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dc.contributor.authorGoethe, Elke
dc.contributor.authorLaarmann, Kristin
dc.contributor.authorLührs, Janita
dc.contributor.authorJarek, Michael
dc.contributor.authorMeens, Jochen
dc.contributor.authorLewin, Astrid
dc.contributor.authorGoethe, Ralph
dc.date.accessioned2022-06-16T12:23:32Z
dc.date.available2022-06-16T12:23:32Z
dc.date.issued2020-04-21
dc.date.submitted2019-12-13
dc.identifier.issn2379-5077
dc.identifier.pmid32317393
dc.identifier.doi10.1128/mSystems.00880-19
dc.identifier.urihttp://hdl.handle.net/10033/623230
dc.description.abstractZinc 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.en_US
dc.language.isoenen_US
dc.rightsAttribution 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectSmtB regulonen_US
dc.subjectZur regulonen_US
dc.subjectalternative ribosomal proteinsen_US
dc.subjectchromatin immunoprecipitationen_US
dc.subjectcoregulationen_US
dc.subjectexporten_US
dc.subjectimporten_US
dc.subjectmycobacteriaen_US
dc.subjecttranscriptomicsen_US
dc.subjectzinc excessen_US
dc.subjectzinc exporten_US
dc.subjectzinc homeostasisen_US
dc.subjectzinc importen_US
dc.subjectzinc regulationen_US
dc.subjectzinc starvationen_US
dc.subjectzinc transporteren_US
dc.subjectzitAen_US
dc.subjectznuABCen_US
dc.titleCritical Role of Zur and SmtB in Zinc Homeostasis of Mycobacterium smegmatis.en_US
dc.typeArticleen_US
dc.identifier.journalmSystemsen_US
dc.source.volume5
dc.source.issue2
refterms.dateFOA2022-06-16T12:23:32Z
dc.source.journaltitlemSystems
dc.source.countryUnited States


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Attribution 4.0 International
Except where otherwise noted, this item's license is described as Attribution 4.0 International