Critical Role of Zur and SmtB in Zinc Homeostasis of <named-content content-type="genus-species">Mycobacterium smegmatis</named-content>

ABSTRACT Zinc homeostasis is crucial for bacterial cells, since imbalances affect viability. However, in mycobacteria, knowledge of zinc metabolism is incomplete. Mycobacterium smegmatis (MSMEG) is an environmental, nonpathogenic Mycobacterium that is widely used as a model organism to study mycobac...

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Autores principales:	Elke Goethe, Kristin Laarmann, Janita Lührs, Michael Jarek, Jochen Meens, Astrid Lewin, Ralph Goethe
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	zinc homeostasis zinc transporter zinc starvation zinc excess Zur regulon SmtB regulon Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/78642ba8ad9444bf9e83df48c176ae47
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spelling	oai:doaj.org-article:78642ba8ad9444bf9e83df48c176ae472021-12-02T18:15:46ZCritical Role of Zur and SmtB in Zinc Homeostasis of <named-content content-type="genus-species">Mycobacterium smegmatis</named-content>10.1128/mSystems.00880-192379-5077https://doaj.org/article/78642ba8ad9444bf9e83df48c176ae472020-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00880-19https://doaj.org/toc/2379-5077ABSTRACT Zinc homeostasis is crucial for bacterial cells, since imbalances affect viability. However, in mycobacteria, knowledge of zinc metabolism is incomplete. Mycobacterium smegmatis (MSMEG) is an environmental, nonpathogenic Mycobacterium that is widely used as a model organism to study mycobacterial metabolism and pathogenicity. How MSMEG maintains zinc homeostasis is largely unknown. SmtB and Zur are important regulators of bacterial zinc metabolism. In mycobacteria, these regulators are encoded by an operon, whereas in other bacterial species, SmtB and Zur are encoded on separate loci. Here, we show that the smtB-zur operon is consistently present within the genus Mycobacterium but otherwise found only in Nocardia, Saccharothrix, and Corynebacterium diphtheriae. By RNA deep sequencing, we determined the Zur and SmtB regulons of MSMEG and compared them with transcriptional responses after zinc starvation or excess. We found an exceptional genomic clustering of genes whose expression was strongly induced by zur deletion and zinc starvation. These genes encoded zinc importers such as ZnuABC and three additional putative zinc transporters, including the porin MspD, as well as alternative ribosomal proteins. In contrast, only a few genes were affected by deletion of smtB and zinc excess. The zinc exporter ZitA was most prominently regulated by SmtB. Moreover, transcriptional analyses in combination with promoter and chromatin immunoprecipitation assays revealed a special regulation of the smtB-zur operon itself: an apparently zinc-independent, constitutive expression of smtB-zur resulted from sensitive coregulation by both SmtB and Zur. Overall, our data revealed yet unknown peculiarities of mycobacterial zinc homeostasis. IMPORTANCE Zinc is crucial for many biological processes, as it is an essential cofactor of enzymes and a structural component of regulatory and DNA binding proteins. Hence, all living cells require zinc to maintain constant intracellular levels. However, in excess, zinc is toxic. Therefore, cellular zinc homeostasis needs to be tightly controlled. In bacteria, this is achieved by transcriptional regulators whose activity is mediated via zinc-dependent conformational changes promoting or preventing their binding to DNA. SmtB and Zur are important antagonistically acting bacterial regulators in mycobacteria. They sense changes in zinc concentrations in the femtomolar range and regulate transcription of genes for zinc acquisition, storage, and export. Here, we analyzed the role of SmtB and Zur in zinc homeostasis in Mycobacterium smegmatis. Our results revealed novel insights into the transcriptional processes of zinc homeostasis in mycobacteria and their regulation.Elke GoetheKristin LaarmannJanita LührsMichael JarekJochen MeensAstrid LewinRalph GoetheAmerican Society for Microbiologyarticlezinc homeostasiszinc transporterzinc starvationzinc excessZur regulonSmtB regulonMicrobiologyQR1-502ENmSystems, Vol 5, Iss 2 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	zinc homeostasis zinc transporter zinc starvation zinc excess Zur regulon SmtB regulon Microbiology QR1-502
