Probing Antimicrobial Activity and Mechanism of Action of a Bile Acid-Derived Antibiotic

Antibiotics have revolutionized medicine, saving countless lives since the introduction of penicillin. However, antimicrobial resistance has challenged their efficacy, prompting ongoing efforts to develop new antibiotics. This study explores the antimicrobial effects of a bile acid derivative, BA-3/4-Butyl. By analyzing the interactions of BA-3/4-Butyl with model bacterial (DOPC/DOPG) and mammalian (DOPC/cholesterol) membranes and by probing its mechanism of action against bacteria using a variety of assays and transmission electron microscopy (TEM) imaging, we reveal that BA-3/4-Butyl exerts its antimicrobial activity via membrane permeabilization. Our findings provide insights into how BA-3/4-Butyl compromises bacterial membranes without causing toxicity in its mammalian counterparts. This study advances the understanding of BA-3/4-Butyl's antimicrobial activity and potential mechanisms of action, ultimately aiding the development of similar novel therapeutic agents to help combat antimicrobial resistance.