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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
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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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