BrlR From Pseudomonas Aeruginosa Is a Receptor for Both Cyclic di-GMP and Pyocyanin

Feng Wang, Qing He, Jia Yin, Sujuan Xu, Wei Hu, Lichuan Gu

Nat Commun. 2018 Jul 2;9(1):2563.

PMID: 29967320

Abstract:

The virulence factor pyocyanin and the intracellular second messenger cyclic diguanylate monophosphate (c-di-GMP) play key roles in regulating biofilm formation and multi-drug efflux pump expression in Pseudomonas aeruginosa. However, the crosstalk between these two signaling pathways remains unclear. Here we show that BrlR (PA4878), previously identified as a c-di-GMP responsive transcriptional regulator, acts also as a receptor for pyocyanin. Crystal structures of free BrlR and c-di-GMP-bound BrlR reveal that the DNA-binding domain of BrlR contains two separate c-di-GMP binding sites, both of which are involved in promoting brlR expression. In addition, we identify a pyocyanin-binding site on the C-terminal multidrug-binding domain based on the structure of the BrlR-C domain in complex with a pyocyanin analog. Biochemical analysis indicates that pyocyanin enhances BrlR-DNA binding and brlR expression in a concentration-dependent manner.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP85665-A	Pyocyanin		85-66-5	Price