ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Infectious Agents and Disease
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1669022
This article is part of the Research TopicMechanisms and Innovations in Combating Intracellular InfectionsView all 7 articles
RapTB: A Lung-Derived Hemoglobin Fragment with activity against Mycobacterium tuberculosis
Provisionally accepted
Leonard Raphael Klevesath1,2*
Reiner Noschka2,3
Thomas Vomhof4
Jacky Mohnani2,5
Mark Grieshober2,5
Jens Michaelis6
Paul Walther3,7
Armando A. Rodríguez Alfonso4,8
Nico Preising4
Clarissa Read7
Sebastian Wiese4
Ludger Staendker8
Dietmar R Thal9
Jan Muench10,3
Steffen Stenger2,5- 1University of Ulm, Ulm, Germany
- 2Universitatsklinikum Ulm Institut fur Medizinische Mikrobiologie und Hygiene, Ulm, Germany
- 3Universitat Ulm, Ulm, Germany
- 4Core Unit Mass Spectrometry and Proteomics, Ulm, Germany
- 5Universitatsklinikum Ulm, Ulm, Germany
- 6Institut of Biophysics, Ulm, Germany
- 7Central Facility for Electron Microscopy, Ulm, Germany
- 8Core Facility of Functional Peptidomics, Ulm, Germany
- 9Institut of Neuropathology, Leuven, Belgium
- 10Institut of Molecular Virology, Ulm, Germany
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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 (1). 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 dose-dependent 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 broad-spectrum 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.
Keywords: Tuberculosis 1, antimicrobial peptides 2, Human 3, lung 4, endogenous peptide 5
Received: 18 Jul 2025; Accepted: 03 Oct 2025.
Copyright: © 2025 Klevesath, Noschka, Vomhof, Mohnani, Grieshober, Michaelis, Walther, Rodríguez Alfonso, Preising, Read, Wiese, Staendker, Thal, Muench and Stenger. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Leonard Raphael Klevesath, raphaelklevesath@yahoo.de
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.