150-7511ABSTRACT Enterobacteria, including Escherichia coli, bloom to high levels in the gut during inflammation and strongly contribute to the pathology of inflammatory bowel diseases. To survive in the inflamed gut, E. coli must tolerate high levels of antimicrobial compounds produced by the immune system, including toxic metals like copper and reactive chlorine oxidants such as hypochlorous acid (HOCl). Here, we show that extracellular copper is a potent detoxifier of HOCl and that the widely conserved bacterial HOCl resistance enzyme RclA, which catalyzes the reduction of copper(II) to copper(I), specifically protects E. coli against damage caused by the combination of HOCl and intracellular copper. E. coli lacking RclA was highly sensitive to HOCl when grown in the presence of copper and was defective in colonizing an animal host. Our results indicate that there is unexpected complexity in the interactions between antimicrobial toxins produced by innate immune cells and that bacterial copper status is a key determinant of HOCl resistance and suggest an important and previously unsuspected role for copper redox reactions during inflammation. IMPORTANCE During infection and inflammation, the innate immune system uses antimicrobial compounds to control bacterial populations. These include toxic metals, like copper, and reactive oxidants, including hypochlorous acid (HOCl). We have now found that RclA, a copper(II) reductase strongly induced by HOCl in proinflammatory Escherichia coli and found in many bacteria inhabiting epithelial surfaces, is required for bacteria to resist killing by the combination of intracellular copper and HOCl and plays an important role in colonization of an animal host. This finding indicates that copper redox chemistry plays a critical and previously underappreciated role in bacterial interactions with the innate immune system.Rhea M. DerkeAlexander J. BarronCaitlin E. BilliotIvis F. ChapleSuzanne E. LapiNichole A. BroderickMichael J. GrayAmerican Society for Microbiologyarticlecopperhypochlorous acidoxidative stressreactive chlorineMicrobiologyQR1-502ENmBio, Vol 11, Iss 5 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	copper hypochlorous acid oxidative stress reactive chlorine Microbiology QR1-502
spellingShingle	copper hypochlorous acid oxidative stress reactive chlorine Microbiology QR1-502 Rhea M. Derke Alexander J. Barron Caitlin E. Billiot Ivis F. Chaple Suzanne E. Lapi Nichole A. Broderick Michael J. Gray The Cu(II) Reductase RclA Protects <italic toggle="yes">Escherichia coli</italic> against the Combination of Hypochlorous Acid and Intracellular Copper
description	ABSTRACT Enterobacteria, including Escherichia coli, bloom to high levels in the gut during inflammation and strongly contribute to the pathology of inflammatory bowel diseases. To survive in the inflamed gut, E. coli must tolerate high levels of antimicrobial compounds produced by the immune system, including toxic metals like copper and reactive chlorine oxidants such as hypochlorous acid (HOCl). Here, we show that extracellular copper is a potent detoxifier of HOCl and that the widely conserved bacterial HOCl resistance enzyme RclA, which catalyzes the reduction of copper(II) to copper(I), specifically protects E. coli against damage caused by the combination of HOCl and intracellular copper. E. coli lacking RclA was highly sensitive to HOCl when grown in the presence of copper and was defective in colonizing an animal host. Our results indicate that there is unexpected complexity in the interactions between antimicrobial toxins produced by innate immune cells and that bacterial copper status is a key determinant of HOCl resistance and suggest an important and previously unsuspected role for copper redox reactions during inflammation. IMPORTANCE During infection and inflammation, the innate immune system uses antimicrobial compounds to control bacterial populations. These include toxic metals, like copper, and reactive oxidants, including hypochlorous acid (HOCl). We have now found that RclA, a copper(II) reductase strongly induced by HOCl in proinflammatory Escherichia coli and found in many bacteria inhabiting epithelial surfaces, is required for bacteria to resist killing by the combination of intracellular copper and HOCl and plays an important role in colonization of an animal host. This finding indicates that copper redox chemistry plays a critical and previously underappreciated role in bacterial interactions with the innate immune system.
format	article
author	Rhea M. Derke Alexander J. Barron Caitlin E. Billiot Ivis F. Chaple Suzanne E. Lapi Nichole A. Broderick Michael J. Gray
author_facet	Rhea M. Derke Alexander J. Barron Caitlin E. Billiot Ivis F. Chaple Suzanne E. Lapi Nichole A. Broderick Michael J. Gray
author_sort	Rhea M. Derke
title	The Cu(II) Reductase RclA Protects <italic toggle="yes">Escherichia coli</italic> against the Combination of Hypochlorous Acid and Intracellular Copper
title_short	The Cu(II) Reductase RclA Protects <italic toggle="yes">Escherichia coli</italic> against the Combination of Hypochlorous Acid and Intracellular Copper
title_full	The Cu(II) Reductase RclA Protects <italic toggle="yes">Escherichia coli</italic> against the Combination of Hypochlorous Acid and Intracellular Copper
title_fullStr	The Cu(II) Reductase RclA Protects <italic toggle="yes">Escherichia coli</italic> against the Combination of Hypochlorous Acid and Intracellular Copper
title_full_unstemmed	The Cu(II) Reductase RclA Protects <italic toggle="yes">Escherichia coli</italic> against the Combination of Hypochlorous Acid and Intracellular Copper
title_sort	cu(ii) reductase rcla protects <italic toggle="yes">escherichia coli</italic> against the combination of hypochlorous acid and intracellular copper
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/6bf5c5e91c114cd781897c7f542352d7
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The Cu(II) Reductase RclA Protects <italic toggle="yes">Escherichia coli</italic> against the Combination of Hypochlorous Acid and Intracellular Copper

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