Genome-Wide Characterization of the Fur Regulatory Network Reveals a Link between Catechol Degradation and Bacillibactin Metabolism in <named-content content-type="genus-species">Bacillus subtilis</named-content>

ABSTRACT The ferric uptake regulator (Fur) is the global iron biosensor in many bacteria. Fur functions as an iron-dependent transcriptional repressor for most of its regulated genes. There are a few examples where holo-Fur activates transcription, either directly or indirectly. Recent studies sugge...

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Autores principales:	Hualiang Pi, John D. Helmann
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Fur regulon ChIP-seq catechol degradation bacillibactin metabolism bacillibactin degradation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/683f97c6f78844f8b10f2015ea59fa11
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spelling	oai:doaj.org-article:683f97c6f78844f8b10f2015ea59fa112021-11-15T15:58:20ZGenome-Wide Characterization of the Fur Regulatory Network Reveals a Link between Catechol Degradation and Bacillibactin Metabolism in <named-content content-type="genus-species">Bacillus subtilis</named-content>10.1128/mBio.01451-182150-7511https://doaj.org/article/683f97c6f78844f8b10f2015ea59fa112018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01451-18https://doaj.org/toc/2150-7511ABSTRACT The ferric uptake regulator (Fur) is the global iron biosensor in many bacteria. Fur functions as an iron-dependent transcriptional repressor for most of its regulated genes. There are a few examples where holo-Fur activates transcription, either directly or indirectly. Recent studies suggest that apo-Fur might also act as a positive regulator and that, besides iron metabolism, the Fur regulon might encompass other biological processes such as DNA synthesis, energy metabolism, and biofilm formation. Here, we obtained a genomic view of the Fur regulatory network in Bacillus subtilis using chromatin immunoprecipitation sequencing (ChIP-seq). Besides the known Fur target sites, 70 putative DNA binding sites were identified, and the vast majority had higher occupancy under iron-sufficient conditions. Among the new sites detected, a Fur binding site in the promoter region of the catDE operon is of particular interest. This operon, encoding catechol 2,3-dioxygenase, is critical for catechol degradation and is under negative regulation of CatR and YodB. These three repressors (Fur, CatR, and YodB) function cooperatively to regulate the transcription of catDE, with Fur functioning as a sensor of iron limitation and CatR as the major sensor of catechol stress. Genetic analysis suggests that CatDE is involved in metabolism of the catecholate siderophore bacillibactin, particularly when bacillibactin is constitutively produced and accumulates intracellularly, potentially generating endogenous toxic catechol derivatives. This study documents a role for catechol degradation in bacillibactin metabolism and provides evidence that catechol 2,3-dioxygenase can detoxify endogenously produced catechol substrates in addition to its more widely studied role in biodegradation of environmental aromatic compounds and pollutants. IMPORTANCE Many bacteria synthesize high-affinity iron chelators (siderophores). Siderophore-mediated iron acquisition is an efficient and widely utilized strategy for bacteria to meet their cellular iron requirements. One prominent class of siderophores uses catecholate groups to chelate iron. B. subtilis bacillibactin, structurally similar to enterobactin (made by enteric bacteria), is a triscatecholate siderophore that is hydrolyzed to monomeric units after import to release iron. However, the ultimate fates of these catechol compounds and their potential toxicities have not been defined previously. We performed genome-wide identification of Fur binding sites in vivo and uncovered a connection between catechol degradation and bacillibactin metabolism in B. subtilis. Besides its role in the detoxification of environmental catechols, the catechol 2,3-dioxygenase encoded by catDE also protects cells from intoxication by endogenous bacillibactin-derived catechol metabolites under iron-limited conditions. These findings shed light on the degradation pathway and precursor recycling of the catecholate siderophores.Hualiang PiJohn D. HelmannAmerican Society for MicrobiologyarticleFur regulonChIP-seqcatechol degradationbacillibactin metabolismbacillibactin degradationMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Fur regulon ChIP-seq catechol degradation bacillibactin metabolism bacillibactin degradation Microbiology QR1-502
spellingShingle	Fur regulon ChIP-seq catechol degradation bacillibactin metabolism bacillibactin degradation Microbiology QR1-502 Hualiang Pi John D. Helmann Genome-Wide Characterization of the Fur Regulatory Network Reveals a Link between Catechol Degradation and Bacillibactin Metabolism in <named-content content-type="genus-species">Bacillus subtilis</named-content>
