BrlR (biofilm resistance locus regulator, PA4878) is a MerR-like transcriptional regulator of Pseudomonas aeruginosa with an N-terminal MerR helix-turn-helix DNA-binding domain and a C-terminal GyrI-like (Cass2) effector domain. It is expressed mainly in biofilms and is responsive to the second messenger c-di-GMP, which BrlR binds directly (one c-di-GMP per BrlR dimer) and which enhances its dimerisation and promoter binding; pyocyanin also enhances BrlR activity. BrlR binds its own promoter and activates the mexAB-oprM and mexEF-oprN multidrug efflux operons and several ABC transporters, which underlies the high-level antibiotic tolerance of P. aeruginosa biofilms. Unusually for the family it also represses the oprH-phoPQ operon, binding its promoter directly, and so lowers PhoPQ-driven colistin resistance.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000976 transcription cis-regulatory region binding | IMP PMID:24612375 BrlR from Pseudomonas aeruginosa is a c-di-GMP-responsive tr... | ACCEPT | Summary: CollecTF row. BrlR binds its own promoter (in vivo and in vitro DNA-binding assays) and the oprH promoter. Reason: Directly supported promoter binding; core to the TF function. Supporting Evidence: PMID:24612375 BrlR binds to its own promoter, likely via a MerR-like palindromic sequence |
| GO:0001216 DNA-binding transcription activator activity | IMP PMID:24612375 BrlR from Pseudomonas aeruginosa is a c-di-GMP-responsive tr... | ACCEPT | Summary: CollecTF row. BrlR activates efflux-pump operons by binding their promoters (UniProt, curated from several papers) and its own promoter. Reason: Core molecular function. Supporting Evidence: file:PSEAE/brlR/brlR-uniprot.txt Activates expression of operons encoding the multidrug efflux pumps MexAB-OprM and MexEF-OprN and several ABC transport systems, acting by direct binding to their respective promoters |
| GO:0003677 DNA binding | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the MerR HTH domain. Reason: Entailed by the accepted GO:0000976 transcription cis-regulatory region binding, which is_a DNA binding. |
| GO:0003700 DNA-binding transcription factor activity | IBA GO_REF:0000033 | TOO GENERAL | Summary: IBA from the PTN001575588 MerR-family IBD, which this gene helped seed. Sound at the node, but this review accepts the more specific activator activity. Reason: True; entailed by the accepted GO:0001216 activator activity row. |
| GO:0003700 DNA-binding transcription factor activity | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the MerR family signature. Reason: Entailed by the accepted GO:0001216 DNA-binding transcription activator activity, which is_a this term. |
| GO:0006355 regulation of DNA-templated transcription | IBA GO_REF:0000033 | TOO GENERAL | Summary: IBA from the PTN001575588 IBD, seeded by this gene's own PseudoCAP rows (expected self-appearance) and eight other MerR regulators, including the well-characterised E. coli CueR and ZntR. Sound at the node. Reason: True, but entailed by the accepted GO:0045893 and GO:0045892 rows on this gene. |
| GO:0006355 regulation of DNA-templated transcription | IEA GO_REF:0000002 | TOO GENERAL | Summary: InterPro2GO from the MerR HTH domain. Reason: Entailed by the accepted positive and negative regulation of transcription rows (both is_a GO:0006355). |
| GO:0032993 protein-DNA complex | IMP PMID:24612375 BrlR from Pseudomonas aeruginosa is a c-di-GMP-responsive tr... | KEEP AS NON CORE | Summary: CollecTF standard row recording the BrlR-promoter complex. Reason: True (BrlR-DNA complexes were detected) but adds little beyond the cis-regulatory binding row. |
| GO:0045892 negative regulation of DNA-templated transcription | IDA PMID:23935054 The MerR-like regulator BrlR impairs Pseudomonas aeruginosa ... | ACCEPT | Summary: PseudoCAP row and a seed of the PTN001575588 IBD. EMSA shows BrlR binding the oprH-phoPQ promoter and expression data show repression; direct evidence for the gene's own activity. Reason: Sound seed; BrlR is a dual-function regulator and repression of phoPQ is direct. Supporting Evidence: PMID:23935054 Taken together with the gene expression results, our findings indicate that BrlR is involved in transcriptional regulation of the oprH-phoPQ operon, acting as a repressor. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:22730129 The MerR-like transcriptional regulator BrlR contributes to ... | ACCEPT | Summary: PseudoCAP row and a seed of the PTN001575588 IBD. The cited abstract reports genetics and drug tolerance, not the direct assay behind an IDA, but the full text was not available. The claim itself is well supported by later direct promoter-binding and activation work. Reason: Claim is correct for BrlR; deferring to the curator on the evidence from a paper whose full text was not read. Supporting Evidence: file:PSEAE/brlR/brlR-uniprot.txt Activates expression of operons encoding the multidrug efflux pumps MexAB-OprM and MexEF-OprN |
| GO:0035438 cyclic-di-GMP binding | IDA PMID:24612375 BrlR from Pseudomonas aeruginosa is a c-di-GMP-responsive tr... | NEW | Summary: BrlR binds c-di-GMP in vitro at one c-di-GMP per BrlR dimer, and c-di-GMP enhances its dimerisation and DNA binding. Not in GOA. Reason: Direct binding assay on the purified protein; the ligand regulates BrlR's transcription factor activity. Supporting Evidence: PMID:24612375 BrlR was found to bind c-di-GMP in vitro at a ratio of one c-di-GMP per two BrlR. |
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Download this section (compressed HTML)Q: Is the c-di-GMP binding site in the C-terminal effector domain or at the dimer interface, and does c-di-GMP change BrlR's choice between activating (mex operons) and repressing (oprH-phoPQ) promoters?
Experiment: Map the c-di-GMP binding residues of purified BrlR by mutagenesis and test the variants for promoter binding and in vivo activation of mexA and repression of oprH.
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