In vitro antimicrobial and antibiofilm activity of ursolic acid and its amide derivatives against Acinetobacter baumannii

Abstract

Background: Nosocomial infections due to biofilm-producing ESKAPE pathogens have raised globally. Acinetobacter baumannii is one of the members of ESKAPE pathogens and it's spreading widely and becomes more problematic to treat and managed in health care settings and in the community due to multidrug resistance. WHO categorizes A. baumannii among the pathogens for which new pharmacophores required on an urgent basis. Compounds from medicinal plants can be a source to developed novel antimicrobial agents against high-risk A.baumannii infections. Ursolic acid and its synthetic amide derivatives emerge as a new class of antimicrobial agents for treating multi drug-resistant infections. Methods and materials: To find out the antimicrobial and antibiofilm activity, we used the standard culture of A.baumannii (ATCC: 19606) and its colistin resistance strains. The antimicrobial and biofilm inhibiting activity of these compounds was evaluated by using the microdilution method, crystal violet assay, time-kill assays, post antimicrobial assays, cytotoxic activity, microscopic (light & Atomic force microscope) evaluation, and gene expression analysis. Results: The selected compound possesses antimicrobial and antibiofilm activity against the standard and colistin-resistant clinical isolates of A.baumannii. At MIC (77.87 μg/ml) of compound, it inhibits more than 65% of biofilm formation and eradicates more than 63% of pre-form biofilm. Amide derivate of ursolic acid effectively inhibits the biofilm formation as well as eradicated the preformed biofilms by killing bacterial cells. Furthermore, atomic force microscopy showed the disruption of cell membrane which might be the reason for antimicrobial activity. Gene expression analysis showed the significant downregulation of biofilm-forming genes (abaR and bap). Conclusion: So, ursolic acid and its amide derivative might be used to tackle Acinetobacter baumannii related nosocomial infections and further evaluated as a drug candidate.