ArticleThe Journal of biological chemistry2014
The DrrAB efflux system of Streptomyces peucetius is a multidrug transporter of broad substrate specificity.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 62 citations in OpenAlex.
- Nanoparticle-Based Approaches for Glioblastoma Treatment: Advances and Future Prospects.CNS & neurological disorders drug targets · 2026Review
- Brain Delivery Strategies for Biomacromolecular Drugs: Intranasal Administration.International journal of nanomedicine · 2025Review
- The Daunomycin: Biosynthesis, Actions, and the Search for New Solutions to Enhance Production.Microorganisms · 2024Review
- The involvement of multiple ABC transporters in daunorubicin efflux in Streptomyces coeruleorubidus.Microbial biotechnology · 2024Article
- Enhancement of doxorubicin production in Streptomyces peucetius by genetic engineering and process optimization.AMB Express · 2024Article
- Recent Advances in Understanding the Molecular Mechanisms of Multidrug Resistance and Novel Approaches of CRISPR/Cas9-Based Genome-Editing to Combat This Health Emergency.International journal of nanomedicine · 2024Review
- Damage mechanism and therapy progress of the blood-brain barrier after ischemic stroke.Cell & bioscience · 2023Review
- Involvement of the SCO3366 efflux pump from S. coelicolor in rifampicin resistance and its regulation by a TetR regulator.Applied microbiology and biotechnology · 2022Article
- Environmental antibiotics and resistance genes as emerging contaminants: Methods of detection and bioremediation.Current research in microbial sciences · 2021Review
- Identification of Novel Rotihibin Analogues inMicrobiology spectrum · 2021Article
- The Whole Is Bigger than the Sum of Its Parts: Drug Transport in the Context of Two Membranes with Active Efflux.Chemical reviews · 2021Article
- A Major Facilitator Superfamily (MFS) Efflux Pump, SCO4121, from Streptomyces coelicolor with Roles in Multidrug Resistance and Oxidative Stress Tolerance and Its Regulation by a MarR Regulator.Applied and environmental microbiology · 2021Article
- Cloning and Functional Characterization of PutativeJournal of microbiology and biotechnology · 2020Article
- A Putative Efflux Transporter of the ABC Family, YbhFSR, inFrontiers in microbiology · 2020Article
- Nanomaterial-based blood-brain-barrier (BBB) crossing strategies.Biomaterials · 2019Review
- Biochemical characterization of the mouse ABCF3 protein, a partner of the flavivirus-resistance protein OAS1B.The Journal of biological chemistry · 2019Article
- Conformational changes in a multidrug resistance ABC transporter DrrAB: Fluorescence-based approaches to study substrate binding.Archives of biochemistry and biophysics · 2018Article
- Antibiotic Resistance Mechanisms in Bacteria: Relationships Between Resistance Determinants of Antibiotic Producers, Environmental Bacteria, and Clinical Pathogens.Frontiers in microbiology · 2018Review
- Novel Antibiotic Resistance Determinants from Agricultural Soil Exposed to Antibiotics Widely Used in Human Medicine and Animal Farming.Applied and environmental microbiology · 2017Article
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3 authors at 1 institution in 1 country.
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Abstract
The soil bacterium Streptomyces peucetius produces two widely used anticancer antibiotics, doxorubicin and daunorubicin. Present within the biosynthesis gene cluster in S. peucetius is the drrAB operon, which codes for a dedicated ABC (ATP binding cassette)-type transporter for the export of these two closely related antibiotics. Because of its dedicated nature, the DrrAB system is believed to belong to the category of single-drug transporters. However, whether it also contains specificity for other known substrates of multidrug transporters has never been tested. In this study we demonstrate under both in vivo and in vitro conditions that the DrrAB system can transport not only doxorubicin but is also able to export two most commonly studied MDR substrates, Hoechst 33342 and ethidium bromide. Moreover, we demonstrate that many other substrates (including verapamil, vinblastine, and rifampicin) of the well studied multidrug transporters inhibit DrrAB-mediated Dox transport with high efficiency, indicating that they are also substrates of the DrrAB pump. Kinetic studies show that inhibition of doxorubicin transport by Hoechst 33342 and rifampicin occurs by a competitive mechanism, whereas verapamil inhibits transport by a non-competitive mechanism, thus suggesting the possibility of more than one drug binding site in the DrrAB system. This is the first in-depth study of a drug resistance system from a producer organism, and it shows that a dedicated efflux system like DrrAB contains specificity for multiple drugs. The significance of these findings in evolution of poly-specificity in drug resistance systems is discussed.
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