description	ABSTRACT The ferric uptake regulator (Fur) is the global iron biosensor in many bacteria. Fur functions as an iron-dependent transcriptional repressor for most of its regulated genes. There are a few examples where holo-Fur activates transcription, either directly or indirectly. Recent studies suggest that apo-Fur might also act as a positive regulator and that, besides iron metabolism, the Fur regulon might encompass other biological processes such as DNA synthesis, energy metabolism, and biofilm formation. Here, we obtained a genomic view of the Fur regulatory network in Bacillus subtilis using chromatin immunoprecipitation sequencing (ChIP-seq). Besides the known Fur target sites, 70 putative DNA binding sites were identified, and the vast majority had higher occupancy under iron-sufficient conditions. Among the new sites detected, a Fur binding site in the promoter region of the catDE operon is of particular interest. This operon, encoding catechol 2,3-dioxygenase, is critical for catechol degradation and is under negative regulation of CatR and YodB. These three repressors (Fur, CatR, and YodB) function cooperatively to regulate the transcription of catDE, with Fur functioning as a sensor of iron limitation and CatR as the major sensor of catechol stress. Genetic analysis suggests that CatDE is involved in metabolism of the catecholate siderophore bacillibactin, particularly when bacillibactin is constitutively produced and accumulates intracellularly, potentially generating endogenous toxic catechol derivatives. This study documents a role for catechol degradation in bacillibactin metabolism and provides evidence that catechol 2,3-dioxygenase can detoxify endogenously produced catechol substrates in addition to its more widely studied role in biodegradation of environmental aromatic compounds and pollutants. IMPORTANCE Many bacteria synthesize high-affinity iron chelators (siderophores). Siderophore-mediated iron acquisition is an efficient and widely utilized strategy for bacteria to meet their cellular iron requirements. One prominent class of siderophores uses catecholate groups to chelate iron. B. subtilis bacillibactin, structurally similar to enterobactin (made by enteric bacteria), is a triscatecholate siderophore that is hydrolyzed to monomeric units after import to release iron. However, the ultimate fates of these catechol compounds and their potential toxicities have not been defined previously. We performed genome-wide identification of Fur binding sites in vivo and uncovered a connection between catechol degradation and bacillibactin metabolism in B. subtilis. Besides its role in the detoxification of environmental catechols, the catechol 2,3-dioxygenase encoded by catDE also protects cells from intoxication by endogenous bacillibactin-derived catechol metabolites under iron-limited conditions. These findings shed light on the degradation pathway and precursor recycling of the catecholate siderophores.
format	article
author	Hualiang Pi John D. Helmann
author_facet	Hualiang Pi John D. Helmann
author_sort	Hualiang Pi
title	Genome-Wide Characterization of the Fur Regulatory Network Reveals a Link between Catechol Degradation and Bacillibactin Metabolism in <named-content content-type="genus-species">Bacillus subtilis</named-content>
title_short	Genome-Wide Characterization of the Fur Regulatory Network Reveals a Link between Catechol Degradation and Bacillibactin Metabolism in <named-content content-type="genus-species">Bacillus subtilis</named-content>
title_full	Genome-Wide Characterization of the Fur Regulatory Network Reveals a Link between Catechol Degradation and Bacillibactin Metabolism in <named-content content-type="genus-species">Bacillus subtilis</named-content>
title_fullStr	Genome-Wide Characterization of the Fur Regulatory Network Reveals a Link between Catechol Degradation and Bacillibactin Metabolism in <named-content content-type="genus-species">Bacillus subtilis</named-content>
title_full_unstemmed	Genome-Wide Characterization of the Fur Regulatory Network Reveals a Link between Catechol Degradation and Bacillibactin Metabolism in <named-content content-type="genus-species">Bacillus subtilis</named-content>
title_sort	genome-wide characterization of the fur regulatory network reveals a link between catechol degradation and bacillibactin metabolism in <named-content content-type="genus-species">bacillus subtilis</named-content>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/683f97c6f78844f8b10f2015ea59fa11
work_keys_str_mv	AT hualiangpi genomewidecharacterizationofthefurregulatorynetworkrevealsalinkbetweencatecholdegradationandbacillibactinmetabolisminnamedcontentcontenttypegenusspeciesbacillussubtilisnamedcontent AT johndhelmann genomewidecharacterizationofthefurregulatorynetworkrevealsalinkbetweencatecholdegradationandbacillibactinmetabolisminnamedcontentcontenttypegenusspeciesbacillussubtilisnamedcontent
_version_	1718427032512102400

Genome-Wide Characterization of the Fur Regulatory Network Reveals a Link between Catechol Degradation and Bacillibactin Metabolism in <named-content content-type="genus-species">Bacillus subtilis</named-content>

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