Chitosan-Based Peptidopolysaccharides as Cationic Antimicrobial Agents and Antibacterial Coatings

Abstract

The rapid spread of multidrug-resistant bacteria has called for effective antimicrobial agents which work on a more direct mechanism of killing. Cationic peptidopolysaccharides are developed in the present work to mimic the peptidoglycan structure of bacteria and to enhance the membrane-compromising bactericidal efficacy. Antimicrobial CysHHC10 peptide was grafted to the C-2 (amino) or C-6 (hydroxyl) position of chitosan backbone via thiol-maleimide "click" conjugation, utilizing the maleimidohexanoic linkers. The peptidopolysaccharide with primary amino backbone intact (CSOHHC) exhibited higher bactericidal activity toward Gram-positive and Gram-negative bacteria, in comparison to that with amino backbone grafted with the peptide (CSNHHC). Both peptidopolysaccharides also exhibited lower hemolytic activity and cytotoxicity than free CysHHC10 peptide due to the moderation effect contributed by the chitosan backbone. For targeting the Gram-positive bacteria in particular, the CSOHHC expressed 4- and 2-fold increases in hemo- and cytoselectivity, respectively, as compared to the CysHHC10 peptide. In an extended application, peptidopolysaccharide antibacterial coatings were formed via layer-by-layer assembly with tannic acid. The peptidopolysaccharide coatings readily killed the adhered bacteria upon contact while being cytocompatible by maintaining more than 60% viability for the adhered fibroblasts. Therefore, the peptidoglycan-mimetic peptidopolysaccharides are potential candidates for anti-infective drugs in biomedical applications.

Cationic chitosan derivatives as potential antifungals: A review of structural optimization and applications

“…Generally, cationic chitosan derivatives not only has good water solubility and antifungal activity, but also maintains the advantages of good biocompatibility and biodegradability of chitosan. Moreover, it can also be processed by copolymerization, crosslinking, blending, forming complex with metal ions, and so on, so as to obtain materials, such as membranes, gels, coating, scaffolds, for different uses (Hassan, 2018;Mohamed & Abd El-Ghany, 2018;Mohamed, Elella, & Sabaa, 2015;Pranantyo et al, 2018;Tabriz et al, 2019). Among the diverse applications of cationic chitosan derivatives to inhibit fungi, one of the most noticeable may be its disinfection control in clinics, hospitals and some medical environments.…”

“…To address this problem, there is a growing interest imparting AMPs with the versatility of polysaccharides to reduce the toxicity (Barbosa, Vale, Costa, Martins, & Gomes, 2017;. In particular, chitosan is thought to be an ideal material to use for conjugation with AMPs due to its high biocompatibility (Pranantyo, Xu, Kang, & Chan-Park, 2018). Therefore, some recent studies have attempted to obtain new conjugates by coupling chitosan with peptides/amino acids to study whether they have synergistic effects (Kim et al, 2016;Patrulea et al, 2016).…”

“…It was found that C6 substituted chitosan peptide showed higher activity of than that of C2 substituted. And it was inferred that the existence of C2 free amino group may have a great influence on the activity (Pranantyo et al, 2018). Before discussing and summarizing the antifungal activity of chitosan peptide (amino acid) conjugates, it should be pointed out that the above strategies are mainly aimed at antibacterial chitosan peptide (amino acid) conjugates.…”

Supramolecular Antibacterial Materials for Combatting Antibiotic Resistance

“…Following the report by Hou et al, a chitosan‐based peptidopolysaccharide was developed by Pranantyo et al for enhancing antibacterial treatment . In this system, a novel peptidopolysaccharide was designed to mimic the bacterial peptidoglycan structure and to increase the membrane‐compromising antibacterial efficacy.…”

Substrate‐Independent Coating with Persistent and Stable Antifouling and Antibacterial Activities to Reduce Bacterial Infection for Various Implants

“…(PEG) conjugated antimicrobial peptides and cationic polymers on material surface, which performed effective prevention of biofilm formation, moderate toxicity, low drug-resistance, and high killing potency toward a broad spectrum of bacteria. [5,[16][17][18][19] However, the fabrication of these coatings is normally based on the surface chemistry methods, which involve either multiple steps, high costs of the active materials, rigorous water/ oxygen-free reaction conditions or relative catalysts, resulting in potential biohazards, [20][21][22][23] which are difficult and expensive to produce in practice. Second, these protocols all required specific substrates with certain functional groups on the surface, which further limited their applications.…”