KstR is a transcription factor known to be involved in lipid and cholesterol degradation [36, 37] . It has been recently shown that Mtb uses cholesterol as a carbon source within the host [32] . Strikingly, KstR exhibits an evolutionary history that parallels the expansion of lipid metabolism genes in the Mycobacteria, and displays a singular conservation in its regulatory binding sites. KstR appears to have evolved at the last common ancestor of the Mycobacteria and Rhodococcus. In all Figure S1 ). Remarkably, these paralogs of KstR are all absent in the pathogenic Mycobacteria. Thus, coincident with the expansion in lipid metabolism genes described above, the KstR gene appears to have emerged through gene duplication within the existing gene family of tetR-like transcriptional regulators at the last common ancestor of Mycobacteria and Rhodococcus.