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Römpp, A.* ; Treu, A.* ; Kokesch-Himmelreich, J.* ; Marwitz, F.* ; Dreisbach, J.* ; Aboutara, N.* ; Hillemann, D.* ; Garrelts, M.* ; Converse, P.J.* ; Tyagi, S.* ; Gerbach, S.* ; Gyr, L.* ; Lemm, A.K.* ; Volz, J.* ; Hölscher, A.* ; Gröschel, L.* ; Stemp, E.M.* ; Heinrich, N.* ; Kloss, F.* ; Nuermberger, E.L.* ; Schwudke, D.* ; Hoelscher, M. ; Hölscher, C.* ; Walter, K.*

The clinical-stage drug BTZ-043 accumulates in murine tuberculosis lesions and efficiently acts against Mycobacterium tuberculosis.

Nat. Commun. 16:826 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The development of granulomas with central necrosis harboring Mycobacterium tuberculosis (Mtb) is the hallmark of human tuberculosis (TB). New anti-TB therapies need to effectively penetrate the cellular and necrotic compartments of these lesions and reach sufficient concentrations to eliminate Mtb. BTZ-043 is a novel antibiotic showing good bactericidal activity in humans in a phase IIa trial. Here, we report on lesional BTZ-043 concentrations severalfold above the minimal-inhibitory-concentration and the substantial local efficacy of BTZ-043 in interleukin-13-overexpressing mice, which mimic human TB pathology of granuloma necrosis. High-resolution MALDI imaging further reveals that BTZ-043 diffuses and accumulates in the cellular compartment, and fully penetrates the necrotic center. This is the first study that visualizes an efficient penetration and accumulation of a clinical-stage TB drug in human-like centrally necrotizing granulomas and that also determines its lesional activity. Our results most likely predict a substantial bactericidal effect of BTZ-043 at these hard-to-reach sites in TB patients.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter High-resolution; Antituberculosis Drugs; Sterilizing Activity; Mass; Benzothiazinones; Heterogeneity; Model; Dpre1; Microenvironments; Quantification
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 16, Heft: 1, Seiten: , Artikelnummer: 826 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Global Health (UGH)
Förderungen German Research Foundation
Leibniz Center for Photonics in Infection Research
German Federal Ministry of Education (BMBF) via the German Center of Infection Research (DZIF)