A highly conserved transcriptional repressor controls a large regulon involved in lipid degradation inMycobacterium smegmatisandMycobacterium tuberculosis

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Abstract
Summary: TheMycobacterium tuberculosisTetR‐type regulatorRv3574has been implicated in pathogenesis as it is inducedin vivo, and genome‐wide essentiality studies show it is required for infection. As the gene is highly conserved in the mycobacteria, we deleted theRv3574orthologue inMycobacterium 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 ofM. tuberculosisandM. smegmatisrespectively. Combining the results of the microarray studies with the motif analyses, we predict thatRv3574directly controls the expression of 83 genes inM. smegmatis, and 74 inM. tuberculosis. Many of these genes are known to be induced by growth on cholesterol in rhodococci, and palmitate inM. tuberculosis. We conclude that this regulator, designated elsewhere askstR, controls the expression of genes used for utilizing diverse lipids as energy sources, possibly imported through themce4system.

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