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Infection and Immunity, July 2002, p. 3371-3381, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3371-3381.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

ideR, an Essential Gene in Mycobacterium tuberculosis: Role of IdeR in Iron-Dependent Gene Expression, Iron Metabolism, and Oxidative Stress Response{dagger}

G. Marcela Rodriguez,1 Martin I. Voskuil,2 Benjamin Gold,1,3 Gary K. Schoolnik,2 and Issar Smith1*

TB Center, The Public Health Research Institute, Newark, New Jersey 07103,1 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305,2 Department of Microbiology, New York University Medical Center, New York, New York 100163

Received 16 November 2001/ Returned for modification 14 January 2002/ Accepted 25 March 2002

The mycobacterial IdeR protein is a metal-dependent regulator of the DtxR (diphtheria toxin repressor) family. In the presence of iron, it binds to a specific DNA sequence in the promoter regions of the genes that it regulates, thus controlling their transcription. In this study, we provide evidence that ideR is an essential gene in Mycobacterium tuberculosis. ideR cannot normally be disrupted in this mycobacterium in the absence of a second functional copy of the gene. However, a rare ideR mutant was obtained in which the lethal effects of ideR inactivation were alleviated by a second-site suppressor mutation and which exhibited restricted iron assimilation capacity. Studies of this strain and a derivative in which IdeR expression was restored allowed us to identify phenotypic effects resulting from ideR inactivation. Using DNA microarrays, the iron-dependent transcriptional profiles of the wild-type, ideR mutant, and ideR-complemented mutant strains were analyzed, and the genes regulated by iron and IdeR were identified. These genes encode a variety of proteins, including putative transporters, proteins involved in siderophore synthesis and iron storage, members of the PE/PPE family, a membrane protein involved in virulence, transcriptional regulators, and enzymes involved in lipid metabolism.

* Corresponding author. Mailing address: TB Center, The Public Health Research Institute, 225 Warren St., Newark, NJ 07103. Phone: (212) 578-0867. Fax: (212) 578-0804. E-mail: smitty{at}phri.org.

{dagger} Publication no. 78 from the TB Center, The Public Health Research Institute, Newark, NJ 07103.

Editor: S. H. E. Kaufmann

Infection and Immunity, July 2002, p. 3371-3381, Vol. 70, No. 7
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.7.3371-3381.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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