FIGURE 1.

MarA, RamA and SoxS regulate fitness in response to environmental stress. Intracellular accumulation of a stressor is sensed by MarR, RamR, and/or SoxR, depending on the substrate. Subsequently, substrate binding to MarR, RamR, and SoxR prevents the repression of marA, ramA, and soxS expression, respectively. MarA, RamA, and SoxS activate transcription of a wide range of genes, which results in increased drug resistance. However, another set of genes are repressed in response, for example genes involved in biofilm formation and virulence. When intracellular concentrations of the inducer fall to basal levels, MarR, RamR, and SoxR are no longer inhibited and can bind to the promoter sequences of marA, ramA, and soxS, respectively, preventing their transcription. Pre-produced MarA, RamA, and SoxS are degraded by the Lon protease, and drug resistance, biofilm formation and virulence gene expression return to baseline levels.