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

Biofilm infections are mainly caused by Gram-positive bacteria (GPB) like Staphylococcus aureus, Gram-negative bacteria (GNB) like Pseudomonas aeruginosa, and fungi like Candida albicans. 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 G21, a cholic acid-derived gemini amphiphile having trimethylene spacer tethered through the C24 position, is a broad-spectrum antimicrobial agent. Biochemical studies witnessed that G21 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 G21 can eradicate polymicrobial biofilms and wound infections and prevent bacteria and fungi from developing drug resistance. Therefore, our findings revealed the potential of G21 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.

 

Comments:

The synthesis of bile acid-derived molecules, specifically G21, seems like a breakthrough in combating biofilm infections caused by a variety of microorganisms. G21's broad-spectrum antimicrobial properties, especially its effectiveness against Gram-positive bacteria (GPB), Gram-negative bacteria (GNB), and fungi, make it a promising candidate for addressing chronic infections.

Its mode of action, disrupting microbial cell membranes by interacting with specific components like lipoteichoic acid, lipopolysaccharide, and phosphatidylcholine moieties, showcases its potential to tackle antimicrobial tolerance effectively. Additionally, the ability of G21 to eradicate polymicrobial biofilms and prevent the development of drug resistance is a significant advantage in the fight against persistent infections.

The findings suggest that G21 could serve as a versatile antimicrobial agent with potential applications in treating polymicrobial biofilms and wound infections. Its ability to target multiple types of microorganisms and prevent resistance development positions it as a promising candidate for future therapeutic approaches against biofilm-related infections.

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Cat.No.	Product Name	Information
S4003	Lithocholic acid	Lithocholic acid is a toxic secondary bile acid, causes intrahepatic cholestasis, has tumor-promoting activity, its toxic effect can be protected after it activates the vitamin D receptor, PXR and FXR.

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