ORIGINAL RESEARCH article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1613241
This article is part of the Research TopicAdvancements in Diversity and Drug Resistance Mechanisms in Mycobacterial DiseasesView all 9 articles
Antimycobacterial activity of the plectasin derivative NZ2114
Provisionally accepted- 1Lund University, Lund, Sweden
- 2Imperial College London, London, England, United Kingdom
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Mycobacteria have a unique hydrophobic membrane with several lipid-enriched layers that are low in permeability, setting them apart from other bacteria. This complex structure, consisting of three distinct layers is crucial for cell growth, virulence, and providing a barrier to antibiotics. Previously, we identified a plectasin variant, NZX, which showed activity against Mycobacterium tuberculosis in several murine tuberculosis (TB) infection studies and had a bactericidal effect against multi-drug resistant (MDR) M. tuberculosis at therapeutic concentrations. In this study, we investigated another plectasin variant, NZ2114, known for its effectiveness against Gram-positive bacteria, as a potential antimycobacterial peptide both in vitro and in vivo. NZ2114 effectively killed mycobacteria at a minimal inhibitory concentration (MIC99) of 6.1 µM, was non-toxic to primary human cells, and remained resistant to serum degradation while preserving its antimycobacterial capacity. In a checkerboard assay, NZ2114 demonstrated synergy with the first-line TB drugs isoniazid and ethambutol. The antimicrobial effect was also observed against several clinical isolates of Gram-positive bacteria, including Enterococcus faecalis, Enterococcus faecium, and Methicillin-Resistant Staphylococcus aureus (MRSA). In our murine TB infection model, compared to untreated controls, NZ2114 eliminated M. tuberculosis with a log reduction of 0.72 (81.14%) after three doses. These studies suggest NZ2114 as a potential TB therapy, aiding in the control of this significant infectious disease.
Keywords: Mycobacterium tuberculosis, Tuberculosis, Peptides, Plectasin, Treatment
Received: 17 Apr 2025; Accepted: 11 Jun 2025.
Copyright: © 2025 Godaly, Davids, Umashankar-Fransson, Krishnan and Robertson. 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: Gabriela Godaly, Lund University, Lund, Sweden
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