Synthetic antibiofilm peptides

Abstract

Bacteria predominantly exist as multicellular aggregates known as biofilms that are associated with at least two thirds of all infections and exhibit increased adaptive resistance to conventional antibiotic therapies. Therefore, biofilms are major contributors to the global health problem of antibiotic resistance, and novel approaches to counter them are urgently needed. Small molecules of the innate immune system called host defense peptides (HDPs) have emerged as promising templates for the design of potent, broad-spectrum antibiofilm agents. Here, we review recent developments in the new field of synthetic antibiofilm peptides, including mechanistic insights, synergistic interactions with available antibiotics, and their potential as novel antimicrobials against persistent infections caused by biofilms. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert.

Keywords: Antibiotic resistance; Biofilms; Biomaterials; Persistent infections; Synergy; Synthetic peptides.

Figure 1. Potential biotechnological uses of HDPs and their synthetic analogues

HDPs and their derivatives can act both by direct killing of biofilms (alone or in combination with conventional antibiotics), being able to cause damage to the membrane of the targets cells, as well as by interfering with the homeostasis of the intracellular environment; and by immunomodulation, where the peptides posses the ability to recruit and activate cells from the immune system, facilitating bacterial clearance and increasing wound healing.

Figure 2. Medical device coating strategy, layer-by-layer assembly and nanoparticle engineering to counteract biofilm formation

(A) Representation of bacterial biofilm formation within a medical device before (top middle) and after coating with antibiofilm peptides (top right). The polymer illustrated below is a fusion of polydimethylsiloxane (PDMS), allyl glycidyl ether (AGE) and maleimide – polyethylene glycol (PEG) – amine whose maleimide group is used for a sulfhydryl coupling with the antibiofilm peptide containing a cysteine residue at the N-terminus. (B) Layer-by-layer construction consisting of the poly 2 (β-amino ester) and alginic acid (polyanion) in which HPDs are incorporated and subsequently released. (C) Engineered poly (lactide-co-glycolide) (PGLA) nanoparticles (NPs) coated with hydrophilic polymers (chitosan; PVA), which are able to optimize the efficiency of entrapment and modulate surface properties. HDPs are encapsulated within NPs, and are then released near and/or inside pre-formed biofilms.