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.
Despite the excellent antimicrobial activity, the high toxicity and low selectivity of cationic antimicrobial peptides (AMPs) and their synthetic analogues impede their biomedical applications. In this study, we report a series of cationic peptidopolysaccharides synthesized by thiol−ene click chemistry of grafting antimicrobial polypeptides, methacrylate-ended poly(lysine-random-phenylalanine) (Me-K n F m ), onto a thiolated polysaccharide (dextran, Dex) backbone. Their copolymers (Dex-g-K n F m ) exhibit potent broad-spectrum antibacterial and antifungal activity against Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli), Gram-positive bacteria [methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis], and fungi (Candida albicans) with minimal inhibitory concentrations in the range of 31.25−500 μg•mL −1 . More importantly, Dex-g-K n F m copolymers did not induce drug resistance of MRSA up to 17 passages. In addition, these copolymers have an improved hemocompatibility and exhibit good in vitro biocompatibility with murine myoblast (C2C12) cells. Among the synthesized peptidopolysaccharides, Dex L -g-K 12.5 F 12.5 -50%, as the optimal agent, displayed a selectivity more than 200 times the maximum value of polypeptide molecules. Furthermore, a strong in vivo antimicrobial efficacy with a log reduction above 3 in a mouse bacterial sepsis model has been obtained. These excellent biological properties present a promising prospect for Dexg-K n F m in biomedical applications.
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