Peptide-Based Strategies Against <i>Mycobacterium tuberculosis</i> Covering Immunomodulation, Vaccines, Synergistic Therapy, and Nanodelivery.
Roque-Borda. Cesar Augusto CA; Vishwakarma. Subham Kumar SK; Ramirez Delgado. Oswaldo Julio OJ; de Souza Rodrigues. Heitor Leocadio HL; Primo. Laura M D LMD; Campos. Isabella Cardeal IC; de Lima. Tulio Spina TS; Perdigão. João J; Pavan. Fernando Rogério FR
Key Findings
- Vitamin D can trigger the body to make more LL‑37, an antimicrobial peptide that helps fight TB.
- LL‑37 and similar peptides can be combined with standard TB medicines to improve their killing power, especially against drug‑resistant strains.
- Advanced delivery methods like inhalable nanocarriers can protect peptides and get them straight to the lungs where TB lives.
Practical Outcomes
- For most biohackers, the review offers limited direct actions. The most relevant take‑away is that maintaining adequate vitamin D might modestly boost LL‑37 levels, but there’s no proven protocol for using LL‑37 itself outside clinical settings. The nanodelivery and vaccine concepts are still experimental and not ready for DIY use.
Summary
The paper reviews how small proteins called antimicrobial peptides, especially LL‑37, might help fight tuberculosis by boosting the immune system, working together with existing TB drugs, and being delivered directly to the lungs using nanotech. It’s mostly a scientific overview, not a how‑to guide for personal use.
Abstract
Tuberculosis (TB), caused by <i>Mycobacterium tuberculosis</i> (MTB), remains one of the most devastating infectious diseases worldwide, with rising multidrug resistance limiting the effectiveness of conventional treatments. Novel therapeutic approaches are urgently needed to complement or replace existing regimens. Among emerging candidates, antimicrobial peptides (AMPs) stand out as versatile molecules capable of exerting direct antimycobacterial effects while also modulating the host immune response. This review explores peptide-based strategies against TB, with a focus on four major axes of innovation. First, we examine host-directed pathways, including the vitamin D-cathelicidin axis and other immunomodulatory mechanisms and their regulatory role in the induction of endogenous AMPs such as cathelicidin LL-37, which contributes to host-directed defense. Second, we discuss peptide-based vaccines designed to elicit robust and durable protective immunity, representing a complementary alternative to classical vaccine approaches. Third, we highlight the synergistic potential of AMPs in combination with first-line and second-line anti-TB drugs, aiming to restore or enhance bactericidal activity against resistant strains. Finally, we analyze technological platforms, including nanocarriers and inhalable formulations, that enable targeted pulmonary delivery, improve peptide stability, and enhance bioavailability. By integrating molecular design, immune modulation, and advanced delivery systems, peptide-based strategies provide a multifaceted approach to overcoming the limitations of current TB therapy. Collectively, these advances position AMPs not only as promising standalone agents but also as key components in combination and host-directed therapies, with strong potential to reshape the future clinical management of tuberculosis.
Study Information
pubmed
2025
2025-09-25T00:00:00.000Z
10.3390/ph18101440
2
237