Abstract
This study aimed at investigating the antibacterial activity of aspidinol, an extract from Dryopteris fragrans (L.) Schott, against methicillin-resistant Staphylococcus aureus (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 in vivo (minimum inhibitory concentration = 2 μg/mL) and in vitro, 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 S. aureus cell-killing mechanism, and the inhibition of amino acid synthesis and the reduction of virulence factors might play a secondary role.
Highlights
Methicillin-resistant Staphylococcus aureus (MRSA) is the most common pathogen and is associated with high morbidity and mortality in both humans and animals (VanEperen and Segreti, 2016)
Cytotoxicity tests indicated that the toxicity of aspidinol toward macrophage cells (RAW264.7) was negligible
As aspidinol exhibited potent anti-methicillin-resistant Staphylococcus aureus (MRSA) activity, we explored the ability of aspidinol to permeate cellular membranes and kill MRSA located inside eukaryotic cells
Summary
Methicillin-resistant Staphylococcus aureus (MRSA) is the most common pathogen and is associated with high morbidity and mortality in both humans and animals (VanEperen and Segreti, 2016). MRSA causes nosocomial infections, pneumonia (Woods and Colice, 2014), sepsis (Taylor, 2013), and skin infections (Mihu et al, 2015). In January 2017, MRSA was officially ranked as one of the 12 deadliest drug-resistant bacteria by WHO (2017). Antibiotics are the most effective tool to combat infections due to pathogenic bacteria. While new antimicrobial agents are becoming increasingly difficult to develop, medicine is currently unable to keep pace with the emergence of resistant bacteria (Rennie, 2012). It is imperative to develop new agents to fight resistant bacteria, especially MRSA
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