Main-Chain Cationic Bile Acid Polymers Mimicking Facially Amphiphilic Antimicrobial Peptides

Abstract

Antibiotic-resistant bacterial infections have led to an increased demand for antibacterial agents that do not contribute to antimicrobial resistance. Antimicrobial peptides (AMPs) with the facially amphiphilic structures have demonstrated remarkable effectiveness, including the ability to suppress antibiotic resistance during bacterial treatment. Herein, inspired by the facially amphiphilic structure of AMPs, the facially amphiphilic skeletons of bile acids (BAs) are utilized as building blocks to create a main-chain cationic bile acid polymer (MCBAP) with macromolecular facial amphiphilicity via polycondensation and a subsequent quaternization. The optimal MCBAP displays an effective activity against Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative Escherichia coli, fast killing efficacy, superior bactericidal stability in vitro, and potent anti-infectious performance in vivo using the MRSA-infected wound model. MCBAP shows the low possibility to develop drug-resistant bacteria after repeated exposure, which may ascribe to the macromolecular facial amphiphilicity promoting bacterial membrane disruption and the generation of reactive oxygen species. The easy synthesis and low cost of MCBAP, the superior antimicrobial performance, and the therapeutic potential in treating MRSA infection altogether demonstrate that BAs are a promising group of building blocks to mimic the facially amphiphilic structure of AMPs in treating MRSA infection and alleviating antibiotic resistance.

Imidazolium‐Based Main‐Chain Copolymers With Alternating Sequences for Broad‐Spectrum Bactericidal Activity and Eradication of Bacterial Biofilms

“…Their systematic exploration demonstrated that MCBAP with amphiphilic structure displayed an effective activity against Gram-positive methicillin-resistant Staphylococcus aureus and Gram-negative Escherichia coli, fast killing efficacy, superior bactericidal stability in vitro, and potent anti-infection. [38] Upon adsorption onto the bacterial membrane surface, antibacterial polymers initiate interactions with microorganisms through their hydrophobic segments, leading to the disruption of membrane integrity. The nature of these hydrophobic segments, including their category, length, and position, has been reported to exert a significant impact on the bactericidal efficiency.…”

“…Their systematic exploration demonstrated that MCBAP with amphiphilic structure displayed an effective activity against Gram‐positive methicillin‐resistant Staphylococcus aureus and Gram‐negative Escherichia coli , fast killing efficacy, superior bactericidal stability in vitro, and potent anti‐infection. [ 38 ]…”