Metformin as adjunct antituberculosis therapy

Singhal, Amit and Jie, Liu and Kumar, Pavanish and Hong, Gan suay and Leow, Melvin Khee and Paleja, Bhairav and Tsenova, Liana and Kurepina, Natalia and Chen, Jinmiao and Zolezzi, Francesca and Kreiswirth, Barry N. and Poidinger, Michael and Chee, Cynthia and Kaplan, Gilla and Wang, Yee Tang and De Libero, Gennaro. (2014) Metformin as adjunct antituberculosis therapy. Science Translational Medicine, 6 (263). 263ra159.

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Official URL: https://edoc.unibas.ch/61651/

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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.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Experimental Immunology (De Libero)
UniBasel Contributors:De Libero, Gennaro
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:American Association for the Advancement of Science
Note:Publication type according to Uni Basel Research Database: Journal article
Identification Number:
Last Modified:20 Jul 2020 15:43
Deposited On:20 Jul 2020 15:43

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