# RapTB: a lung-derived hemoglobin fragment with activity against Mycobacterium tuberculosis

## TL;DR

Researchers discovered a fragment of hemoglobin from human lung tissue, called RapTB, that can kill Mycobacterium tuberculosis, the bacteria that causes TB.

## Contribution

The study identifies RapTB, a lung-derived hemoglobin fragment, as a novel antimycobacterial agent with potential for host-directed TB therapy.

## Key findings

- RapTB inhibits extracellular Mycobacterium tuberculosis by up to 60% at 50 μM.
- Electron microscopy suggests RapTB disrupts the mycobacterial cell wall.
- RapTB is non-toxic to human macrophages but does not limit intracellular bacterial replication.

## Abstract

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 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.