title: Global analysis of the Mycobacterium tuberculosis Zur (FurB) regulon.
abstract: The proteins belonging to the Fur family are global regulators of gene expression involved in the response to several environmental stresses and to the maintenance of divalent cation homeostasis. The Mycobacterium tuberculosis genome encodes two Fur-like proteins, FurA and a protein formerly annotated FurB. Since in this paper we show that it represents a zinc uptake regulator, we refer to it as Zur. The gene encoding Zur is found in an operon together with the gene encoding a second transcriptional regulator (Rv2358). In a previous work we demonstrated that Rv2358 is responsible for the zinc-dependent repression of the Rv2358-zur operon, favoring the hypothesis that these genes represent key regulators of zinc homeostasis. In this study we generated a zur mutant in M. tuberculosis, examined its phenotype, and characterized the Zur regulon by DNA microarray analysis. Thirty-two genes, presumably organized in 16 operons, were found to be upregulated in the zur mutant. Twenty-four of them belonged to eight putative transcriptional units preceded by a conserved 26-bp palindrome. Electrophoretic mobility shift experiments demonstrated that Zur binds to this palindrome in a zinc-dependent manner, suggesting its direct regulation of these genes. The proteins encoded by Zur-regulated genes include a group of ribosomal proteins, three putative metal transporters, the proteins belonging to early secretory antigen target 6 (ESAT-6) cluster 3, and three additional proteins belonging to the ESAT-6/culture filtrate protein 10 (CFP-10) family known to contain immunodominant epitopes in the T-cell response to M. tuberculosis infection.
authors.affiliation: Department of Genetics and Microbiology, University of Pavia, Pavia, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Maciag
authors.forename: Elisa
authors.initials: E
authors.lastname: Dainese
authors.forename: G Marcela
authors.initials: GM
authors.lastname: Rodriguez
authors.forename: Anna
authors.initials: A
authors.lastname: Milano
authors.forename: Roberta
authors.initials: R
authors.lastname: Provvedi
authors.forename: Maria R
authors.initials: MR
authors.lastname: Pasca
authors.forename: Issar
authors.initials: I
authors.lastname: Smith
authors.forename: Giorgio
authors.initials: G
authors.lastname: Palù
authors.forename: Giovanna
authors.initials: G
authors.lastname: Riccardi
authors.forename: Riccardo
authors.initials: R
authors.lastname: Manganelli
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding; D018085:Regulon; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014774:Virulence / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D003850:Deoxyribonuclease I