ArticleAntimicrobial agents and chemotherapy2015
The Mycobacterium tuberculosis outer membrane channel protein CpnT confers susceptibility to toxic molecules.
Article in Antimicrobial agents and chemotherapy, 2015. 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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27 citing papers in PubMed, 49 citations in OpenAlex.
- Protein Architecture and Composition in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Reimagining tuberculosis elimination in India: diagnostics, drug resistance, and digital health strategies.Frontiers in epidemiology · 2026Review
- Integrating Docking, Dynamics, and Assays to Predict Antimicrobial Peptide Interactions with Mycolic Acid Membranes inACS measurement science au · 2025Article
- Cell envelope diversity and evolution across the bacterial tree of life.Nature microbiology · 2024Review
- Impact of MSMEG5257 Deletion onMicroorganisms · 2024Article
- Recent Biochemical Advances in Antitubercular Drugs: Challenges and Future.Current topics in medicinal chemistry · 2024Review
- OvercomingACS omega · 2023Review
- Gated Calcium Ion Channel and Mutation Mechanisms in Multidrug-Resistant Tuberculosis.International journal of molecular sciences · 2023Review
- Understanding the Phage-Host Interaction Mechanism toward Improving the Efficacy of Current Antibiotics inBiomedicines · 2023Article
- HIV/Mtb Co-Infection: From the Amplification of Disease Pathogenesis to an "Emerging Syndemic".Microorganisms · 2023Review
- Liposomal Delivery of Saquinavir to Macrophages Overcomes Cathepsin Blockade byInternational journal of molecular sciences · 2023Article
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- Spatial localization of cathepsins: Implications in immune activation and resolution during infections.Frontiers in immunology · 2022Review
- Transporters Involved in the Biogenesis and Functionalization of the Mycobacterial Cell Envelope.Chemical reviews · 2021Review
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- Evolution of Drug-ResistantFrontiers in microbiology · 2021Review
- Non-Tuberculous Mycobacteria: Molecular and Physiological Bases of Virulence and Adaptation to Ecological Niches.Microorganisms · 2020Review
- High resolution CryoEM structure of the ring-shaped virulence factor EspB fromJournal of structural biology: X · 2020Article
- Unraveling the Structure of the Mycobacterial Envelope.Microbiology spectrum · 2019Review
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Authors and funding
4 authors at 2 institutions in 2 countries.
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Abstract
Mycobacterium tuberculosis, the causative agent of tuberculosis, is protected from toxic solutes by an effective outer membrane permeability barrier. Recently, we showed that the outer membrane channel protein CpnT is required for efficient nutrient uptake by M. tuberculosis and Mycobacterium bovis BCG. In this study, we found that the cpnT mutant of M. bovis BCG is more resistant than the wild type to a large number of drugs and antibiotics, including rifampin, ethambutol, clarithromycin, tetracycline, and ampicillin, by 8- to 32-fold. Furthermore, the cpnT mutant of M. bovis BCG was 100-fold more resistant to nitric oxide, a major bactericidal agent required to control M. tuberculosis infections in mice. Thus, CpnT constitutes the first outer membrane susceptibility factor in slow-growing mycobacteria. The dual functions of CpnT in uptake of nutrients and mediating susceptibility to toxic molecules are reflected in macrophage infection experiments: while loss of CpnT was detrimental for M. bovis BCG in macrophages that enable bacterial replication, presumably due to inadequate nutrient uptake, it conferred a survival advantage in macrophages that mount a strong bactericidal response. Importantly, the cpnT gene showed a significantly higher density of nonsynonymous mutations in drug-resistant clinical M. tuberculosis strains, indicating that CpnT is under selective pressure in human tuberculosis and/or during chemotherapy. Our results indicate that the CpnT channel constitutes an outer membrane gateway controlling the influx of nutrients and toxic molecules into slow-growing mycobacteria. This study revealed that reducing protein-mediated outer membrane permeability might constitute a new drug resistance mechanism in slow-growing mycobacteria.
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