Aspirin-Conjugated Cholic Acid Derivative Combats Polymicrobial Infections and Inflammation.

Treating wound infections caused by Gram-positive and Gram-negative bacteria, along with associated inflammation, remains challenging due to the limited therapeutic efficacy of conventional antibiotics. Leveraging the unique properties of cholic acid derivatives, such as their cationic nature, hydrophobicity, and structural adaptability, a novel aspirin-derived facile amphiphile based on cholic acid (amphiphile 1) is designed and synthesized. The investigations reveal that the amphiphile 1 functions as a bacterial membrane disruptor through interacting with key components such as lipoteichoic acid and lipopolysaccharide of bacterial membranes. It is observed that amphiphile 1 can degrade both monomicrobial and polymicrobial preformed biofilms originating from Gram-positive and Gram-negative bacteria. Animal studies demonstrate that hydrogel-based delivery of amphiphile 1 effectively mitigates bacterial infections and resolves bacterial-associated inflammation. Collectively, these findings underscore that amphiphile 1 is a putative therapeutic agent for addressing the challenges of polymicrobial infections.