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Dimethyl fumarate eliminates differentially culturable Mycobacterium tuberculosis in an intranasal murine model of tuberculosis

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journal contribution
posted on 2022-11-15, 14:58 authored by SM Glenn, O Turapov, V Makarov, DB Kell, GV Mukamolova

Tuberculosis (TB) claims nearly 1.5 million lives annually. Current TB treatment requires a combination of several drugs administered for at least 6 months. Mycobacterium tuberculosis (Mtb), the causative agent of TB, can persist in infected humans and animals for decades. Moreover, during infection, Mtb produces differentially culturable bacteria (DCB) that do not grow in standard media but can be resuscitated in liquid media supplemented with sterile Mtb culture filtrates or recombinant resuscitation-promoting factors (Rpfs). Here, we demonstrate that, in an intranasal murine model of TB, Mtb DCB are detectable in the lungs after 4 weeks of infection, and their loads remain largely unchanged during a further 8 weeks. Treatment of the infected mice with dimethyl fumarate (DMF), a known drug with immunomodulatory properties, for 8 weeks eliminates Mtb DCB from the lungs and spleens. Standard TB treatment consisting of rifampicin, isoniazid, and pyrazinamide for 8 weeks reduces Mtb loads by nearly four orders of magnitude but does not eradicate DCB. Nevertheless, no DCB can be detected in the lungs and spleens after 8 weeks of treatment with DMF, rifampicin, isoniazid, and pyrazinamide. Our data suggest that addition of approved anti-inflammatory drugs to standard treatment regimens may improve TB treatment and reduce treatment duration.

Funding

Leicester – Confidence in Concept 2019

Medical Research Council

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Russian Science Foundation under grant 21-15-00042

History

Author affiliation

Division of Biomedical Services, University of Leicester

Version

  • VoR (Version of Record)

Published in

Frontiers in Cellular and Infection Microbiology

Volume

12

Pagination

957287

Publisher

Frontiers Media SA

issn

2235-2988

eissn

2235-2988

Copyright date

2022

Available date

2022-11-15

Spatial coverage

Switzerland

Language

eng

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