Targeting Drug-Resistant Tuberculosis with Antimicrobial Peptides: Opportunities and Challenges

INTRODUCTION: One of the main causes of infectious disease-related deaths globally is Mycobacterium tuberculosis (M.tb), the causative agent of tuberculosis (TB). Novel treatment strategies are now much more urgent due to the emergence of Extensively Drug-Resistant (XDR) and multidrug-resistant (MDR) strains. The purpose of this study is to investigate the potential of antimicrobial peptides (AMPs) as TB adjunctive therapeutic agents, with an emphasis on their immunomodulatory and direct antimycobacterial effects. METHODS: A summary of how antimicrobial peptides (AMPs) work was carried out, including how they can damage bacterial membranes and obstruct intracellular processes. Furthermore, the review evaluated how AMPs affect host immune responses, including enhanced phagosome-lysosome fusion, induction of autophagy, and cytokine production. RESULTS: Many AMPs have shown strong antimycobacterial activity in vitro and in vivo, including defensins, cathelicidins (like LL-37), and synthetic analogues. Even with these encouraging outcomes, issues such as peptide stability and efficient delivery still stand in the way of clinical use. Potential remedies for these restrictions are offered by advances in peptide engineering, nanoparticle- based delivery methods, and structure-activity relationship (SAR) research. DISCUSSION: Recent advances in peptide engineering, nanoparticle-based delivery systems, and structure-activity relationship (SAR) studies offer promising strategies to overcome the limitations associated with AMP stability, bioavailability, and targeted delivery. These developments significantly enhance the translational potential of AMPs for TB therapy. CONCLUSION: Because of their distinct mechanisms of action and capacity to overcome drug resistance, AMPs offer a novel and promising approach to the treatment of tuberculosis. Global TB control efforts could be greatly aided by ongoing research into maximizing their safety and effectiveness.