Microbial Bioactives
Microbial Bioactives | Online ISSN 2209-2161
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Volume 4 Number 1 2021
REVIEWS (Open Access)
Next-Generation Therapeutics for Tuberculosis and Nontuberculous Mycobacterial Infections: Antimicrobial Peptides, Host-Directed Strategies, and Overcoming Drug Resistance
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 remain formidable global health challenges, exacerbated by rising multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Conventional antibiotics, although effective against drug-susceptible strains, face limitations due to prolonged treatment durations, host toxicity, and intrinsic mycobacterial defenses, including a lipid-rich cell envelope and intracellular persistence. Emerging therapeutic strategies aim to transcend these limitations by exploring novel antimicrobial modalities, host-directed therapies (HDT), and drug repurposing approaches. Antimicrobial peptides (AMPs), both natural and engineered, exhibit broad-spectrum activity against mycobacteria and can enhance host immune mechanisms such as autophagy and phagosomal maturation. Lasso peptides, acyldepsipeptides, and cyclic natural products target essential proteostatic machinery, including Clp protease complexes, highlighting the potential of proteostasis disruption as a therapeutic avenue. Advances in natural product discovery, exemplified by teixobactin and alkaloid derivatives, offer additional scaffolds for antimycobacterial drug development. Complementary strategies, including nanoparticle-based delivery systems, metal–peptide complexes, and host immune modulation, aim to optimize bioavailability and reduce toxicity. Concurrently, rapid diagnostics and immunological assays improve detection and treatment monitoring, enhancing clinical outcomes. This systematic review synthesizes current evidence on innovative mycobacterial therapeutics, emphasizing integration of antimicrobial discovery, host-targeted strategies, and translational approaches. By moving beyond conventional antibiotics, these multifaceted interventions hold promise for mitigating global TB and NTM disease burdens and addressing drug resistance challenges.
Keywords: Mycobacterium tuberculosis, nontuberculous mycobacteria, antimicrobial peptides, host-directed therapy, drug repurposing, multidrug resistance, novel therapeutics
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