Role of the extracytoplasmic-function sigma factor sigma(H) in Mycobacterium tuberculosis global gene expression

• Published in: Molecular microbiology Vol. 45; no. 2; pp. 365 - 374
• Main Authors: Manganelli, Riccardo, Voskuil, Martin I, Schoolnik, Gary K, Dubnau, Eugenie, Gomez, Manuel, Smith, Issar
• Format: Journal Article
• Language: English
• Published: England 01.07.2002
• Subjects: Animals; Bacterial Proteins - genetics; Bacterial Proteins - physiology; Base Sequence; Cell Line - microbiology; Consensus Sequence; Diamide - pharmacology; Gene Expression Profiling; Gene Expression Regulation, Bacterial; Genes, Bacterial; Hot Temperature; Humans; Macrophages - microbiology; Mice; Molecular Sequence Data; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - pathogenicity; Oxidative Stress; Sequence Alignment; Sequence Homology, Nucleic Acid; Sigma Factor - genetics; Sigma Factor - physiology; Sulfhydryl Reagents - pharmacology; Transcription, Genetic; Virulence
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1046/j.1365-2958.2002.03005.x

Like other bacterial species, Mycobacterium tuberculosis has multiple sigma (sigma) 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 sigma factor sigma(H). This mutant was more sensitive than the wild type to heat shock and to various oxidative stresses, but did not show decreased ability to grow inside macrophages. Using quantitative reverse transcription-PCR and microarray technology, we have started to define the sigma(H) 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 sigma(H). 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 sigma(H) control encode transcriptional regulators such as sigB, sigE, and sigH itself.