The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Metformin as adjunct antituberculosis therapy
Abstract
The global burden of tuberculosis (TB) morbidity and mortality remains immense. A potential new approach to TB therapy is to augment protective host immune responses. We report that the antidiabetic drug metformin (MET) reduces the intracellular growth of Mycobacterium tuberculosis (Mtb) in an AMPK (adenosine monophosphate-activated protein kinase)-dependent manner. MET controls the growth of drug-resistant Mtb strains, increases production of mitochondrial reactive oxygen species, and facilitates phagosome-lysosome fusion. In Mtb-infected mice, use of MET ameliorated lung pathology, reduced chronic inflammation, and enhanced the specific immune response and the efficacy of conventional TB drugs. Moreover, in two separate human cohorts, MET treatment was associated with improved control of Mtb infection and decreased disease severity. Collectively, these data indicate that MET is a promising candidate host-adjunctive therapy for improving the effective treatment of TB.
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“For example, the anti-diabetic drug metformin is being utilized an immunomodulator for tuberculosis (Singhal et al., 2014).”
From Mitochondria in the Regulation of Innate and Adaptive Immunity (2015) · cites this paper as Singhal et al., 2014
Citations
Cites
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AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1
Kim, J., Kundu, M., Viollet, B., & Guan, K.-L. (2011) · Nature Cell Biology · doi:10.1038/ncb2152 · Cited by 7,227
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
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The AMPK signalling pathway coordinates cell growth, autophagy and metabolism
Mihaylova, M. M., & Shaw, R. J. (2011) · Nature Cell Biology · doi:10.1038/ncb2329 · Cited by 2,923
Gutierrez, M. G., Master, S. S., Singh, S. B., Taylor, G. A., Colombo, M. I., & Deretic, V. (2004) · Cell · doi:10.1016/j.cell.2004.11.038 · Cited by 2,252
OWEN, M. R., DORAN, E., & HALESTRAP, A. P. (2000) · Biochemical Journal · doi:10.1042/bj3480607 · Cited by 2,157
An interferon-inducible neutrophil-driven blood transcriptional signature in human tuberculosis
Berry, M. P. R., Graham, C. M., McNab, F. W., Xu, Z., Bloch, S. A. A., Oni, T., Wilkinson, K. A., Banchereau, R., Skinner, J., Wilkinson, R. J., et al. (2010) · Nature · doi:10.1038/nature09247 · Cited by 1,898
Cellular and molecular mechanisms of metformin: an overview
Viollet, B., Guigas, B., Garcia, N. S., Leclerc, J., Foretz, M., & Andreelli, F. (2012) · Clinical Science · doi:10.1042/cs20110386 · Cited by 1,720
Tlr signalling augments macrophage bactericidal activity through mitochondrial ros
West, A. P., Brodsky, I. E., Rahner, C., Woo, D. K., Erdjument-Bromage, H., Tempst, P., Walsh, M. C., Choi, Y., Shadel, G. S., & Ghosh, S. (2011) · Nature · doi:10.1038/nature09973 · Cited by 1,659
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Sorted by citations
Gut microbiota and intestinal FXR mediate the clinical benefits of metformin
Sun, L., Xie, C., Wang, G., Wu, Y., Wu, Q., Wang, X., Liu, J., Deng, Y., Xia, J., Chen, B., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0222-4 · Cited by 1,011
Mitochondria in the Regulation of Innate and Adaptive Immunity
Weinberg, S. E., Sena, L. A., & Chandel, N. S. (2015) · Immunity · doi:10.1016/j.immuni.2015.02.002 · Cited by 960
Arts, R. J. W., Novakovic, B., ter Horst, R., Carvalho, A., Bekkering, S., Lachmandas, E., Rodrigues, F., Silvestre, R., Cheng, S.-C., Wang, S.-Y., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.10.008 · Cited by 930
Host-directed therapies for bacterial and viral infections
Kaufmann, S. H. E., Dorhoi, A., Hotchkiss, R. S., & Bartenschlager, R. F. W. (2017) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.162 · Cited by 869
Metformin: update on mechanisms of action and repurposing potential
Foretz, M., Guigas, B., & Viollet, B. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00833-4 · Cited by 791
Metadata
- Authors
- Singhal, A., Jie, L., Kumar, P., Hong, G. S., Leow, M. K.-S., Paleja, B., Tsenova, L., Kurepina, N., Chen, J., Zolezzi, F., Kreiswirth, B., Poidinger, M., Chee, C., Kaplan, G., Wang, Y. T., & De Libero, G.
- Affiliations
- Agency for Science, Technology and Research (SG)
- Singapore Immunology Network, Agency for Science, Technology and Research (A*STAR), Singapore 138648, Singapore.
- Tan Tock Seng Hospital (SG)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Singhal, Amit
- Kumar, Pavanish
- ORCID
- Venue
- Science Translational Medicine
- Published
- 2014-11-19
- Volume
- 6
- Issue
- 263
- Pages
- 263ra159-263ra159
- ISSN
- 1946-6234 (ISSN-L)
- 1946-6242
- OpenAlex
- W2105296171
- Cited by
- 547
- References
- 49
- Citations by year
- 2026: 39 · 2025: 44 · 2024: 44 · 2023: 35 · 2022: 51 · 2021: 64 · 2020: 71 · 2019: 53 · 2018: 51 · 2017: 33 · 2016: 35 · 2015: 24 · 2014: 2
- FWCI
- 22.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science Translational Medicine (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- edoc (University of Basel) (submittedVersion)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Immunology and Microbiology › Immunology › Immune responses and vaccinations
- Health Sciences › Medicine › Infectious Diseases › Infectious Diseases and Tuberculosis
- Keywords
- metformin, tuberculosis, Mycobacterium tuberculosis, AMPK, host-directed therapy, drug-resistant tuberculosis, reactive oxygen species, phagosome-lysosome fusion, host immune response, chronic inflammation
- MeSH terms
- Humans, Metformin, Microbial Sensitivity Tests, Mycobacterium tuberculosis, Tuberculosis, Reactive Oxygen Species
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