Antimicrobial Peptides—Mechanisms of Action, Antimicrobial Effects and Clinical Applications

Abstract

The growing emergence of antimicrobial resistance represents a global problem that not only influences healthcare systems but also has grave implications for political and economic processes. As the discovery of novel antimicrobial agents is lagging, one of the solutions is innovative therapeutic options that would expand our armamentarium against this hazard. Compounds of interest in many such studies are antimicrobial peptides (AMPs), which actually represent the host’s first line of defense against pathogens and are involved in innate immunity. They have a broad range of antimicrobial activity against Gram-negative and Gram-positive bacteria, fungi, and viruses, with specific mechanisms of action utilized by different AMPs. Coupled with a lower propensity for resistance development, it is becoming clear that AMPs can be seen as emerging and very promising candidates for more pervasive usage in the treatment of infectious diseases. However, their use in quotidian clinical practice is not without challenges. In this review, we aimed to summarize state-of-the-art evidence on the structure and mechanisms of action of AMPs, as well as to provide detailed information on their antimicrobial activity. We also aimed to present contemporary evidence of clinical trials and application of AMPs and highlight their use beyond infectious diseases and potential challenges that may arise with their increasing availability.

Cell-Penetrating Antimicrobial Peptides with Anti-Infective Activity against Intracellular Pathogens

“…Native AMPs are widely found in organisms’ cells, tissues, and biological fluids and are essentially involved in the innate defense of the host against invading pathogens. They kill microbes by diverse but convergent mechanisms of cell disruption that essentially compromise the integrity of the cytoplasmic membranes [ 25 , 26 ], which serve as a portal for the synergic action of chemotherapeutics [ 27 ]. A handful of exciting reviews about the structures, activities, and mechanisms of action of CPPs and AMPs [ 28 , 29 , 30 ] are available.…”

Synthesis of temporin L hydroxamate-based peptides and evaluation of their coordination properties with iron(iii )

“…20 This strategy is known as the Trojan horse approach. 21 Similarly, antimicrobial peptides (AMPs), which are widely studied and considered a promising alternative to traditional antibiotics for their mode of action, [22][23][24][25][26][27][28] may be linked to siderophoreiron chelators to reduce the iron availability for bacterial growth and enhance their efficacy (Fig. 1).…”

Peptidomic analysis of the host-defense peptides in skin secretions of the Amazon River frog Lithobates palmipes (Ranidae)

“…Frog skin HDPs have excited interest as a source of potentially valuable therapeutic agents. Although their growth-inhibitory activity against bacteria and fungi, including antibiotic-resistant strains, has been the most extensively studied (Xu and Lai, 2015;Talapko et al, 2022), the HDPs are multifunctional and other potentially important clinically relevant properties include immunomodulatory, wound healing antioxidant antiviral, anticancer, and antidiabetic actions [reviewed in (Conlon et al, 2019;Haney et al, 2019)]. However, it must be pointed out the initial promise of using the repository of biologically active peptides present in the skins of frogs as a source of new drugs has yet to be fulfilled as no compound derived from amphibian HDPs is currently in clinical practice.…”