Recent Articles

Manganelli R, Voskuil MI, Schoolnik GK, Dubnau E, Gomez M, Smith I.
Role of the extracytoplasmic-function sigma Factor sigmaH in Mycobacteriumtuberculosis global gene expression.
Mol Microbiol 2002 Jul;45(2):365-74
PMID: 12123450

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 sigmaH. 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 sigmaH 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 sigmaH. 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 sigmaH control encode
transcriptional regulators such as sigB, sigE, and sigH itself.