Antimicrobial Peptides: Vestiges of Past or Modern Therapeutics?

Abstract

The ubiquitous occurrence of Antimicrobial Peptides (AMPs) in all domains of life emphasizes their crucial role as ancient mediators of host defense. Despite their antiquity and prolonged history of exposure to pathogens, endogenous AMPs continue to serve as effective antibiotics. An "evolutionary arms race" between host and pathogen resulted in structural diversity of AMPs, leading these molecules to retain activity against a wide range of pathogens, including antibiotic-resistant microbes. As the menace of antibiotic resistance continues to render most antibiotics ineffective against pathogens, the search for novel drug candidates has taken the center stage. The ability of AMPs to combat antibiotic-resistant microbes gave rise to a remarkable surge of interest in AMPs as potential therapeutics. Apart from being effective antimicrobials, AMPs have also found application as probes suitable for in-situ diagnosis of infection. Here, we review the evolutionary history of AMPs, their structural diversity, and mechanism of interaction with microbial membranes. We also summarize the role of AMPs as modern pharmaceuticals and challenges to this development.

Expanding a peptide-covalent probe hybrid for PET imaging of S. aureus driven focal infections

“…AMPs are reported to destroy bacterial cells by permeabilizing the membrane, followed by depolarization (Mitra et al 2020 ; Bhatt Mitra et al 2020 ). To explore if UBI-APBA utilized this strategy to adversely affect the survival of S. aureus , depolarization and permeabilization of S. aureus membrane was studied by flow cytometry.…”

“…4 ). Several AMPs that demonstrate strong antibacterial activity encounter challenges due to their toxicity to human red blood cells (RBCs), leading to a diminished therapeutic potential (Mitra et al 2020 ). The low therapeutic index or TI (TI = Haemolytic dose /MIC causing 50% lysis or HD 50 ) of such AMPs make their clinical translation extremely difficult.…”

Protective Effects of Bacteriocin-Producing Lactiplantibacillus plantarum on Intestinal Barrier of Mice

“…When the effects of bacteriocin-producing L. plantarum on the intestinal immunological barrier were explored, the results revealed that the two strains promoted the release of IgA and IgG in the serum and intestine to varying degrees, which suggested that bacteriocin-producing strains could strengthen the intestinal immune function, but there existed differences when different strains acted on immunoglobulins in distinct tissues of mice. Antimicrobial peptides are crucial participants in host natural defense and play a significant part in innate immunity [ 25 ]. The antimicrobial peptide RegIIIγ, produced by Paneth cells, can protect mice from pathogens infection, regulate intestinal microecological balance, and maintain immune homeostasis [ 26 ].…”

The design and evaluation of the antimicrobial activity of a novel conjugated penta-ultrashort antimicrobial peptide in combination with conventional antibiotics against sensitive and resistant strains of S. aureus and E. coli.

“…AMPs represent an attractive class of molecules for antimicrobial drug development due to their intrinsic wide-spectrum antimicrobial activity. Several efforts have been undertaken to move AMPs into the clinic as effective therapeutics with little success due to the toxicity issues associated with this class of molecules and their high manufacturing costs( 21 ). To overcome these obstacles, recent efforts focused on alleviating these issues by designing USAMPs that can be attractive candidates for drug development as they would allow large-scale production with economic feasibility and provides a significant reduction in manufacturing costs due to simplicity in their structure and short amino acid sequence.…”