ArticleProtein science : a publication of the Protein Society2010
Critical biophysical properties in the Pseudomonas aeruginosa efflux gene regulator MexR are targeted by mutations conferring multidrug resistance.
Article in Protein science : a publication of the Protein Society, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Artificial intelligence in protein-based detection and inhibition of AMR pathways.Journal of computer-aided molecular design · 2025Review
- Next-generation proteomics for quantitative Jumbophage-bacteria interaction mapping.Nature communications · 2023Article
- Small-angle x-ray and neutron scattering of MexR and its complex with DNA supports a conformational selection binding model.Biophysical journal · 2023Article
- Whole-Genome Sequencing Reveals Diversity of Carbapenem-ResistantAntimicrobial agents and chemotherapy · 2022Article
- Role of RND Efflux Pumps in Drug Resistance of Cystic Fibrosis Pathogens.Antibiotics (Basel, Switzerland) · 2021Review
- A MexR Mutation Which Confers Aztreonam Resistance toFrontiers in microbiology · 2021Article
- The Building Blocks of Antimicrobial Resistance inFrontiers in cellular and infection microbiology · 2021Review
- Rapid and Point-of-Care Testing in Respiratory Tract Infections: An Antibiotic Guardian?ACS pharmacology & translational science · 2020Review
- Tuning site-specific dynamics to drive allosteric activation in a pneumococcal zinc uptake regulator.eLife · 2018Article
- Functional Mechanism of the Efflux Pumps Transcription Regulators FromFrontiers in molecular biosciences · 2018Review
- Regulation of Metabolic Pathways by MarR Family Transcription Factors.Computational and structural biotechnology journal · 2017Review
- Histidine switch controlling pH-dependent protein folding and DNA binding in a transcription factor at the core of synthetic network devices.Molecular bioSystems · 2016Article
- The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria.Clinical microbiology reviews · 2015Review
- Pseudomonas aeruginosa Genome Evolution in Patients and under the Hospital Environment.Pathogens (Basel, Switzerland) · 2014Article
- Efflux pump regulatory genes mutations in multidrug resistance Pseudomonas aeruginosa isolated from wound infections in Isfahan hospitals.Advanced biomedical research · 2014Article
- Article
- Study of PcaV from Streptomyces coelicolor yields new insights into ligand-responsive MarR family transcription factors.Nucleic acids research · 2013Article
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10 authors.
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Abstract
The self-assembling MexA-MexB-OprM efflux pump system, encoded by the mexO operon, contributes to facile resistance of Pseudomonas aeruginosa by actively extruding multiple antimicrobials. MexR negatively regulates the mexO operon, comprising two adjacent MexR binding sites, and is as such highly targeted by mutations that confer multidrug resistance (MDR). To understand how MDR mutations impair MexR function, we studied MexR-wt as well as a selected set of MDR single mutants distant from the proposed DNA-binding helix. Although DNA affinity and MexA-MexB-OprM repression were both drastically impaired in the selected MexR-MDR mutants, MexR-wt bound its two binding sites in the mexO with high affinity as a dimer. In the MexR-MDR mutants, secondary structure content and oligomerization properties were very similar to MexR-wt despite their lack of DNA binding. Despite this, the MexR-MDR mutants showed highly varying stabilities compared with MexR-wt, suggesting disturbed critical interdomain contacts, because mutations in the DNA-binding domains affected the stability of the dimer region and vice versa. Furthermore, significant ANS binding to MexR-wt in both free and DNA-bound states, together with increased ANS binding in all studied mutants, suggest that a hydrophobic cavity in the dimer region already shown to be involved in regulatory binding is enlarged by MDR mutations. Taken together, we propose that the biophysical MexR properties that are targeted by MDR mutations-stability, domain interactions, and internal hydrophobic surfaces-are also critical for the regulation of MexR DNA binding.
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