Perspectives for clinical use of engineered human host defense antimicrobial peptides

Abstract

Infectious diseases caused by bacteria, viruses or fungi are among the leading causes of death worldwide. The emergence of drug-resistance mechanisms, especially among bacteria, threatens the efficacy of all current antimicrobial agents, some of them already ineffective. As a result, there is an urgent need for new antimicrobial drugs. Host defense antimicrobial peptides (HDPs) are natural occurring and well-conserved peptides of innate immunity, broadly active against Gram-negative and Gram-positive bacteria, viruses and fungi. They also are able to exert immunomodulatory and adjuvant functions by acting as chemotactic for immune cells, and inducing cytokines and chemokines secretion. Moreover, they show low propensity to elicit microbial adaptation, probably because of their non-specific mechanism of action, and are able to neutralize exotoxins and endotoxins. HDPs have the potential to be a great source of novel antimicrobial agents. The goal of this review is to provide an overview of the advances made in the development of human defensins as well as the cathelicidin LL-37 and their derivatives as antimicrobial agents against bacteria, viruses and fungi for clinical use.

Alzheimer’s Disease-Associated β-Amyloid Is Rapidly Seeded by Herpesviridae to Protect against Brain Infection

“…Next, we investigated possible carbohydrate moieties on herpesviridae that Aβ may target. Classical heparin-binding AMPs target viral glycoproteins, including LL-37 (Pachon-Ibanez et al, 2017) and θ and α -defensins (Hazrati et al, 2006). Immobilized HSV1 was pre-incubated with antibodies to herpesviridae glycoproteins B (gB), C (gC), D (gD), E (gE), H (gH), or G (gG) prior to incubation with conditioned CHO-CAB media.…”

Research on the effect and mechanism of antimicrobial peptides HPRP‐A1/A2 work against Toxoplasma gondii infection

“…They are important in the host's innate immune defence system. 16,38 Previous studies have reported that AMPs possess strong antimicrobial activity against gram-negative and gram-positive bacteria as well as some main pathogenic fungi. 21,39,40 In view of this, some researchers have tried to test their killing efficacy of AMPs against parasites.…”

Antimicrobial peptides activity in the skin

“…Moreover, unique peptides phenol‐soluble modulins (PSM γ and PSM δ) produced by S. epidermidis can selectively inhibit the skin pathogens and help to maintain the normal skin microbiome . This multi‐directional mechanism of action of AMPs indicates that these peptides not only have low propensity to elicit microbial adaptation but also are able to neutralize exotoxins and endotoxins produced by microbes …”

“…37 This multi-directional mechanism of action of AMPs indicates that these peptides not only have low propensity to elicit microbial adaptation but also are able to neutralize exotoxins and endotoxins produced by microbes. 38,39…”