Cholic-Acid-Derived Amphiphiles Can Prevent and Degrade Fungal Biofilms

Area of Science:

• Mycology
• Medicinal Chemistry
• Biomaterials

Background:

• Fungal infections, particularly from Candida species, pose significant health risks due to biofilm formation on medical devices, leading to organ damage.
• Candida species exhibit resistance to host immune responses and existing antifungal drugs, necessitating novel therapeutic strategies.
• Targeting fungal cell membranes presents a viable alternative approach to combatting these infections.

Purpose of the Study:

• To screen cholic acid-derived amphiphiles as potential membrane-targeting agents against Candida strains.
• To evaluate the structure-activity relationship, efficacy, and safety of these novel amphiphiles.
• To assess their potential in preventing and eradicating fungal biofilms and treating infections in preclinical models.

Main Methods:

• Screening of various cholic acid-based amphiphiles against different Candida strains.
• Structure-activity correlation analysis, biochemical assays, and electron microscopy.
• In vitro biofilm inhibition and degradation assays, in vivo murine models for wound infection and device-associated biofilm prevention.

Main Results:

• Amphiphiles with 4 and 6 carbon chains demonstrated potent, safe membrane-targeting activity against Candida species.
• Unlike fluconazole, repeated exposure to these amphiphiles did not induce drug resistance in Candida albicans.
• These amphiphiles effectively prevented biofilm formation and degraded pre-existing biofilms on various substrates, including acrylic teeth.
• In murine models, amphiphiles 4 and 6 cleared Candida albicans wound infections and prevented biofilm formation on indwelling devices.

Conclusions:

• Cholic acid-derived amphiphiles are effective membrane-targeting antimycotic agents.
• These compounds represent a promising alternative for preventing and treating Candida infections, including those associated with biofilms on medical devices.
• The developed amphiphiles and their coatings offer a viable strategy to overcome drug resistance and manage challenging fungal infections.