The DOI matches its Crossref record; 3 of the 3 references it cites were found in a registry or an index.
MmpL3 Is the Cellular Target of the Antitubercular Pyrrole Derivative BM212
Open accessAbstract
The 1,5-diarylpyrrole derivative BM212 was previously shown to be active against multidrug-resistant clinical isolates and Mycobacterium tuberculosis residing within macrophages as well as against Mycobacterium avium and other atypical mycobacteria. To determine its mechanism of action, we identified the cellular target. Spontaneous Mycobacterium smegmatis , Mycobacterium bovis BCG, and M. tuberculosis H37Rv mutants that were resistant to BM212 were isolated. By the screening of genomic libraries and by whole-genome sequencing, we found that all the characterized mutants showed mutations in the mmpL3 gene, allowing us to conclude that resistance to BM212 maps to the MmpL3 protein, a member of the MmpL ( m ycobacterial m embrane p rotein, l arge) family. Susceptibility was unaffected by the efflux pump inhibitors reserpine, carbonylcyanide m -chlorophenylhydrazone, and verapamil. Uptake/efflux experiments with [ 14 C]BM212 demonstrated that resistance is not driven by the efflux of BM212. Together, these data strongly suggest that the MmpL3 protein is the cellular target of BM212.
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Cites
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Advances in the development of new tuberculosis drugs and treatment regimens
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Self-citationMycolic Acids: Structures, Biosynthesis, and Beyond
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Crystal Structures of Membrane Transporter MmpL3, an Anti-TB Drug Target
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Metadata
- Authors
- La Rosa, V., Poce, G., Canseco, J. O., Buroni, S., Pasca, M. R., Biava, M., Raju, R. M., Porretta, G. C., Alfonso, S., Battilocchio, C., Javid, B., Sorrentino, F., Ioerger, T. R., Sacchettini, J. C., Manetti, F., Botta, M., De Logu, A., Rubin, E. J., & De Rossi, E.
- Venue
- Antimicrobial Agents and Chemotherapy
- Publisher
- American Society for Microbiology
- Published
- 2012-01
- Volume
- 56
- Issue
- 1
- Pages
- 324-331
- ISSN
- 0066-4804 (ISSN-L)
- 1098-6596
- OpenAlex
- W2005036750
- Cited by
- 212
- References
- 3
- FWCI
- 9.41
- Type
- journal article
- Language
- en
- Open access
- bronze
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- La Rosa, V., Poce, G., Canseco, J. O., Buroni, S., Pasca, M. R., Biava, M., Raju, R. M., Porretta, G. C., Alfonso, S., Battilocchio, C., Javid, B., Sorrentino, F., Ioerger, T. R., Sacchettini, J. C., Manetti, F., Botta, M., De Logu, A., Rubin, E. J., & De Rossi, E. (2012). MmpL3 Is the Cellular Target of the Antitubercular Pyrrole Derivative BM212. Antimicrobial Agents and Chemotherapy. https://doi.org/10.1128/aac.05270-11
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
