Regulation by Exile: How a Transcription Factor Regulates A Secretion System

Source: Raghavan et al (2008). Secreted transcription factor controls Mycobacterium tuberculosis virulence. Nature 454:717-721.

M. tuberculosis relies on a Type VII secretion system, termed ESX-1, to export the virulence factors targeting the host macrophages. In a transposon mutation genetic screen, the authors stumbled upon a mutant with elevated levels of IL-12 from macrophages (a common trait of ESX-1 mutants). They map the insertion to 13 nt upstream of Rv3849 which they later renames EspR. They made two other key observations:

1. EspR is a substrate of ESX-1, thus exported from the cell.
2. EspR is required for the transcription regulation of ESX-1.

The authors established a homology between EspR and SinR (a HTH transcription factor in B. subtilis). Subsequent microarray experiments showed that EspR regulates ESX-1 proteins. The conclusion is ESX-1 by exporting EspR creates a negative feedback loop for the control of its expression.