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.
journal_name
Nat Communjournal_title
Nature communicationsauthors
Wang F,He Q,Yin J,Xu S,Hu W,Gu Ldoi
10.1038/s41467-018-05004-ysubject
Has Abstractpub_date
2018-07-02 00:00:00pages
2563issue
1issn
2041-1723pii
10.1038/s41467-018-05004-yjournal_volume
9pub_type
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