Glenn, Sarah M, Turapov, Obolbek, Makarov, Vadim, Kell, Douglas B 
ORCID: 0000-0001-5838-7963 and Mukamolova, Galina V
(2022)
Dimethyl fumarate eliminates differentially culturable <i>Mycobacterium tuberculosis</i> in an intranasal murine model of tuberculosis.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY, 12.
957287-.
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Dimethyl fumarate eliminates differentially culturable iMycobacterium tuberculosisi in an intranasal murine model of tubercu.pdf - Published version Download (848kB) | Preview |
Abstract
Tuberculosis (TB) claims nearly 1.5 million lives annually. Current TB treatment requires a combination of several drugs administered for at least 6 months. <i>Mycobacterium tuberculosis</i> (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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Mycobacterium tuberculosis, tuberculosis, differentially culturable bacteria, treatment, persisters, resuscitation-promoting factor, dimethyl fumarate |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 12 Oct 2022 08:23 |
| Last Modified: | 08 Oct 2023 15:18 |
| DOI: | 10.3389/fcimb.2022.957287 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3165387 |
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