The Mycobacterium tuberculosis Extracytoplasmic-Function Sigma Factor SigL Regulates Polyketide Synthases and Secreted or Membrane Proteins and Is Required for Virulence
0301 basic medicine
Bodily Secretions
Mice, Inbred BALB C
Base Sequence
Transcription, Genetic
Virulence
Molecular Sequence Data
Membrane Proteins
Sigma Factor
Gene Expression Regulation, Bacterial
Mycobacterium tuberculosis
3. Good health
Mice
03 medical and health sciences
Phenotype
Mutation
Animals
Macrolides
Promoter Regions, Genetic
Tuberculosis, Pulmonary
DOI:
10.1128/jb.187.20.7062-7071.2005
Publication Date:
2005-09-30T16:23:42Z
AUTHORS (4)
ABSTRACT
ABSTRACT
Mycobacterium tuberculosis sigL
encodes an extracytoplasmic function (ECF) sigma factor and is adjacent to a gene for a membrane protein (Rv0736) that contains a conserved HXXXCXXC sequence. This motif is found in anti-sigma factors that regulate several ECF sigma factors, including those that control oxidative stress responses. In this work, SigL and Rv0736 were found to be cotranscribed, and the intracellular domain of Rv0736 was shown to interact specifically with SigL, suggesting that Rv0736 may encode an anti-sigma factor of SigL. An
M. tuberculosis sigL
mutant was not more susceptible than the parental strain to several oxidative and nitrosative stresses, and
sigL
expression was not increased in response to these stresses. In vivo,
sigL
is expressed from a weak SigL-independent promoter and also from a second SigL-dependent promoter. To identify SigL-regulated genes,
sigL
was overexpressed and microarray analysis of global transcription was performed. Four small operons,
sigL
(Rv0735)-Rv0736,
mpt53
(Rv2878c)-Rv2877c,
pks10
(Rv1660)-
pks7
(Rv1661), and Rv1139c-Rv1138c, were among the most highly upregulated genes in the
sigL
-overexpressing strain. SigL-dependent transcription start sites of these operons were mapped, and the consensus promoter sequences TGAACC in the −35 region and CGTgtc in the −10 region were identified. In vitro, purified SigL specifically initiated transcription from the promoters of
sigL, mpt53
, and
pks10
. Additional genes, including four PE_PGRS genes, appear to be regulated indirectly by SigL. In an in vivo murine infection model, the
sigL
mutant strain showed marked attenuation, indicating that the
sigL
regulon is important in
M. tuberculosis
pathogenesis.
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