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Antimicrobial Peptides as Immunomodulators and Antimycobacterial Agents to Combat Mycobacterium tuberculosis: a Critical Review

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Abstract

Tuberculosis (TB) is a devastating disease foisting a significantly high morbidity, prepotent in low- and middle-income developing countries. Evolution of drug resistance among Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, has made the TB treatment more complicated. The protracted nature of present TB treatment, persistent and tolerant Mtb populations, interaction with antiretroviral therapy and existing toxicity concerned with conventional anti-TB drugs are the four major challenges inflicted with emergence of drug-resistant mycobacterial strains, and the standard medications are unable to combat these strains. These factors emphasize an exigency to develop new drugs to overcome these barriers in current TB therapy. With this regard, antimycobacterial peptides derived from various sources such as human cells, bacterial sources, mycobacteriophages, fungal, plant and animal sources could be considered as antituberculosis leads as most of these peptides are associated with dual advantages of having both bactericidal activity towards Mtb as well as immuno-regulatory property. Some of the peptides possess the additional advantage of interacting synergistically with antituberculosis medications too, thereby increasing their efficiency, underscoring the vigour of antimicrobial peptides (AMPs) as best possible alternative therapeutic candidates or adjuvants in TB treatment. Albeit the beneficiary features of these peptides, few obstacles allied with them like cytotoxicity and proteolytic degradation are matter of concerns too. In this review, we have focused on structural hallmarks, targeting mechanisms and specific structural aspects contributing to antimycobacterial activity and discovered natural and synthetic antimycobacterial peptides along with their sources, anti-TB, immuno-regulatory properties, merits and demerits and possible delivery methods of AMPs.

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Acknowledgements

The authors would like to thank the management of VIT, Vellore Institute of Technology (VIT), Vellore, for providing the necessary facilities to carry the work. The authors sincerely thank Dr. Sudha Ramaiah, VIT, Vellore, for her support throughout the work. Preethi A. R. would like to extend her thanks to scholars of Medical and Biological Computing Laboratory, School of Biosciences and Technology, VIT, Vellore, Ms. P. Priyamvada for her immense help to format the article in a presentable way, Mr. Aniket Naha for his suggestions to improve the manuscript, Mr. Soumya Basu for his inputs and guidance, Ms. Reetika Debroy, Ms. Gayathri Ashok and Mr. Hithesh Kumar C. K. for their constant encouragement in each and every aspect.

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Preethi A. R.: conceptualization, writing — review and editing. Anand Anbarasu: conceptualization, validation, visualization, supervision.

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R., P.A., Anbarasu, A. Antimicrobial Peptides as Immunomodulators and Antimycobacterial Agents to Combat Mycobacterium tuberculosis: a Critical Review. Probiotics & Antimicro. Prot. 15, 1539–1566 (2023). https://doi.org/10.1007/s12602-022-10018-6

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