Antibacterial Activity And Mechanism Of Action Of Aspidinol Against Multi-Drug-Resistant Methicillin-resistant Staphylococcus Aureus

Overuse of antibiotics in human diseases treatment and livestock production resulted in unprecedented severe problem of bacterial drug resistance.The especially serious one is the increasing clinical isolation of methicillin-resistant Staphylococcus aureus(MRSA),which cause serious infection and disease in livestock and poultry production.At present,however,effective drug for MRSA treatment is only limited in the veterinary clinical.Hence,prevention and control of MRSA has become the current focus in the field of prevention and treatment of bacterial infection around the world.In this study,aspidinol was evaluated for its anti-MRSA activities and the mechanism behind the activities was investigated,using the reference MRSA strain(ATCC33591)and clinical isolates as targets.The minimum inhibition concentration(MIC)and minimum bactericidal concentration(MBC)were determined by the method of micro broth dilution.According to the results of MIC and MBC,the dynamic anti-MRSA effect of aspidinol was evaluated,and the MRSA-killing curve was graphed to obtain the optimal concentration and time for the best efficacy of aspidinol.In vivo experiments were performed with mouse sepsis model for protection test and treatment test by aspidinol.The results confirmed that aspidinol has clear anti-MRSA activity both in vivo and in vitro.To clarify the key pathways involved in the anti-MRSA activity of aspidinol,transcriptome sequencing technology was used.We compared the transcriptome data of MRSA strains before and after aspidinol treatment,then determined the key pathways involved in anti-MRSA activity of aspidinol.The involvement of these pathways was further confirmed by real-time quantitative PCR.The results above indicated that aspidinol has significant anti-MRSA activity both in vivo and in vitro,and that colud be attributed to the inhibition of P-lactam resistance pathway,amino acid pathway,pathogenicity pathway,ferritin synthesis and ribosome on the key genes.