ArticleJournal of bacteriology2013
The MerR-like regulator BrlR confers biofilm tolerance by activating multidrug efflux pumps in Pseudomonas aeruginosa biofilms.
Article in Journal of bacteriology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Antimicrobial Tolerance in Biofilms.Microbiology spectrum · 2015Pooled it
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- Activation of theInfection and immunity · 2025Article
- FleQ finetunes the expression of a subset of BrlR-activated genes to enable antibiotic tolerance byJournal of bacteriology · 2025Article
- Choline metabolism modulates cyclic-di-GMP signaling and virulence of Pseudomonas aeruginosa in a macrophage infection model.BMC infectious diseases · 2024Article
- Distinct transcriptome and traits of freshly dispersedmSphere · 2024Article
- Regulation of Safracin Biosynthesis and Transport inMarine drugs · 2024Article
- Quorum Quenching Approaches against Bacterial-Biofilm-Induced Antibiotic Resistance.Antibiotics (Basel, Switzerland) · 2024Review
- Biofilm-producing and specific antibiotic resistance genes inIJID regions · 2024Article
- Antibiotic influx and efflux in Pseudomonas aeruginosa: Regulation and therapeutic implications.Microbial biotechnology · 2024Review
- Antibiofilm activity of marine microbial natural products: potential peptide- and polyketide-derived molecules from marine microbes toward targeting biofilm-forming pathogens.Journal of natural medicines · 2024Review
- Mechanisms of antibiotic resistance inBiofilm · 2023Article
- Light-Based Anti-Biofilm and Antibacterial Strategies.Pharmaceutics · 2023Review
- Drug resistance and physiological roles of RND multidrug efflux pumps inMicrobiology (Reading, England) · 2023Article
- MoaB1 Homologs Contribute to Biofilm Formation and Motility by Pseudomonas aeruginosa and Escherichia coli.Journal of bacteriology · 2023Article
- New understanding of multidrug efflux and permeation in antibiotic resistance, persistence, and heteroresistance.Annals of the New York Academy of Sciences · 2023Review
22 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
A defining characteristic of biofilms is antibiotic tolerance that can be up to 1,000-fold greater than that of planktonic cells. In Pseudomonas aeruginosa, biofilm tolerance to antimicrobial agents requires the biofilm-specific MerR-type transcriptional regulator BrlR. However, the mechanism by which BrlR mediates biofilm tolerance has not been elucidated. Genome-wide transcriptional profiling indicated that brlR was required for maximal expression of genes associated with antibiotic resistance, in particular those encoding the multidrug efflux pumps MexAB-OprM and MexEF-OprN. Chromatin immunoprecipitation (ChIP) analysis revealed a direct regulation of these genes by BrlR, with DNA binding assays confirming BrlR binding to the promoter regions of the mexAB-oprM and mexEF-oprN operons. Quantitative reverse transcriptase PCR (qRT-PCR) analysis further indicated BrlR to be an activator of mexAB-oprM and mexEF-oprN gene expression. Moreover, immunoblot analysis confirmed increased MexA abundance in cells overexpressing brlR. Inactivation of both efflux pumps rendered biofilms significantly more susceptible to five different classes of antibiotics by affecting MIC but not the recalcitrance of biofilms to killing by bactericidal agents. Overexpression of either efflux pump in a ΔbrlR strain partly restored tolerance of ΔbrlR biofilms to antibiotics. Expression of brlR in mutant biofilms lacking both efflux pumps partly restored antimicrobial tolerance of biofilms to wild-type levels. Our results indicate that BrlR acts as an activator of multidrug efflux pumps to confer tolerance to P. aeruginosa biofilms and to resist the action of antimicrobial agents.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.