Fig. 7.

Model for the regulation of Rv0081-Rv0088 in M. tuberculosis in response to growth under different environmental conditions. The Rv0081-Rv0088 locus is transcribed by two promoters upstream of Rv0081; P1 is activated by DosR but repressed by Rv0081 and MprA, and P2 is activated by MprA. During growth under physiological conditions (i.e., no environmental stimuli) (A), expression from P1 and P2 is low due to the general lack of DosR-P and MprA-P within the bacterium. Upon conditions that activate the DosRS-DosT/DevRS-Rv2027c TCSS, levels of DosR-P/DevR-P increase, leading to increased expression of Rv0081-Rv0088 from P1 (B). Similarly, growth of M. tuberculosis under conditions that activate the MprAB TCSS lead to increased levels of MprA-P and increased expression of Rv0081-Rv0088 from P2 (C). Over time, high levels of Rv0081 accumulate. In the absence of as-yet-undefined stimuli, Rv0081 binds its recognition sequence in the Rv0081 upstream region, physically blocking access by both DosR-P or MprA-P and repressing transcription from P1. However, in response to specific stimuli (i.e., high concentrations of metal, possibly), Rv0081 dissociates from the DNA, leading to derepression of Rv0081-Rv0088 expression from P1 or P2. For all panels, thick arrows indicate genes while thin arrows indicate sites of transcription. Wavy lines below genes indicate transcripts initiating from the designated promoter elements. DosR-P, green; MprA-P, orange; Rv0081 unmodified, red; Rv0081 modified, blue.