The ARC2 response in Streptomcyes coelicolor requires the global regulatory genes afsR and afsS

ARC2 is a synthetic compound, related in structure and mechanism to the antibiotic triclosan, that activates the production of many specialized metabolites in the genus of bacteria. In this work, we demonstrate that the addition of ARC2 to cultures results in considerable alterations in overall gene expression including most notably the specialized metabolic genes. Using actinorhodin production as a model system, we show that the effect of ARC2 depends on the pleiotropic regulators and but not . We find that the constitutive expression of can bypass the need for but not the reverse, while the constitutive expression of had no effect on actinorhodin production. These data are consistent with a model in which ARC2 activates a cell stress response that depends on AfsR activating the expression of the gene such that AfsS then triggers the production of actinorhodin.