Antimicrobial peptides for tuberculosis in a post-antibiotic era: from in vitro promise to therapeutic potential

Abstract

Abstract Tuberculosis remains the leading cause of death from a single infectious pathogen, driven by prolonged treatment regimens and escalating drug resistance. Antimicrobial peptides represent a promising alternative therapeutic class with diverse mechanisms and limited resistance emergence. This review distinguishes anti-mycobacterial from anti- Mycobacterium tuberculosis peptides and systematically analyses 22 candidates curated in the APD6 alongside additional literature reports. We evaluate their structural and physicochemical determinants of activity, mechanistic evidence in vitro and in vivo, and synergy with conventional agents. Finally, we discuss rational design strategies, machine learning-guided optimisation, and translational barriers that must be overcome to realise peptide-based tuberculosis therapeutics.