Crystal structure of BrlR reveals a potential pyocyanin binding site

The transcriptional regulator BrlR from Pseudomonas aeruginosa is a member of the MerR family. Studies have shown BrlR can be activated by the secondary messenger 3′,5′-cyclic diguanylic acid (c-di-GMP) and contributes to P. aeruginosa biofilm tolerance. Previous structural analysis of BrlR-c-di-GMP complex has identified one hydrophobic pocket locating in its C-terminal GyrI-like domain. However, what kind of small molecule bound in this pocket remains unknown. Here, we report the apo structure of BrlR and identified the direct binding between GyrI-like domain of BrlR and Pseudomonas aeruginosa toxin pyocyanin. Furthermore, pyocyanin can enhance the binding between BrlR and DNA in vitro. These novel findings suggest BrlR functions as one shared receptor for c-di-GMP and pyocyanin. The structural analysis also provide an important basis for rational drug design combating the infection of P. aeruginosa.