spellingShingle	zinc homeostasis zinc transporter zinc starvation zinc excess Zur regulon SmtB regulon Microbiology QR1-502 Elke Goethe Kristin Laarmann Janita Lührs Michael Jarek Jochen Meens Astrid Lewin Ralph Goethe Critical Role of Zur and SmtB in Zinc Homeostasis of <named-content content-type="genus-species">Mycobacterium smegmatis</named-content>
description	ABSTRACT Zinc homeostasis is crucial for bacterial cells, since imbalances affect viability. However, in mycobacteria, knowledge of zinc metabolism is incomplete. Mycobacterium smegmatis (MSMEG) is an environmental, nonpathogenic Mycobacterium that is widely used as a model organism to study mycobacterial metabolism and pathogenicity. How MSMEG maintains zinc homeostasis is largely unknown. SmtB and Zur are important regulators of bacterial zinc metabolism. In mycobacteria, these regulators are encoded by an operon, whereas in other bacterial species, SmtB and Zur are encoded on separate loci. Here, we show that the smtB-zur operon is consistently present within the genus Mycobacterium but otherwise found only in Nocardia, Saccharothrix, and Corynebacterium diphtheriae. By RNA deep sequencing, we determined the Zur and SmtB regulons of MSMEG and compared them with transcriptional responses after zinc starvation or excess. We found an exceptional genomic clustering of genes whose expression was strongly induced by zur deletion and zinc starvation. These genes encoded zinc importers such as ZnuABC and three additional putative zinc transporters, including the porin MspD, as well as alternative ribosomal proteins. In contrast, only a few genes were affected by deletion of smtB and zinc excess. The zinc exporter ZitA was most prominently regulated by SmtB. Moreover, transcriptional analyses in combination with promoter and chromatin immunoprecipitation assays revealed a special regulation of the smtB-zur operon itself: an apparently zinc-independent, constitutive expression of smtB-zur resulted from sensitive coregulation by both SmtB and Zur. Overall, our data revealed yet unknown peculiarities of mycobacterial zinc homeostasis. IMPORTANCE Zinc is crucial for many biological processes, as it is an essential cofactor of enzymes and a structural component of regulatory and DNA binding proteins. Hence, all living cells require zinc to maintain constant intracellular levels. However, in excess, zinc is toxic. Therefore, cellular zinc homeostasis needs to be tightly controlled. In bacteria, this is achieved by transcriptional regulators whose activity is mediated via zinc-dependent conformational changes promoting or preventing their binding to DNA. SmtB and Zur are important antagonistically acting bacterial regulators in mycobacteria. They sense changes in zinc concentrations in the femtomolar range and regulate transcription of genes for zinc acquisition, storage, and export. Here, we analyzed the role of SmtB and Zur in zinc homeostasis in Mycobacterium smegmatis. Our results revealed novel insights into the transcriptional processes of zinc homeostasis in mycobacteria and their regulation.
format	article
author	Elke Goethe Kristin Laarmann Janita Lührs Michael Jarek Jochen Meens Astrid Lewin Ralph Goethe
author_facet	Elke Goethe Kristin Laarmann Janita Lührs Michael Jarek Jochen Meens Astrid Lewin Ralph Goethe
author_sort	Elke Goethe
title	Critical Role of Zur and SmtB in Zinc Homeostasis of <named-content content-type="genus-species">Mycobacterium smegmatis</named-content>
title_short	Critical Role of Zur and SmtB in Zinc Homeostasis of <named-content content-type="genus-species">Mycobacterium smegmatis</named-content>
title_full	Critical Role of Zur and SmtB in Zinc Homeostasis of <named-content content-type="genus-species">Mycobacterium smegmatis</named-content>
title_fullStr	Critical Role of Zur and SmtB in Zinc Homeostasis of <named-content content-type="genus-species">Mycobacterium smegmatis</named-content>
title_full_unstemmed	Critical Role of Zur and SmtB in Zinc Homeostasis of <named-content content-type="genus-species">Mycobacterium smegmatis</named-content>
title_sort	critical role of zur and smtb in zinc homeostasis of <named-content content-type="genus-species">mycobacterium smegmatis</named-content>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/78642ba8ad9444bf9e83df48c176ae47
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Critical Role of Zur and SmtB in Zinc Homeostasis of <named-content content-type="genus-species">Mycobacterium smegmatis</named-content>

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