ArticleScientific reports2019
Crystal structure of the multidrug resistance regulator RamR complexed with bile acids.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed.
- How resistance-nodulation-division (RND) efflux pumps contribute to virulence.PLoS pathogens · 2026Review
- CDCA-Derived NE3TA Conjugate for Liver-SelectiveACS omega · 2026Article
- Conserved Motifs in the Ligand-Binding Domain of TetR Family Regulators: Identification and Analysis.Computational and structural biotechnology journal · 2026Article
- Structure-guided discovery and validation of a potent RamR inhibitor targeting efflux-mediated multidrug resistance in Salmonella typhimurium.Folia microbiologica · 2025Article
- Investigating the Chemical-Biological Link inFood science & nutrition · 2025Article
- Phenotypic and genomic changes in entericmSphere · 2024Article
- RND Efflux Pump Induction: A Crucial Network Unveiling Adaptive Antibiotic Resistance Mechanisms of Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2024Review
- Hormonal steroids induce multidrug resistance and stress response genes in Neisseria gonorrhoeae by binding to MtrR.Nature communications · 2024Article
- Phenolic Compound, Antioxidant, Antibacterial, and In Silico Studies of Extracts from the Aerial Parts ofMolecules (Basel, Switzerland) · 2024Article
- Major primary bile salts repressFrontiers in microbiology · 2024Article
- The Mar, Sox, and Rob Systems.EcoSal Plus · 2023Review
- Article
- Drug resistance and physiological roles of RND multidrug efflux pumps inMicrobiology (Reading, England) · 2023Article
- Molecular mechanisms of antibiotic resistance revisited.Nature reviews. Microbiology · 2023Review
- Phytocompounds from Himalayan Medicinal Plants as Potential Drugs to Treat Multidrug-ResistantBiomedicines · 2021Article
- Transcriptional Regulation of the Multiple Resistance Mechanisms inPathogens (Basel, Switzerland) · 2021Review
- Chemogenetic Tags with Probe Exchange for Live-Cell Fluorescence Microscopy.ACS chemical biology · 2021Article
- Structural basis for selective inhibition of human serine hydroxymethyltransferase by secondary bile acid conjugate.iScience · 2021Article
- Function and Inhibitory Mechanisms of Multidrug Efflux Pumps.Frontiers in microbiology · 2021Review
- The Great ESKAPE: Exploring the Crossroads of Bile and Antibiotic Resistance in Bacterial Pathogens.Infection and immunity · 2020Review
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During infection, Salmonella senses and responds to harsh environments within the host. Persistence in a bile-rich environment is important for Salmonella to infect the small intestine or gallbladder and the multidrug efflux system AcrAB-TolC is required for bile resistance. The genes encoding this system are mainly regulated by the ramRA locus, which is composed of the divergently transcribed ramA and ramR genes. The acrAB and tolC genes are transcriptionally activated by RamA, whose encoding gene is itself transcriptionally repressed by RamR. RamR recognizes multiple drugs; however, the identity of the environmental signals to which it responds is unclear. Here, we describe the crystal structures of RamR in complexes with bile components, including cholic acid and chenodeoxycholic acid, determined at resolutions of 2.0 and 1.8 Å, respectively. Both cholic and chenodeoxycholic acids form four hydrogen bonds with Tyr59, Thr85, Ser137 and Asp152 of RamR, instead of π-π interactions with Phe155, a residue that is important for the recognition of multiple compounds including berberine, crystal violet, dequalinium, ethidium bromide and rhodamine 6 G. Binding of these compounds to RamR reduces its DNA-binding affinity, resulting in the increased transcription of ramA and acrAB-tolC. Our results reveal that Salmonella senses bile acid components through RamR and then upregulates the expression of RamA, which can lead to induction of acrAB-tolC expression with resulting tolerance to bile-rich environments.
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