Regulation of Aromatic Compounds and Environmental Stimuli Response by the MarR Family Regulator AesR in...

The MarR family regulators, widespread in bacteria and archaea, control diverse cellular processes, yet the regulatory mode and molecular signaling mechanism remain unclear in Corynebacterium glutamicum. Here, we functionally characterize AesR (aromatic compounds and environmental stimuli-sensing regulator), a MarR-type transcriptional regulator encoded by ncgl0019 in C. glutamicum. RNA sequencing (RNA-seq) analysis of an aesR-deleted strain (ΔaesR) revealed the down-regulation of genes involved in aromatic compounds degradation, stress response, antibiotic resistance and cell envelope biogenesis, correlating with heightened sensitivity of ΔaesR to adverse conditions. RNA-seq, quantitative reverse transcription-PCR (qRT-PCR) and promoter activity analysis uncovered that AesR represses its own operon (including the Zn-dependent protease with chaperone function gene ncgl0020) and the divergent cytochrome C biosynthesis operon ncgl0018-ncgl0017. AesR binds as a dimer to two side-by-side inverted repeats [5'-ACTATG-N₃-CATAGTCGACTA-N₇-TAGTTG-3'] in the ncgl0018-aesR intergenic region with different affinity, and Cu²⁺/Ni²⁺/Zn²⁺ disrupted binding. These metal ions, along with aromatic compounds, organic peroxides, and bactericidal antibiotics, induce both operons in vivo. Notably, penicillin elevates intracellular Cu²⁺/Ni²⁺/Zn²⁺ levels. Collectively, our findings identify AesR as a novel regulator that senses metal ions as direct signals, relieving autorepression and enabling bacterial defense against aromatic compounds and environmental stressors.