Analysis of the organic hydroperoxide response of Chromobacterium violaceum reveals that OhrR is a cys-based redox sensor regulated by thioredoxin.

Organic hydroperoxides are oxidants generated during bacterial-host interactions. Here, we demonstrate that the peroxidase OhrA and its negative regulator OhrR comprise a major pathway for sensing and detoxifying organic hydroperoxides in the opportunistic pathogen Chromobacterium violaceum. Initial...

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Autores principales:	José F da Silva Neto, Caroline C Negretto, Luis E S Netto
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0f6627d32cf3428c803b07ae718bbf6c
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spelling	oai:doaj.org-article:0f6627d32cf3428c803b07ae718bbf6c2021-11-18T08:12:21ZAnalysis of the organic hydroperoxide response of Chromobacterium violaceum reveals that OhrR is a cys-based redox sensor regulated by thioredoxin.1932-620310.1371/journal.pone.0047090https://doaj.org/article/0f6627d32cf3428c803b07ae718bbf6c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23071722/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Organic hydroperoxides are oxidants generated during bacterial-host interactions. Here, we demonstrate that the peroxidase OhrA and its negative regulator OhrR comprise a major pathway for sensing and detoxifying organic hydroperoxides in the opportunistic pathogen Chromobacterium violaceum. Initially, we found that an ohrA mutant was hypersensitive to organic hydroperoxides and that it displayed a low efficiency for decomposing these molecules. Expression of ohrA and ohrR was specifically induced by organic hydroperoxides. These genes were expressed as monocistronic transcripts and also as a bicistronic ohrR-ohrA mRNA, generating the abundantly detected ohrA mRNA and the barely detected ohrR transcript. The bicistronic transcript appears to be processed. OhrR repressed both the ohrA and ohrR genes by binding directly to inverted repeat sequences within their promoters in a redox-dependent manner. Site-directed mutagenesis of each of the four OhrR cysteine residues indicated that the conserved Cys21 is critical to organic hydroperoxide sensing, whereas Cys126 is required for disulfide bond formation. Taken together, these phenotypic, genetic and biochemical data indicate that the response of C. violaceum to organic hydroperoxides is mediated by OhrA and OhrR. Finally, we demonstrated that oxidized OhrR, inactivated by intermolecular disulfide bond formation, is specifically regenerated via thiol-disulfide exchange by thioredoxin (but not other thiol reducing agents such as glutaredoxin, glutathione and lipoamide), providing a physiological reducing system for this thiol-based redox switch.José F da Silva NetoCaroline C NegrettoLuis E S NettoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 10, p e47090 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q José F da Silva Neto Caroline C Negretto Luis E S Netto Analysis of the organic hydroperoxide response of Chromobacterium violaceum reveals that OhrR is a cys-based redox sensor regulated by thioredoxin.
description	Organic hydroperoxides are oxidants generated during bacterial-host interactions. Here, we demonstrate that the peroxidase OhrA and its negative regulator OhrR comprise a major pathway for sensing and detoxifying organic hydroperoxides in the opportunistic pathogen Chromobacterium violaceum. Initially, we found that an ohrA mutant was hypersensitive to organic hydroperoxides and that it displayed a low efficiency for decomposing these molecules. Expression of ohrA and ohrR was specifically induced by organic hydroperoxides. These genes were expressed as monocistronic transcripts and also as a bicistronic ohrR-ohrA mRNA, generating the abundantly detected ohrA mRNA and the barely detected ohrR transcript. The bicistronic transcript appears to be processed. OhrR repressed both the ohrA and ohrR genes by binding directly to inverted repeat sequences within their promoters in a redox-dependent manner. Site-directed mutagenesis of each of the four OhrR cysteine residues indicated that the conserved Cys21 is critical to organic hydroperoxide sensing, whereas Cys126 is required for disulfide bond formation. Taken together, these phenotypic, genetic and biochemical data indicate that the response of C. violaceum to organic hydroperoxides is mediated by OhrA and OhrR. Finally, we demonstrated that oxidized OhrR, inactivated by intermolecular disulfide bond formation, is specifically regenerated via thiol-disulfide exchange by thioredoxin (but not other thiol reducing agents such as glutaredoxin, glutathione and lipoamide), providing a physiological reducing system for this thiol-based redox switch.
format	article
author	José F da Silva Neto Caroline C Negretto Luis E S Netto
author_facet	José F da Silva Neto Caroline C Negretto Luis E S Netto
author_sort	José F da Silva Neto
title	Analysis of the organic hydroperoxide response of Chromobacterium violaceum reveals that OhrR is a cys-based redox sensor regulated by thioredoxin.
title_short	Analysis of the organic hydroperoxide response of Chromobacterium violaceum reveals that OhrR is a cys-based redox sensor regulated by thioredoxin.
title_full	Analysis of the organic hydroperoxide response of Chromobacterium violaceum reveals that OhrR is a cys-based redox sensor regulated by thioredoxin.
title_fullStr	Analysis of the organic hydroperoxide response of Chromobacterium violaceum reveals that OhrR is a cys-based redox sensor regulated by thioredoxin.
title_full_unstemmed	Analysis of the organic hydroperoxide response of Chromobacterium violaceum reveals that OhrR is a cys-based redox sensor regulated by thioredoxin.
title_sort	analysis of the organic hydroperoxide response of chromobacterium violaceum reveals that ohrr is a cys-based redox sensor regulated by thioredoxin.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/0f6627d32cf3428c803b07ae718bbf6c
work_keys_str_mv	AT josefdasilvaneto analysisoftheorganichydroperoxideresponseofchromobacteriumviolaceumrevealsthatohrrisacysbasedredoxsensorregulatedbythioredoxin AT carolinecnegretto analysisoftheorganichydroperoxideresponseofchromobacteriumviolaceumrevealsthatohrrisacysbasedredoxsensorregulatedbythioredoxin AT luisesnetto analysisoftheorganichydroperoxideresponseofchromobacteriumviolaceumrevealsthatohrrisacysbasedredoxsensorregulatedbythioredoxin
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Analysis of the organic hydroperoxide response of Chromobacterium violaceum reveals that OhrR is a cys-based redox sensor regulated by thioredoxin.

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