Recent advances in the development of antimicrobial peptides against ESKAPE pathogens

Abstract

Multi-drug resistant ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are a global health threat. The severity of the problem lies in its impact on mortality, therapeutic limitations, the threat to public health, and the costs associated with managing infections caused by these resistant strains. Effectively addressing this challenge requires innovative approaches to research, the development of new antimicrobials, and more responsible antibiotic use practices globally. Antimicrobial peptides (AMPs) are a part of the innate immune system of all higher organisms. They are short, cationic and amphipathic molecules with broad-spectrum activity. AMPs interact with the negatively charged bacterial membrane. In recent years, AMPs have attracted considerable interest as potential antibiotics. However, AMPs have low bioavailability and short half-lives, which may be circumvented by chemical modification. This review presents recent in vitro and in silico strategies for the modification of AMPs to improve their stability and application in preclinical experiments.

Fig. 1

Models of generated E. coli liposomes represented as outer membrane (OM) with (C) and without cholesterol (A), Inner membrane (IM) with (D) or without cholesterol (B). Interaction between liposomes with cholesterol and the JB95 peptide in OM (E) and in IM (F). Lipids are represented in sticks where lipid A is in white, 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylethanolamine in green, 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylglycerol in cyan and cardiolipin in grid. Figure reprinted and edited from Franco-Gonzalez et al. [98] Open Access from Scientific Reports by Nature Portfolio 2022. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)