Antimicrobial Peptides as Novel Therapeutics: An In-depth Exploration into Mechanisms, Resistance Challenges, and Clinical Prospects

Abstract

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Antimicrobial peptides (AMPs) play a crucial part in innate immunity. They are naturally occurring, short-chain peptides. Furthermore, they show a broad-spectrum of activity against a variety of bacteria and viruses, along with immunomodulatory effects. This dual therapeutic potential has raised researchers’ interest as an alternative to antibiotics. The majority of antimicrobials available in the market encounter resistance considerably. Whereas resistance of AMPs is subordinate due to their unique mechanism of action. In spite of such benefits, clinical translation of AMPs is still a challenge owing to their high manufacturing cost, toxicity, proteolytic instability, and microbial resistance. Current advancements in chemical modifications, peptide engineering, and nano delivery have emerged to address such challenges. The current study aimed to provide a comprehensive insight into resistance pathways, therapeutic applications, cellular mechanisms, critical analysis of in-progress clinical trials, structural features, and future perspectives. AMPs depicted significant interactions that modulate cytokine production, chemotaxis, and immune responses. This validates the role of AMPs as immune sentinels, regulating both adaptive and innate immunity, unlike usual antimicrobials. The key objective of this study was to explicate the organ level defensive role of AMPs in a comprehensive manner. Moreover, the study also explored multiple bacterial resistance tactics. Recent approaches, such as nano-carrier drug delivery systems, peptide engineering, and backbone modifications, enhanced evasion, tissue targeting and bioavailability of AMPs have also been traversed. By accentuating both opportunities and challenges, this study focused on the possible translational potential of AMPs in tackling the antimicrobial resistance (AMR) dilemma worldwide.