Cholic Acid-Derived Amphiphile can Combat Gram-Positive Bacteria-mediated Infections via Disintegration of Lipid Clusters

Inappropriate and uncontrolled use of antibiotics results in emergence of antibiotic resistance, thereby threatening the present clinical regimens to treat infectious diseases. Therefore, new antimicrobial agents that can prevent the bacteria to develop drug resistance are urgently needed. Selective disruption of bacterial membranes is the most effective strategy for combating microbial infections as accumulation of the genetic mutations cannot allow the emergence of drug resistance against these antimicrobials. In this work, we tested the cholic acid (CA)-derived amphiphiles tethered with different alkyl chains for their ability to combat gram-positive bacterial infections. In-depth biophysical and biomolecular simulation studies suggested that the amphiphile with hexyl chain (6) executes more effective interactions with gram-positive bacterial membranes as compared to other hydrophobic counterparts. Amphiphile 6 is effective against multi-drug resistant gram-positive bacterial strains as well and does n...