Facially Amphiphilic Bile Acid-Functionalized Antimicrobials: Combating Pathogenic Bacteria, Fungi, and Their Biofilms

Abstract

We report facially amphiphilic bile acid-based antimicrobials with a broad spectrum of activity against both bacterial and fungal pathogens and negligible detrimental effects on mammalian cells. Two lead compounds eliminated dormant subpopulations of various bacterial species, unlike conventional antibiotics. The lead compounds were also effective in eradicating biofilms of methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), <i>Pseudomonas aeruginosa</i>, and <i>Candida albicans</i>. Additionally, these compounds substantially inhibited the formation of fungal biofilms (<i>C. albicans</i>). Mechanistic investigations revealed the membrane-active nature and endogenous reactive oxygen species (ROS) induction ability of these compounds. Finally, no detectable resistance was developed by the bacterial strains against this class of membrane-targeting antimicrobials.