ArticleAntimicrobial agents and chemotherapy2009
Role of the Mycobacterium tuberculosis P55 efflux pump in intrinsic drug resistance, oxidative stress responses, and growth.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 131 citations in OpenAlex.
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- Verapamil Suppresses the Development of Resistance Against Anti-Tuberculosis Drugs in Mycobacteria.International journal of molecular sciences · 2025Article
- Innovative Strategies for Combating Multidrug-Resistant Tuberculosis: Advances in Drug Delivery Systems and Treatment.Microorganisms · 2025Review
- The geneAntimicrobial agents and chemotherapy · 2025Article
- Structure and function ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Tuberculosis-diabetes comorbidities: Mechanistic insights for clinical considerations and treatment challenges.World journal of diabetes · 2024Review
- The efflux pumps Rv1877 and Rv0191 play differential roles in the protection ofFrontiers in microbiology · 2024Article
- Phenotypic drug susceptibility characterization and clinical outcomes of tuberculosis strains with A-probe mutation by GeneXpert MTB/RIF.BMC infectious diseases · 2023Article
- Structural basis for triacylglyceride extraction from mycobacterial inner membrane by MFS transporter Rv1410.Nature communications · 2023Article
- Mycobacterium tuberculosis Gene Expression Associated With Fluoroquinolone Resistance and Efflux Pump Inhibition.The Journal of infectious diseases · 2023Article
- Colloidal silver against macrophage infections and biofilms of atypical mycobacteria.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2023Article
- Antibiotic Resistance toAntibiotics (Basel, Switzerland) · 2022Review
- Alterations in molecular response of Mycobacterium tuberculosis against anti-tuberculosis drugs.Molecular biology reports · 2022Review
- Involvement of the SCO3366 efflux pump from S. coelicolor in rifampicin resistance and its regulation by a TetR regulator.Applied microbiology and biotechnology · 2022Article
- Critical discussion on drug efflux in Mycobacterium tuberculosis.FEMS microbiology reviews · 2022Review
- The Mycobacterial Efflux Pump EfpA Can Induce High Drug Tolerance to Many Antituberculosis Drugs, Including Moxifloxacin, in Mycobacterium smegmatis.Antimicrobial agents and chemotherapy · 2021Article
- Selective Targeting of Human and Animal Pathogens of theInternational journal of molecular sciences · 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
- Are Bacterial Persisters Dormant Cells Only?Frontiers in microbiology · 2021Review
- Efflux Pumps Contribute to Intrinsic Clarithromycin Resistance in Clinical,Infection and drug resistance · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bacterial efflux pumps have traditionally been studied as low-level drug resistance determinants. Recent insights have suggested that efflux systems are often involved with fundamental cellular physiological processes, suggesting that drug extrusion may be a secondary function. In Mycobacterium tuberculosis, little is known about the physiological or drug resistance roles of efflux pumps. Using Mycobacterium bovis BCG as a model system, we showed that deletion of the Rv1410c gene encoding the P55 efflux pump made the strain more susceptible to a range of toxic compounds, including rifampin (rifampicin) and clofazimine, which are first- and second-line antituberculosis drugs. The efflux pump inhibitors carbonyl cyanide m-chlorophenylhydrazone (CCCP) and valinomycin inhibited the P55-determined drug resistance, suggesting the active export of the compounds by use of the transmembrane proton and electrochemical gradients as sources of energy. In addition, the P55 efflux pump mutant was more susceptible to redox compounds and displayed increased intracellular redox potential, suggesting an essential role of the efflux pump in detoxification processes coupled to oxidative balance within the cell. Finally, cells that lacked the p55 gene displayed smaller colony sizes and had a growth defect in liquid culture. This, together with an increased susceptibility to the cell wall-targeting compounds bacitracin and vancomycin, suggested that P55 is needed for proper cell wall assembly and normal growth in vitro. Thus, P55 plays a fundamental role in oxidative stress responses and in vitro cell growth, in addition to contributing to intrinsic antibiotic resistance. Inhibitors of the P55 efflux pump could help to improve current treatments for tuberculosis.
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