PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
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.
Impact Factor
Scopus SNIP
Altmetric
15.700
0.000
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter High-resolution; Antituberculosis Drugs; Sterilizing Activity; Mass; Benzothiazinones; Heterogeneity; Model; Dpre1; Microenvironments; Quantification
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
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
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Global Health (UGH)
POF Topic(s) 30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) G-540001-003
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)
DOI 10.1038/s41467-025-56146-9
WOS ID 001400571200017
Scopus ID 85216439865
PubMed ID 39827265
Erfassungsdatum 2025-03-24
[➜Korrektur melden]