Eleutheroside K Isolated from Acanthopanax henryi (Oliv.) Harms Inhibits the Expression of Virulence-Related Exoproteins in Methicillin-Resistant Staphylococcus aureus

Abstract

Methicillin-resistant Staphylococcus (S.) aureus (MRSA) is a representative pathogen that produces numerous virulence factors involving manifold cytotoxins and exotoxins. The present study was designed to investigate the influence of Eleutheroside K (ETSK), a single compound isolated from the leaves of Acanthopanax (A.) henryi (Oliv.) Harms, on the exotoxins secreted by MRSA. The transcription and translation of the exotoxins (α-hemolysin and staphylococcal enterotoxins) related to virulence in S. aureus were determined via quantitative RT-PCR and western blot analysis. The effect of ETSK on the production of tumor necrosis factor (TNF)-α was evaluated using enzyme-linked immunosorbent assay. As a result, ETSK at sub-MIC concentrations could reduce the protein expression of α-hemolysin and enterotoxin, and the expression of genes that regulate virulence factors was also inhibited. In addition, the TNF-inducing activity of S. aureus was attenuated by ETSK in a dose-dependent manner. These results revealed that ETSK not only reduced the protein and gene expression levels of related exotoxins but also suppressed the ability of S. aureus to induce macrophages to release cytokines. This study indicated that the inhibition of MRSA infection by ETSK may be achieved by reducing the virulence of S. aureus and highlighted the potential of ETSK as an innovative strategy for the prevention and treatment of MRSA infections.

Synergistic Antibacterial Activity with Conventional Antibiotics and Mechanism of Action of Shikonin against Methicillin-Resistant Staphylococcus aureus

“…The agr operon is considered to be the quorum sensing regulation system of S. aureus , which can up-regulate the expression of exotoxins such as HLA and SEs [ 27 ]. As the major effector of the agr system, RNAIII positively regulates the expression of virulence factors [ 29 ]. The sae locus is composed of a two-component signal transduction system encoded by saeS and saeR , which can up-regulate the expression of virulence factor genes at the transcription level [ 28 ].…”

“…ELISA was performed using previously described methods [ 29 ]. MRSA DPS-1 strains were cultured in MHB with sub-inhibitory concentrations (1/2 × MIC, 1/4 × MIC, 1/8 × MIC, and 1/16 × MIC) of SKN.…”