Cited by 548Tuberculosis Research and EpidemiologyImmune responses and vaccinationsInfectious Diseases and Tuberculosis

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Metformin as adjunct antituberculosis therapy

Singhal, Amit, Jie, Liu, Kumar, Pavanish, Hong, Gan Suay, Leow, Melvin Khee-Shing, Paleja, Bhairav, Tsenova, Liana, Kurepina, Natalia, Chen, Jinmiao, Zolezzi, Francesca, Kreiswirth, Barry, Poidinger, Michael, Chee, Cynthia, Kaplan, Gilla, Wang, Yee Tang, De Libero, Gennaro·2014·Science Translational Medicine

DOI 10.1126/scitranslmed.3009885

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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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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: Singhal, Amit
Kumar, Pavanish
Leow, Melvin Khee-Shing
Paleja, Bhairav
Chen, Jinmiao
Zolezzi, Francesca
Kreiswirth, Barry
Poidinger, Michael
Chee, Cynthia
Venue: Science Translational Medicine
Publisher: American Association for the Advancement of Science (AAAS)
Published: 2014-11-19
Volume: 6
Issue: 263
Pages: 263ra159-263ra159
ISSN: 1946-6234 (ISSN-L)
1946-6242
DOI: 10.1126/scitranslmed.3009885
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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