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J. Bacteriol. doi:10.1128/JB.01190-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Global analysis of Mycobacterium tuberculosis Zur (FurB) regulon

Anna Macig, Elisa Dainese, G. Marcela Rodriguez, Anna Milano, Roberta Provvedi, Maria R. Pasca, Issar Smith, Giorgio Palù, Giovanna Riccardi, and Riccardo Manganelli^*

Department of Genetics and Microbiology, University of Pavia, Italy; Department of Histology, Microbiology and Medical Biotechnology, University of Padova, Italy; TB Center, The Public Health Research Institute, Newark, NJ, USA; Department of Biology, University of Padova, Italy

^* To whom correspondence should be addressed. Email: riccardo.manganelli{at}unipd.it.

	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 cationhomeostasis. The Mycobacterium tuberculosis genome encodes two Fur-like proteins, FurA and a protein formerly annotated as FurB. Since in this paper we show that it represents a Zinc Uptake Regulator, we will 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 for zinc homeostasis. In this paper we generated a zur mutant in M. tuberculosis, examined its phenotype and characterized the Zur regulon by using 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 8 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 the Early Secretory Antigen Target (ESAT)-6 cluster 3 and three additional proteins belonging to the ESAT-6/Culture Filtrate Protein (CFP)-10 family known to contain immunodominant epitopes in the T-cell response to M. tuberculosis infection.

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