Cholesterol utilization in mycobacteria is controlled by two TetR-type transcriptional regulators: kstR and kstR2
Kendall, Sharon L. and Burgess, Philippa and Balhana, Ricardo and Withers, Mike and ten Bokum, Annemieke and Lott, J. Shaun and Gao, Chen and Uhia-Castro, Iria and Stoker, Neil G.,, 156, 1362-1371 (2010),
doi = https://doi.org/10.1099/mic.0.034538-0,
publicationName = Microbiology Society,
issn = 1350-0872,
abstract= Mycobacterium tuberculosis is able to use a variety of carbon sources in vivo and current knowledge suggests that cholesterol is used as a carbon source during infection. The catabolized cholesterol is used both as an energy source (ATP generation) and as a source of precursor molecules for the synthesis of complex methyl-branched fatty acids. In previous studies, we described a TetR-type transcriptional repressor, kstR, that controls the expression of a number of genes involved in cholesterol catabolism. In this study, we describe a second TetR-type repressor, which we call kstR2. We knocked this gene out in Mycobacterium smegmatis and used microarrays and quantitative RT-PCR to examine the effects on gene expression. We identified a palindromic regulatory motif for KstR2, showed that this motif is present in three promoter regions in mycobacteria and rhodococcus, and demonstrated binding of purified KstR2 to the motif. Using a combination of motif location analysis, gene expression analysis and the examination of gene conservation, we suggest that kstR2 controls the expression of a 15 gene regulon. Like kstR, kstR2 and the kstR2 regulon are highly conserved among the actinomycetes and studies in rhodococcus suggest a role for these genes in cholesterol catabolism. The functional significance of the regulon and implications for the control of cholesterol utilization are discussed.,
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