Role of the extracytoplasmic-function σ Factor σH in Mycobacterium tuberculosis global gene expression

Authors

  • Riccardo Manganelli,

    1. TB Center, The Public Health Research Institute at the International Center for Public Health, Newark, NJ 07103–3506, USA.
    2. Department of Histology, Microbiology and Medical Biotechnologies, University of Padua, 35121 Padua, Italy.
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  • Martin I. Voskuil,

    1. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
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  • Gary K. Schoolnik,

    1. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA.
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  • Eugenie Dubnau,

    1. TB Center, The Public Health Research Institute at the International Center for Public Health, Newark, NJ 07103–3506, USA.
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  • Manuel Gomez,

    1. TB Center, The Public Health Research Institute at the International Center for Public Health, Newark, NJ 07103–3506, USA.
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  • Issar Smith

    Corresponding author
    1. TB Center, The Public Health Research Institute at the International Center for Public Health, Newark, NJ 07103–3506, USA.
    • *For correspondence. E-mail smitty@phri.org; Tel. (+1) 973 972 9150; Fax (+1) 973 972 9150

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Summary

Like other bacterial species, Mycobacterium tuberculosis has multiple sigma (σ) factors encoded in its genome. In previously published work, we and others have shown that mutations in some of these transcriptional activators render M. tuberculosis sensitive to various environmental stresses and, in some cases, cause attenuated virulence phenotypes. In this paper, we characterize a M. tuberculosis mutant lacking the ECF σ factor σH. This mutant was more sensitive than the wild type to heat shock and to various oxidative stresses, but did not show de-creased ability to grow inside macrophages. Using quantitative reverse transcription-PCR and microarray technology, we have started to define the σH regulon and its involvement in the global regulation of the response to heat shock and the thiol-specific oxidizing agent diamide. We identified 48 genes whose expression increased after exposure of M. tuberculosis to diamide; out of these, 39 were not induced in the sigH mutant, showing their direct or indirect dependence on σH. Some of these genes encode proteins whose predicted function is related to thiol metabolism, such as thioredoxin, thioredoxin reductase and enzymes involved in cysteine and molybdopterine biosynthesis. Other genes under σH control encode transcriptional regulators such as sigB, sigE, and sigH itself.

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