Hybrid and conjugated antimicrobial peptides: new tactics to counter bacterial resistance

The phenomenon of bacterial resistance has emerged as a significant challenge to global public health. Due to the increasing prevalence of antibiotic resistance, there has been interest in developing antimicrobial peptides (AMPs) as alternative antimicrobial therapies. However, AMPs resistance is not uncommon; it is simply subject to complex ecological and physiological limitations. While AMPs demonstrate potent antimicrobial activity in experimental and preclinical studies, their clinical efficacy remains limited. This review mainly summarizes the two methods of peptide hybridization and conjugation to combat drug-resistant bacteria. Hybridization has given AMPs new vitality, which overall enhance their antimicrobial spectrum, reduce toxicity, and enhance the bactericidal effect on drug-resistant strains. We also reviewed the conjugation of AMPs with various active molecules, such as antibiotics, antibodies, fatty acids, photosensitizers, phosphodiester oligomers, and nanoparticles. This review provides ideas for the design of hybrid peptides and coupled peptides in the future, and these AMPs have been shown to have an effect on drug-resistant strains after hybridization or coupling, thereby making the originally ineffective AMPs regain sensitivity. The transformation of natural AMPs has been effective in the laboratory to some extent, and give it clinical exploration value. Their clinical performance still falls short of that of conventional antibiotics due to challenges related to pharmacokinetics, safety, and reduced activity under clinically relevant conditions. To break through the bottleneck of clinical transformation of AMPs, it is necessary to continue to deepen multi-dimensional research on their physicochemical properties and make good use of artificial intelligence technology for intelligent design and high-throughput verification of hybrid peptides or conjugated peptides.