Antimicrobial Peptides: From Design to Clinical Application

Abstract

Infection of multidrug-resistant (MDR) bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli, brings public health issues and causes economic burden. Pathogenic bacteria develop several methods to resist antibiotic killing or inhibition, such as mutation of antibiotic function sites, activation of drug efflux pumps, and enzyme-mediated drug degradation. Antibiotic resistance components can be transferred between bacteria by mobile genetic elements including plasmids, transposons, and integrons, as well as bacteriophages. The development of antibiotic resistance limits the treatment options for bacterial infection, especially for MDR bacteria. Therefore, novel or alternative antibacterial agents are urgently needed. Antimicrobial peptides (AMPs) display multiple killing mechanisms against bacterial infections, including directly bactericidal activity and immunomodulatory function, as potential alternatives to antibiotics. In this review, the development of antibiotic resistance, the killing mechanisms of AMPs, and especially, the design, optimization, and delivery of AMPs are reviewed. Strategies such as structural change, amino acid substitution, conjugation with cell-penetration peptide, terminal acetylation and amidation, and encapsulation with nanoparticles will improve the antimicrobial efficacy, reduce toxicity, and accomplish local delivery of AMPs. In addition, clinical trials in AMP studies or applications of AMPs within the last five years were summarized. Overall, AMPs display diverse mechanisms of action against infection of pathogenic bacteria, and future research studies and clinical investigations will accelerate AMP application.

Newly Emerged Antiviral Strategies for SARS-CoV-2: From Deciphering Viral Protein Structural Function to the Development of Vaccines, Antibodies, and Small Molecules

“…Small peptides can be designed and used as inhibitors to prevent the infection of viruses and other infectious pathogens [ 105 , 106 ]. For example, the N-terminal helix of the hACE2 contains the amino acids that mediated the interaction of hACE2 with the virus.…”

Structure–Activity Relationship of New Chimeric Analogs of Mastoparan from the Wasp Venom Paravespula lewisii

“…In recent years, many research groups have focused their attention on antimicrobial peptides (AMPs) as a novel class of antibiotics [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. These peptides, as an important element of the body’s natural immunity against microorganisms, are widespread in nature and exhibit a broad spectrum of antimicrobial activity and low susceptibility to the development of drug resistance [ 1 , 2 , 3 ].…”

“…In recent years, many research groups have focused their attention on antimicrobial peptides (AMPs) as a novel class of antibiotics [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. These peptides, as an important element of the body’s natural immunity against microorganisms, are widespread in nature and exhibit a broad spectrum of antimicrobial activity and low susceptibility to the development of drug resistance [ 1 , 2 , 3 ]. Generally, AMPs are relatively short cationic amphipathic peptides consisting of 5–40 amino acids in their sequence, which carry a net positive charge (usually 2–10 charged residues) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ].…”

“…These peptides, as an important element of the body’s natural immunity against microorganisms, are widespread in nature and exhibit a broad spectrum of antimicrobial activity and low susceptibility to the development of drug resistance [ 1 , 2 , 3 ]. Generally, AMPs are relatively short cationic amphipathic peptides consisting of 5–40 amino acids in their sequence, which carry a net positive charge (usually 2–10 charged residues) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Their amino acid sequences are composed of hydrophilic and hydrophobic residues, whereby they are soluble in both the aqueous and lipid phases [ 5 , 7 ].…”

“…AMPs kill pathogens through lethal cell permeabilization or inhibition of intracellular targets (e.g., inhibition of protein or nucleic acid biosynthesis, protease activity) [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. The antimicrobial activity of AMPs seems most likely to be a consequence of their interaction with the bacterial membrane, including translocation across the membrane, association into clusters, or the formation of pores on the membrane (including the carpet model, barrel stave model, toroidal pore model or “detergent”-like model) [ 1 , 2 , 5 , 6 , 7 , 8 , 9 ].…”