Publikationen 2025
RapTB: a lung-derived hemoglobin fragment with activity against Mycobacterium tuberculosis
Leonard Klevesath1,2, Reiner Noschka1,2, Thomas Vomhof3, Jacky Mohnani1,2, Mark Grieshober1,2, Jens Michaelis3, Paul Walther4,5, Armando Rodriguez6,7, Nico Preising6, Clarissa Read5, Sebastian Wiese6, Ludger Ständker7, Dietmar R. Thal8, Jan Münch4,9 and Steffen Stenger1,2,4
1Ulm University Medical Center, Ulm, Germany, 2Institut of Medical Microbiology and Hygiene, Medical Facility, Ulm University, Ulm, Germany, 3Institute of Biophysics, Ulm University, Ulm, Germany, 4University of Ulm, Ulm, Germany, 5Central Facility for Electron Microscopy, Ulm University, Ulm, Germany, 6Core Unit Mass Spectrometry and Proteomics, Ulm, Germany, 7Core Facility of Functional Peptidomics, Ulm University, Ulm, Germany, 8Laboratory of Neuropathology, Department of Imaging and Pathology, Leuven Brain Institute, KU- Leuven, Leuven, Belgium, 9Institut of Molecular Virology, Ulm University, Ulm, Germany
Tuberculosis (TB) remains difficult to treat due to the need for prolonged multidrug therapy and the global rise of drug-resistant Mycobacterium tuberculosis (Mtb) strains. Endogenous antimicrobial peptides (AMPs) have emerged as promising candidates for host-directed therapies. Given the pulmonary nature of TB, we hypothesized that human lung tissue contains peptides with intrinsic antimycobacterial activity. We screened a peptide library derived from human lung tissue and identified a 39-amino-acid C-terminal fragment of β-hemoglobin (HBB(112–147)), referred to as RapTB, with potent activity against Mtb. Recombinant RapTB exhibited dosedependent inhibition of extracellular Mtb, reaching ~60% activity at 50 μM. Electron microscopy revealed mycobacterial cell wall disruption as a likely mechanism. RapTB was non-toxic to primary human macrophages and efficiently internalized by Mtb-infected cells. However, it did not co-localize with intracellular bacilli and failed to limit intracellular replication. HBB-derived fragments such as RapTB have previously been identified in human tissues and are known to exhibit broadspectrum antimicrobial activity. Our findings extend this functional class to include antimycobacterial activity and suggest a potential role for RapTB in the early, extracellular phase of host defense against TB.
https://www.frontiersin.org/articles/10.3389/fmicb.2025.1669022