Investigating the Antimicrobial Activity of Asiatic Acid Derivatives against Clostridium difficile

Abstract

Clostridium difficile infection (CDI) is a healthcare-associated gastrointestinal infection caused by Clostridium difficile (C. difficile), an anaerobic spore-forming gram-positive bacterium. The primary treatment for CDI is using antibiotics such as metronidazole and vancomycin. However, both drugs are reported to be less effective against C. difficile due to resistance. Several natural products such as asiatic acid (AA) and its derivatives have shown promising antimicrobial properties against C. difficile. In this study, the antimicrobial activity of AA and its derivatives such as AT1, LS1, and LS2 were investigated against C. difficile 630 and R20291 using the minimal inhibitory concentration (MIC) and time-kill kinetic assay. AA showed an inhibitory effect against C. difficile 630 and R20291 with MIC value 20 μg/ml. Meanwhile, LS1 showed an inhibitory effect against C. difficile 630 and R2091 with MIC values of 10 and 10-15 μg/ml, respectively. Similarly, LS2 showed an inhibitory effect against C. difficile 630 and R20291 with MIC values of 10-15 and 15-20 μg/ml. Consistently, both LS1 and LS2 showed an inhibitory effect against C. difficile 630 and R20291 over time with a dose-dependent effect in all concentrations for the time-kill kinetic assay. Meanwhile, AA only showed slight inhibition against C. difficile R20291 in concentration 20 μg/ml, while AT1 did not show any inhibition at all concentrations for both experiments. In conclusion, AA derivatives LS1 and LS2 have a high potential inhibitory effect against C. difficile 630 and R20291, while AT1 does not.