An overview of antimicrobial peptides and the latest advances in their development

Abstract

The recent dramatic increase in the incidence of antimicrobial resistance has been recognized by organizations such as the United Nations and World Health Organization as well as the governments of the USA and several European countries. A relatively new weapon in the fight against severe infections caused by multi-drug resistant bacteria is antimicrobial peptides (AMPs). These include colistin, currently regarded as the last line of antimicrobial therapy against multi-drug resistant microorganisms. Areas covered: Here, the authors provide an overview of the current research on AMPs. The focus is AMPs currently being developed for the treatment of recalcitrant bacterial infections, the synergies of AMPs and antibiotics, and the activity of AMPs against biofilm. This review also includes a brief introduction into the use of AMPs in infections caused by Mycobacterium, fungi, and parasites. Expert opinion: In research into new antimicrobials, AMPs are gaining increasing attention. While many are natural and are produced by a wide variety of organisms, others are being newly designed and chemically synthesized in the laboratory to achieve novel antimicrobial agents. The same strategy to fight infections in nature is thus being effectively exploited to safeguard human and animal health.

Development and evaluation of cationic amphiphilic antimicrobial 2,5‐diketopiperazines

“…Antimicrobial peptides (AMPs) constitute an important part of the innate defense toward pathogens and have been heralded as a new source of antifungal drugs . Several studies have been devoted to establishing the antifungal activities of natural AMPs, and the area was recently reviewed by van der Weerden and co‐workers .…”

“…One such synthetic example is the synthetic kaxin family developed by Burrows et al These peptides displayed superior antifungal properties compared with magainin II and cecropin P1 but were 1 order of magnitude less potent than fluconazole . Another noteworthy promising synthetic antifungal peptidic compound is the cyclic arginine heptamer NP213 (Novexatin, NovaBiotics), which has undergone phase II clinical trials for mild‐to‐moderate onychomycosis . The recently reported library of small synthetic peptide mimics by Diamond and co‐workers was also shown to contain selected promising compounds active against oral Candida strains and superior to nystatin in a mouse model.…”

Drug delivery systems designed to overcome antimicrobial resistance

“…With regard to the Trojan horse strategy, we will focus on the conjugation of ATBs with AMPs, the latter serving as delivery vehicules for the former. Other potential applications of AMPs in anti‐infectious treatment have already been studied in previous reviews …”

Harnessing snake venom phospholipases A2 to novel approaches for overcoming antibiotic resistance

“…Even when structure–activity issues are conveniently dealt with, one needs to address the greatest challenge of all in developing a peptide‐based drug: the generally poor absorption, distribution, metabolism, and excretion (ADME) properties of natural peptides, the vast majority of which display an oral bioavailability below 1% (Di, ). Setting aside peptide encapsulation strategies, which lay beyond scope of this review, a few classical strategies to tackle this situation include (a) N‐terminal acylation and C‐terminal amidation, to avoid proteolytic degradation by amino and carboxypeptidases, respectively; (b) identification of sites amenable to undergo proteolysis by endopeptidases, in order to perform suitable backbone modifications, like replacement of the labile amide bond by a bioisostere, or of l ‐amino acids by their N‐methylated and/or D‐enantiomer counterparts, or by β‐amino acid analogues; (c) increase stability and/or lock conformation upon cyclization; (d) coupling to a small serum protein‐ligand molecule to increase blood circulation time, or (e) production of peptidomimetics, including peptoids, peptaibols, azapeptides and other mimetics, though this approach is the least attractive, as it usually joins additional synthetic effort with relevant drop in activity (Di, ; Henninot et al, ; Molchanova, Hansen, & Franzyk, ; Qvit, Rubin, Urban, Mochly‐Rosen, & Gross, ; Raza et al, ; Sierra, Fusté, Rabanal, Vinuesa, & Viñas, ).…”