AUTHOR=Hua Xin , Yang Qin , Zhang Wanjiang , Dong Zhimin , Yu Shenye , Schwarz Stefan , Liu Siguo 

TITLE=Antibacterial Activity and Mechanism of Action of Aspidinol Against Multi-Drug-Resistant Methicillin-Resistant Staphylococcus aureus

JOURNAL=Frontiers in Pharmacology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00619

DOI=10.3389/fphar.2018.00619

ISSN=1663-9812

ABSTRACT=<p>This study aimed at investigating the antibacterial activity of aspidinol, an extract from <italic>Dryopteris fragrans</italic> (L.) Schott, against methicillin-resistant <italic>Staphylococcus aureus</italic> (MRSA). MRSA isolates were treated with aspidinol to determine the differential expression of genes and associated pathways following the drug treatment. Aspidinol displayed significant anti-MRSA activity, both <italic>in vivo</italic> (minimum inhibitory concentration = 2 μg/mL) and <italic>in vitro</italic>, and achieved an antibacterial effect comparable to that of vancomycin. In the lethal septicemic mouse study, a dose of 50 mg/kg of either aspidinol or vancomycin provided significant protection from mortality. In the non-lethal septicemic mouse study, aspidinol and vancomycin produced a significant reduction in mean bacterial load in murine organs, including the spleen, lung, and liver. After treatment with aspidinol, we found through RNA-seq and RT-PCR experiments that the inhibition of the formation of ribosomes was the primary <italic>S. aureus</italic> cell-killing mechanism, and the inhibition of amino acid synthesis and the reduction of virulence factors might play a secondary role.</p>