Microbial Bioactives
Microbial Bioactives | Online ISSN 2209-2161
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Volume 4 Number 1 2021
REVIEWS (Open Access)
Beyond Conventional Antibiotics: Emerging Peptide-Based, Host-Directed, and Repurposed Therapeutic Strategies Against Tuberculosis and Nontuberculous Mycobacterial Infections
Betty Fitriyasti 1*, Heng Yen Khong 2*
Microbial Bioactives 4 (1) 1-8 https://doi.org/10.25163/microbbioacts.4110713
Submitted: 15 May 2021 Revised: 08 July 2021 Accepted: 16 July 2021 Published: 18 July 2021
Abstract
Tuberculosis (TB) and nontuberculous mycobacterial (NTM) infections continue to challenge modern medicine in ways that feel both familiar and increasingly complex. Although conventional anti-tuberculosis therapies have saved millions of lives, the steady rise of multidrug-resistant and extensively drug-resistant strains has exposed the limitations of prolonged antibiotic-dependent regimens. At the same time, the growing prevalence of NTM infections, particularly among immunocompromised and elderly populations, has intensified the search for alternative therapeutic strategies. This systematic review explores emerging interventions that move beyond traditional antibiotics, with particular attention to antimicrobial peptides, lasso peptides, host-directed therapies, drug repurposing, and natural product-derived compounds. Evidence synthesized from preclinical, translational, and clinical studies suggests that engineered peptide therapeutics such as lassomycin and ecumicin demonstrate remarkable antimycobacterial potency through disruption of proteostatic and membrane-associated pathways. Meanwhile, host-directed approaches including metformin, vitamin D, and chloroquine adjunctive therapies appear to enhance macrophage-mediated bacterial clearance and immune modulation. Advances in nanoparticle delivery systems and metal–peptide complexes further improve therapeutic stability and intracellular targeting. Although heterogeneity and translational barriers remain substantial, the collective findings suggest that integrated multi-modal strategies may offer a more adaptable and resilient framework for combating TB and NTM diseases in the era of antimicrobial resistance.
Keywords: Tuberculosis; nontuberculous mycobacteria; antimicrobial peptides; host-directed therapy; multidrug resistance; drug repurposing; peptide therapeutics
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