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BrlR from Pseudomonas aeruginosa is a receptor for both cyclic di-GMP and pyocyanin.

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.

SUBMITTER: Wang F

PROVIDER: S-EPMC6028453 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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BrlR from Pseudomonas aeruginosa is a receptor for both cyclic di-GMP and pyocyanin.

Wang Feng F He Qing Q Yin Jia J Xu Sujuan S Hu Wei W Gu Lichuan L

Nature communications 20180702 1

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 ...[more]

PMID: 29967320

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Dataset Information

BrlR from Pseudomonas aeruginosa is a receptor for both cyclic di-GMP and pyocyanin.

Publications

BrlR from Pseudomonas aeruginosa is a receptor for both cyclic di-GMP and pyocyanin.

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