3.2.1. Ethoxzolamide

Using a pH-inducible fluorescence reporter system Johnson et al. phenotypically screened for inhibitors of the PhoPR regulon (Figure 1). This screening discovered the carbonic anhydrase inhibitor ethoxzolamide, which inhibits PhoPR while not reducing mycobacterial growth in vitro. Chromatin immunoprecipitation followed by deep sequencing (ChIP-seq) of compound-exposed *M. tuberculosis* cultivated in medium at pH 5.7 showed downregulation of several PhoPR regulated genes involved in lipid synthesis, carbon metabolism and virulence. In addition, the presence of ethoxzolamide did not modulate the expression levels of PhoP itself indicating that the substance acts as a direct inhibitor of the core PhoPR regulon [109].
