Bile Acid Oligomers and Their Combination with Antibiotics To Combat Bacterial Infections

The
ever-growing risk of bacterial resistance is a critical concern. Among
the various antimicrobial resistant bacterial strains, methicillin
and vancomycin resistant Staphylococcus aureus are among the most dreadful, causing serious complications. On the
basis of the hypothesis that microbes have reduced ability to develop
resistance against membrane targeting antibiotics, bile acid oligomers
having unique facially amphiphilic topologies were designed and synthesized.
The oligomers with specific linkers exhibited potent and selective
antibacterial activity against Gram-positive bacteria. The lead compounds
also improved the efficacy of a range of known antibiotics belonging
to different classes when tested in combination. The active dimers
were found to be effective against antibiotic-resistant clinical isolates
of S. aureus, including multidrug resistant
isolates. A significant inhibitory activity against S. aureus biofilm, a highly drug-resistant bacterial
phenotype often unresponsive to antibiotic therapy, was also noticed.
No adverse effects were observed by these dimers in a cell viability
assay against HEK293 cells.