Reversal of Multi-Drug Resistance in Staphylococcus aureus by Natural Product-Way Forward

The emergence of antibiotic resistance has made most of the first-line antibiotics ineffective. The search of novel antimicrobial entities is, therefore, vigorously pursued. We report here the resistance reversal potential of a monoterpene, tschimganin (1), against various strains of MDR Staphylococcus aureus. Compound 1 was isolated from Ferula ovina (Bioss). Bioss. By using flow cytometry, the bacterial cell membrane depolarization by tschimganin (1) was studied. Lucigenin chemiluminescence assay was employed to evaluate the generation of reactive oxygen species (ROS) in multi-drug resistant (MDR) bacterial cells. The reversal of multi-drug resistance by tschimganin (1), in combination with selected antibiotics, was also evaluated through fractional inhibitory concentration index (FICI) assay. The ultra-structural changes in bacterial cells after the treatment of tschimganin (1) were studied by using scaning and transmission electron microscopy. The anti-bacterial activity of tschimganin (1) in the presence of blood (ex vivo) was also studied. Tschimganin (1) facilitates the anionic probe to enter in to the depolarized bacterial cell membrane and binds with the lipid rich cellular components. Most importantly, it reverse the drug resistance and augment the sensitivity of already failed drugs by lowering their minimum inhibitory concentrations (MICs). Monoterpene, tschimganin (1) (Ferula ovina (Bioss). Bioss) was thus identified as a new resistance reversal agent against multi-drug resistant Staphylococcus aureus.