A highly conserved transcriptional repressor controls a large regulon involved in lipid degradation in Mycobacterium smegmatis and Mycobacterium tuberculosis.
The Mycobacterium tuberculosis TetR-type regulator Rv3574 has been implicated in pathogenesis as it is induced in vivo, and genome-wide essentiality studies show it is required for infection. As the gene is highly conserved in the mycobacteria, we deleted the Rv3574 orthologue in Mycobacterium smegmatis (MSMEG_6042) and used real-time quantitative polymerase chain reaction and microarray analyses to show that it represses the transcription both of itself and of a large number of genes involved in lipid metabolism. We identified a conserved motif within its own promoter (TnnAACnnGTTnnA) and showed that it binds as a dimer to 29 bp probes containing the motif. We found 16 and 31 other instances of the motif in intergenic regions of M. tuberculosis and M. smegmatis respectively. Combining the results of the microarray studies with the motif analyses, we predict that Rv3574 directly controls the expression of 83 genes in M. smegmatis, and 74 in M. tuberculosis. Many of these genes are known to be induced by growth on cholesterol in rhodococci, and palmitate in M. tuberculosis. We conclude that this regulator, designated elsewhere as kstR, controls the expression of genes used for utilizing diverse lipids as energy sources, possibly imported through the mce4 system.
Kendall
Sharon L
SL
Department of Pathology and Infectious Diseases, The Royal Veterinary College, Royal College Street, London NW1 0TU, UK.
Withers
Mike
M
Soffair
Catherine N
CN
Moreland
Nicole J
NJ
Gurcha
Sudagar
S
Sidders
Ben
B
Frita
Rosangela
R
Ten Bokum
Annemieke
A
Besra
Gurdyal S
GS
Lott
J Shaun
JS
Stoker
Neil G
NG
D020816:Amino Acid Motifs; D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D001483:Base Sequence; D017124:Conserved Sequence; D021901:DNA, Intergenic / Q000235:genetics; D019281:Dimerization; D015964:Gene Expression Regulation, Bacterial; D005798:Genes, Bacterial; D050356:Lipid Metabolism / Q000235:genetics*; D008969:Molecular Sequence Data; D020102:Mycobacterium smegmatis / Q000235:genetics* / Q000254:growth & development; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000254:growth & development; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D018085:Regulon / Q000235:genetics*; D012097:Repressor Proteins / Q000378:metabolism*; D017384:Sequence Deletion; D014158:Transcription, Genetic; D015854:Up-Regulation / Q000235:genetics
D001426:Bacterial Proteins; D021901:DNA, Intergenic; D012097:Repressor Proteins