Antimicrobial peptides (AMPs), evolutionarily conserved components of the immune system, have attracted considerable attention as promising therapeutic candidates. Derived from diverse organisms, AMPs represent a heterogeneous class of molecules, typically cationic, which facilitates their initial electrostatic interaction with anionic microbial membranes. Unlike conventional single-target antibiotics, AMPs utilize rapid, multi-target mechanisms, primarily physical membrane disruption, which results in a significantly lower incidence of resistance emergence. Their broad-spectrum antimicrobial activity, capacity to modulate host immunity, and unique mechanisms of action make them inherently less susceptible to resistance compared with traditional antibiotics. Despite these advantages, the clinical translation of natural AMPs remains limited by several challenges, including poor in vivo stability, and potential cytotoxicity. Bioengineering technology offers innovative solutions to these limitations of AMPs. Two techniques have demonstrated promise: (i) a chimeric recombinant of AMPs with stable scaffold, such as human serum albumin and antibody Fc domain and (ii) chemical modification approaches, such as lipidation. This review provides a comprehensive overview of AMPs, highlighting their origins, structures, and mechanisms of antimicrobial activity, followed by recent advances in bioengineering platforms designed to overcome their therapeutic limitations. By integrating natural AMPs with bioengineering and nanotechnologies, AMPs may be developed into next-generation antibiotics.

Many anti-microbial peptides (AMPs) and pro-apoptotic peptides are considered as novel anti-microbial agents, distinguished by their different characteristics. Nevertheless, AMPs exhibit certain limitations, including poor stability and potential toxicity, which hinder their suitability for applications in pharmaceutics and medical devices. In this study, we used recombinant mussel adhesive protein (MAP) as a robust scaffold to overcome these limitations associated with AMPs. Mussel adhesive protein fused with functional peptides (MAP-FPs) was used to evaluate anti-microbial activities, minimal inhibitory concentration (MIC), and time-kill kinetics (TKK) assays against six of bacteria strains. MAP and MAP-FPs were proved to have an anti-microbial effect with MIC of 4 or 8 µM against only Gram-negative bacteria strains. All tested MAP-FPs killed four different Gram-negative bacteria strains within 180 min. Especially, MAP-FP-2 and -5 killed three Gram-negative bacteria strain, including E. coli, S. typhimurium, and K. pneumoniae, within 10 min. A cytotoxicity study using Vero and HEK293T cells indicated the safety of MAP and MAP-FP-2 and -3. Thermal stability of MAP-FP-2 was also validated by HPLC analysis at an accelerated condition for 4 weeks. This study identified that MAP-FPs have novel anti-microbial activity, inhibiting the growth and rapidly killing Gram-negative bacteria strains with high thermal stability and safety.