Lecture
MS imaging in drug development: The clinical-stage antibiotic BTZ‑043 accumulates and efficiently acts against Mycobacterium tuberculosis in murine tuberculosis lesions
- at -
- ICM Saal 4b
- Type: Lecture
Lecture description
A. Römpp, Bayreuth/D, A. Treu, Bayreuth/D, J. Kokesch-Himmelreich, Bayreuth/D, F. Marwitz, Borstel/D, N. Aboutara, Borstel/D, L. Gröschel, Bayreuth/D, D. Schwudke, Borstel/D, M. Hoelscher, München/D, C. Hölscher, Borstel/D, K. Walter, Borstel/D
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), affects about 10 million people globally each year and was responsible for 1.3 million deaths in 2022. The development of drug resistance in Mtb calls for the development of novel antibiotics. These new anti-TB therapies need to effectively penetrate the cellular and necrotic compartments of tuberculosis lesions and reach sufficient concentrations to eliminate Mtb. MS imaging is the only technique that can provide detailed information about the penetration process and accumulation behavior of drugs in affected tissue. In the framework of the German Center for Infection Research (DZIF) we have developed a platform for an improved and accelerated evaluation of novel anti-TB drug candidates.
BTZ-043 is a novel antibiotic which is being developed within the DZIF network. It showed good bactericidal activity in humans in a phase IIa trial. High-resolution MALDI imaging revealed that BTZ-043 diffuses and accumulates in the cellular compartment, and fully penetrates the necrotic center. In addition, we report on lesional BTZ-043 concentrations severalfold above the minimal inhibitory concentration (MiC) and the substantial local efficacy of BTZ-043 in interleukin-13-overexpressing mice, which mimic human TB pathology of granuloma necrosis.
Our recent publication [1] 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. The results of this study will substantially influence the design of further clinical trials of several BTZ-043-based regimens which are currently prepared by the medical scientist within DZIF.
Literature:
[1] Römpp, A., A. Treu, J. Kokesch-Himmelreich, F. Marwitz, J. Dreisbach, N. Aboutara, D. Hillemann, M. Garrelts, P.J. Converse, S. Tyagi, S. Gerbach, L. Gyr, A.-K. Lemm, J. Volz, A. Hölscher, L. Gröschel, E.-M. Stemp, N. Heinrich, F. Kloss, E.L. Nuermberger, D. Schwudke, M. Hoelscher, C. Hölscher, and K. Walter. Nature Communications, 2025. 16(1): p. 826. 10.1038/s41467-025-56146-9
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb), affects about 10 million people globally each year and was responsible for 1.3 million deaths in 2022. The development of drug resistance in Mtb calls for the development of novel antibiotics. These new anti-TB therapies need to effectively penetrate the cellular and necrotic compartments of tuberculosis lesions and reach sufficient concentrations to eliminate Mtb. MS imaging is the only technique that can provide detailed information about the penetration process and accumulation behavior of drugs in affected tissue. In the framework of the German Center for Infection Research (DZIF) we have developed a platform for an improved and accelerated evaluation of novel anti-TB drug candidates.
BTZ-043 is a novel antibiotic which is being developed within the DZIF network. It showed good bactericidal activity in humans in a phase IIa trial. High-resolution MALDI imaging revealed that BTZ-043 diffuses and accumulates in the cellular compartment, and fully penetrates the necrotic center. In addition, we report on lesional BTZ-043 concentrations severalfold above the minimal inhibitory concentration (MiC) and the substantial local efficacy of BTZ-043 in interleukin-13-overexpressing mice, which mimic human TB pathology of granuloma necrosis.
Our recent publication [1] 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. The results of this study will substantially influence the design of further clinical trials of several BTZ-043-based regimens which are currently prepared by the medical scientist within DZIF.
Literature:
[1] Römpp, A., A. Treu, J. Kokesch-Himmelreich, F. Marwitz, J. Dreisbach, N. Aboutara, D. Hillemann, M. Garrelts, P.J. Converse, S. Tyagi, S. Gerbach, L. Gyr, A.-K. Lemm, J. Volz, A. Hölscher, L. Gröschel, E.-M. Stemp, N. Heinrich, F. Kloss, E.L. Nuermberger, D. Schwudke, M. Hoelscher, C. Hölscher, and K. Walter. Nature Communications, 2025. 16(1): p. 826. 10.1038/s41467-025-56146-9
