ArticleAntimicrobial agents and chemotherapy2008
Identification of a novel multidrug efflux pump of Mycobacterium tuberculosis.
Article in Antimicrobial agents and chemotherapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 153 citations in OpenAlex.
- Variation in multiple classes of simple sequence repeats can alter drug susceptibility inbioRxiv : the preprint server for biology · 2026Article
- Key Proteins and Enzymatic Mechanisms Underlying Drug Resistance in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Protein Architecture and Composition in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Whole Genome Sequencing and Metabolomic Profiling of Six Clinical Mycobacterium Tuberculosis Isolates Reveal Drug Resistance-Associated Features.Current microbiology · 2025Article
- Flurbiprofen restores rifampicin and isoniazid sensitivity in multidrug-resistant Mycobacterium tuberculosis putatively by inhibiting efflux pumps Rv0194 and Rv0933.Folia microbiologica · 2025Article
- Cryo-EM structures of a mycobacterial ABC transporter that mediates rifampicin resistance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- EmbB and EmbC regulate the sensitivity ofmLife · 2024Article
- Prediction of Mycobacterium tuberculosis cell wall permeability using machine learning methods.Molecular diversity · 2024Article
- Intricate link between siderophore secretion and drug efflux inAntimicrobial agents and chemotherapy · 2023Article
- Ribosome-targeting antibiotics and resistanceRSC medicinal chemistry · 2023Review
- Mycobacterium tuberculosis Requires the Outer Membrane Lipid Phthiocerol Dimycocerosate for Starvation-Induced Antibiotic Tolerance.mSystems · 2023Article
- Mutations inAntimicrobial agents and chemotherapy · 2022Article
- Are the Newer Carbapenems of Any Value against Tuberculosis.Antibiotics (Basel, Switzerland) · 2022Article
- Experimental Confirmation that an UncommonAntimicrobial agents and chemotherapy · 2022Article
- Critical discussion on drug efflux in Mycobacterium tuberculosis.FEMS microbiology reviews · 2022Review
- Role of Efflux Pump-Mediated Antibiotic Resistance in Quorum Sensing-Regulated Biofilm Formation byPathogens (Basel, Switzerland) · 2022Article
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- The ATP-Binding Cassette (ABC) Transport Systems inBiology · 2020Review
- Targeting redox heterogeneity to counteract drug tolerance in replicatingScience translational medicine · 2019Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
Abstract
The impermeability of the outer membrane in combination with drug efflux are major determinants of the natural drug resistance of mycobacteria. beta-Lactams are the most widely used antibiotics for treatment of bacterial infections. However, it is unknown how beta-lactams enter Mycobacterium tuberculosis and whether efflux pumps exist that can export these drugs out of the cell. To identify the molecular mechanisms of M. tuberculosis resistance to beta-lactams, a library of 7,500 transposon mutants was generated in the model organism Mycobacterium bovis BCG. Thirty-three unique insertion sites were determined that conferred medium or high-level (> or =2,000 microg/ml) resistance to ampicillin. Three mutants in sulfolipid synthesis or transport were highly resistant to ampicillin, indicating an indirect effect of the lipid composition on the outer membrane permeability of M. bovis BCG to ampicillin. Mutants with insertions in genes encoding surface molecules such as PPE proteins or lipoarabinomannan were also completely resistant to ampicillin, thus suggesting a lack of transport across the outer membrane. Insertion of the transposon in front of bcg0231 increased transcription of the gene and concomitantly the resistance of M. bovis BCG to ampicillin, streptomycin, and chloramphenicol by 32- to 64-fold. Resistance to vancomycin and tetracycline was increased four- to eightfold. Bcg0231 and Rv0194 are almost identical ATP-binding cassette transporters. Expression of rv0194 significantly reduced accumulation of ethidium bromide and conferred multidrug resistance to Mycobacterium smegmatis. Both effects were abrogated in the presence of the efflux pump inhibitor reserpine. These results demonstrate that Rv0194 is a novel multidrug efflux pump of M. tuberculosis.
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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.