The DOI matches its Crossref record; 62 of the 62 references it cites were found in a registry or an index.
Drug Tolerance in Replicating Mycobacteria Mediated by a Macrophage-Induced Efflux Mechanism
Open accessAbstract
SUMMARY Treatment of tuberculosis, a complex granulomatous disease, requires long-term multidrug therapy to overcome tolerance, an epigenetic drug resistance that is widely attributed to nonreplicating bacterial subpopulations. Here, we deploy Mycobacterium marinum-infected zebrafish larvae for in vivo characterization of antitubercular drug activity and tolerance. We describe the existence of multi-drug tolerant organisms that arise within days of infection, are enriched in the replicating intracellular population, and are amplified and disseminated by the tuberculous granuloma. Bacterial efflux pumps that are required for intracellular growth mediate this macrophage-induced tolerance. This newly discovered tolerant population also develops when Mycobacterium tuberculosis infects cultured macrophages, suggesting that it contributes to the burden of drug tolerance in human tuberculosis. Efflux pump inhibitors like verapamil reduce this tolerance. Thus, the addition of this currently approved drug, or more specific inhibitors, to standard antitubercular therapy may shorten the duration of curative treatment.
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Cited by
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Internalization of Salmonella by Macrophages Induces Formation of Nonreplicating Persisters
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Metadata
- Authors
- Adams, K. N., Takaki, K., Connolly, L. E., Wiedenhoft, H., Winglee, K., Humbert, O., Edelstein, P. H., Cosma, C. L., & Ramakrishnan, L.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 145
- Issue
- 1
- Pages
- 39-53
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2093178459
- Cited by
- 530
- References
- 62
- FWCI
- 26.83
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Adams, K. N., Takaki, K., Connolly, L. E., Wiedenhoft, H., Winglee, K., Humbert, O., Edelstein, P. H., Cosma, C. L., & Ramakrishnan, L. (2011). Drug Tolerance in Replicating Mycobacteria Mediated by a Macrophage-Induced Efflux Mechanism. Cell. https://doi.org/10.1016/j.cell.2011.02.022
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