Leaving on the lights:: host-specific derepression of Mycobacterium tuberculosis gene expression by anti-sigma factor gene mutations

Regulation of transcription by alternative sigma factors is a strategy widely used by bacteria to adapt to changes in environmental conditions. For several pathogenic bacteria, alternative sigma factor-regulated gene expression is critical for virulence. The activity of many alternative sigma factors is in turn controlled by regulatory proteins that transduce and integrate environmental signals. In this issue of Molecular Microbiology, Said-Salim et al. demonstrate high-level expression of genes encoding major protein antigens in the bovine subspecies of Mycobacterium tuberculosis, in contrast to low-level expression in the human subspecies. Having previously suggested that SigK regulates the expression of these genes, the authors found that the high-expressers have point mutations in Rv0444c, a gene adjacent to sigK, and provided evidence that this gene encodes an anti-sigma factor whose function is abrogated by these mutations. These findings not only demonstrate an adaptive mechanism of potential importance in tuberculosis immunity and pathogenesis, but also raise interesting questions regarding the origin of these mutations and their effects on anti-sigma factor function.