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Every year, 10 million people contract tuberculosis (TB). Around 1.5 million patients succumb to the disease caused by the bacterium Mycobacterium tuberculosis (Mtb). The novel antibiotic BTZ-043 has shown good bactericidal activity in human clinical trials. In a study recently published in the journal Nature Communications, DZIF scientists led by the University of Bayreuth and the Research Center Borstel, Leibniz Lung Center were able to show that BTZ-043 effectively penetrates TB lesions, accumulates there in high concentrations and can thus fight the Mtb bacteria even in hard-to-reach areas.
Every year, 10 million people contract tuberculosis (TB), a disease caused by the bacterium Mycobacterium tuberculosis (Mtb), and approximately 1.5 million patients succumb to the disease. Treatment of TB usually requires several months of antibiotic therapy, but the rise of drug-resistant forms of TB has led to an urgent need for new drugs. The novel antibiotic BTZ-043, developed jointly by researchers at the German Center for Infection Research (DZIF), the Institute for Infectious Diseases and Tropical Medicine (Tropical Institute) at the LMU University Hospital Munich and the Leibniz Institute for Natural Product Research and Infection Biology – Hans Knöll Institute (Leibniz-HKI) in Jena, has shown good bactericidal activity in human clinical trials. In a study recently published in the renowned journal Nature Communications, DZIF scientists led by the University of Bayreuth and the Research Center Borstel, Leibniz Lung Center—in collaboration with Leibniz-HKI, the Tropical Institute Munich and Johns Hopkins University—made important progress in the research of this drug. They were able to show that BTZ-043 effectively penetrates TB lesions and accumulates there in high concentrations. Consequently, the drug can fight Mtb bacteria even in hard-to-reach areas.
A characteristic feature of tuberculosis (tubercle = nodular swelling) is the formation of granulomas. These nodular tissue changes are formed by the body in the lungs to twall off and contain Mtb bacteria. Granulomas are composed of a fibrous capsule which surrounds a layer of immune cells and a core of dead tissue (necrotic core) where the bacteria can hide and survive. These necrotic areas pose a particular challenge as they are poorly supplied with blood, making it difficult for antibiotics to reach them. Using a mouse model that reflects the TB pathology of granuloma necrosis in humans, the DZIF research team demonstrated the remarkable ability of the new antibiotic BTZ-043 to efficiently penetrate, accumulate and reduce the bacterial load in these necrotic granulomas.
The researchers exploited an advanced mouse model in which a genetic modification causes the development of granulomas in these animals similar to those found in TB patients. In a landmark study using these mice, recently published in Nature Communications, the researchers demonstrated that the concentration of BTZ-043 in the lesions was many times higher than the minimum concentration required to effectively combat Mtb.
High-resolution MALDI mass spectrometry also revealed the unique ability of BTZ-043 to penetrate deep into the cellular compartments of the lesions and completely penetrate the necrotic centers.
"Our study represents an important step in the development of new tuberculosis antibiotics, as we were able—for the first time—to visualize the distribution of a clinical-stageTB drug under development in the granuloma," says DZIF scientist Prof. Andreas Römpp from the University of Bayreuth, Chair of Bioanalytical Sciences and Food Analysis, first author and corresponding author of the study.
"The ability of BTZ-043 to reach and act in these hard-to-reach lesions indicates a strong bactericidal effect that could make tuberculosis therapy more efficient," adds corresponding last author and DZIF scientist Dr. Kerstin Walter from the Research Center Borstel, Leibniz Lung Center.
The development of this advanced mouse model, which in contrast to many commonly used mouse models recapitulates the pathology of human tuberculosis very well, is a milestone in the search for new antibiotics against tuberculosis," adds Dr. Christoph Hölscher, research group leader at the Research Center Borstel, Leibniz Lung Center and coordinator of the central theme "New Drugs and Regimens" in the DZIF research area "Tuberculosis".
"These findings are promising for the millions of people suffering from tuberculosis worldwide and offer a glimpse of a future in which less accessible tuberculosis lesions can be reached with another drug. As research progresses, the potential of BTZ-043 to improve clinical outcomes for tuberculosis patients becomes clearer," says Dr. Julia Dreisbach, Scientific Program Manager for BTZ-043 at the Tropical Institute Munich.
The work was funded by the Federal Ministry of Education and Research (BMBF) in the framework of the German Center for Infection Research (DZIF). The researchers would like to thank their colleagues at the Research Center Borstel, Leibniz Lung Center for organizing the animal husbandry and for their support in carrying out the experiments. Further thanks go to Hapila GmbH, Gera, who produces BTZ-043 and provides all analytical standards for the LMU University Hospital Munich and Leibniz-HKI.
Prof. Dr. Andreas Römpp
Universität Bayreuth
Andreas.Roempp@uni-bayreuth.de
Dr. Kerstin Walter
Forschungszentrum Borstel, Leibniz Lungenzentrum
kwalter@fz-borstel.de
Römpp, A., Treu, A., Kokesch-Himmelreich, J. et al. The clinical-stage drug BTZ-043 accumulates in murine tuberculosis lesions and efficiently acts against Mycobacterium tuberculosis. Nat Commun 16, 826 (2025). https://doi.org/10.1038/s41467-025-56146-9
https://www.dzif.de/en/novel-antibiotic-btz-043-also-reaches-tuberculosis-bacter... Press release of the German Center for Infection Research (DZIF)
Granuloma structure and distribution of the antibiotic BTZ-043 in differently stained tissue section ...
CC BY 4.0/Images modified from: Römpp, A. et al. The clinical-stage drug BTZ-043 accumulates
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Granuloma structure and distribution of the antibiotic BTZ-043 in differently stained tissue section ...
CC BY 4.0/Images modified from: Römpp, A. et al. The clinical-stage drug BTZ-043 accumulates
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