Cholic Acid-Derived Gemini Amphiphile Can Eradicate Interkingdom Polymicrobial Biofilms and Wound Infections.

Biofilm infections are mainly caused by Gram-positive bacteria (GPB) like , Gram-negative bacteria (GNB) like , and fungi like . These infections are responsible for antimicrobial tolerance, and commensal interactions of these microbes pose a severe threat to chronic infections. Treatment therapies against biofilm infections are limited to eradicating only 20-30% of infections. Here, we present the synthesis of a series of bile acid-derived molecules using lithocholic acid, deoxycholic acid, and cholic acid where two bile acid molecules are tethered through 3'-hydroxyl or 24'-carboxyl terminals with varying spacer length (trimethylene, pentamethylene, octamethylene, and dodecamethylene). Our structure-activity relationship investigations revealed that , a cholic acid-derived gemini amphiphile having trimethylene spacer tethered through the C24 position, is a broad-spectrum antimicrobial agent. Biochemical studies witnessed that interacts with negatively charged lipoteichoic acid, lipopolysaccharide, and phosphatidylcholine moieties of GPB, GNB, and fungi and disrupts the microbial cell membranes. We further demonstrated that can eradicate polymicrobial biofilms and wound infections and prevent bacteria and fungi from developing drug resistance. Therefore, our findings revealed the potential of as a versatile antimicrobial agent capable of effectively targeting polymicrobial biofilms and wound infections, suggesting that it is a promising antimicrobial agent for future applications.