Antimicrobial Peptides and Macromolecules for Combating Microbial Infections: From Agents to Interfaces

Abstract

Bacterial resistance caused by the overuse of antibiotics and the shelter of biofilms has evolved into a global health crisis, which drives researchers to continuously explore antimicrobial molecules and strategies to fight against drug-resistant bacteria and biofilm-associated infections. Cationic antimicrobial peptides (AMPs) are considered to be a category of potential alternative for antibiotics owing to their excellent bactericidal potency and lesser likelihood of inducing drug resistance through their distinctive antimicrobial mechanisms. In this review, the hitherto reported plentiful action modes of AMPs are systematically classified into 15 types and three categories (membrane destructive, nondestructive membrane disturbance, and intracellular targeting mechanisms). Besides natural AMPs, cationic polypeptides, synthetic polymers, and biopolymers enable to achieve tunable antimicrobial properties by optimizing their structures. Subsequently, the applications of these cationic antimicrobial agents at the biointerface as contact-active surface coatings and multifunctional wound dressings are also emphasized here. At last, we provide our perspectives on the development of clinically significant cationic antimicrobials and related challenges in the translation of these materials.

Surface modification of SiO2 nanoparticles for bacterial decontaminations of blood products

“…Some research has been done on surface modification with antimicrobial peptides (AMP) as amphiphilic cationic structures, which can bind to anionic bacterial membranes by electrostatic attraction leading to bacterial death [51]. The mechanism of action of AMPs remains complex and poorly studied, and the main problem associated with the clinical use of AMPs is their possible cytotoxicity [52].…”

Antimicrobial mechanisms of biomaterials: from macro to nano

“…Direct physical contact-mediated membrane disruption through pore-forming or non-pore-forming pathways, and oxidative stress causing membrane damage and subsequent cellular oxidation of biomolecules have been proposed as mechanisms of antimicrobial activity. 23 The key focus of this review is to provide comprehensive and up-to-date knowledge about the current understanding on how biomaterials ranging from macroscale to nanoscale exert their antibacterial and antiviral actions, and specifically present the readers with an organized overview of their different modes of action. However, discussions, comparisons and evaluations of antibacterial and antiviral efficiencies of different biomaterials in terms of their therapeutic dosage are beyond the scope of this review.…”

“…Direct physical contact-mediated membrane disruption through pore-forming or non-pore-forming pathways, and oxidative stress causing membrane damage and subsequent cellular oxidation of biomolecules have been proposed as mechanisms of antimicrobial activity. 23…”

A degradable, broad-spectrum and resistance-resistant antimicrobial oligoguanidine as a disinfecting and therapeutic agent in aquaculture

“…They may function via different mechanisms, such as membrane destruction, non-destructive membrane disturbance, and intracellular targeting mechanisms. 27 Among these polymers, the membrane-targeting, resistance-resistant synthetic antimicrobial peptides, antimicrobial peptidomimetics and antimicrobial polymers attract the most attention. [28][29][30][31][32][33][34][35][36][37][38][39] The lipophilic-cationic groups on these agents can bind to the negatively charged phospholipids or lipopolysaccharides of the bacterial membrane through electrostatic and hydrophobic interactions, severely disrupting the membrane and leading to bacterial cell death.…”

“…However, the membrane disrupting nature of these novel antibacterial agents also brings concerns on eukaryotic cytotoxicity, and a tremendous amount of work has been reported in finding solutions for the cytotoxicity issues, including but not limited to structural modification of antimicrobial peptides and their mimics, [44][45][46] spatial conformation, 47,48 trigger-responsive designs, [49][50][51] and introduction of a secondary mechanism of action. [52][53][54][55][56][57] Inspired by the known non-membrane targeting working mechanism of these antimicrobial polymers, 27 the development of agents with dual mechanisms of action that target both the membrane and an intracellular target have been shown to significantly improve the performance of such antimicrobials, making them strongly bactericidal at low concentrations with fast-killing kinetics. 54,55,58 Considering that low working concentrations and fast killing kinetics are highly valued in aquaculture maintenance, we wondered if a dualmechanistic antimicrobial oligomer suitable as a disinfecting and therapeutic agent in aquaculture could be obtained from screening using chemistry analogous to our previously reported systems.…”