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.

Highlights

  • Staphylococcus (S.) aureus is a causal organism implicated in considerable opportunistic infections, colonizing humans and animals [1]

  • The downward trend in gene expression of toxicity-related factors suggests that Eleutheroside K (ETSK) may prevent methicillin-resistant S. aureus (MRSA) infection by inhibiting representative exotoxin produced by MRSA

  • This study was devoted to investigating the capability of ETSK isolated from the leaves of A. henryi (Oliv.) Harms to repress the virulence factors released by S. aureus

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Summary

Introduction

Staphylococcus (S.) aureus is a causal organism implicated in considerable opportunistic infections, colonizing humans and animals [1]. Since MRSA is recognized as one of the major causes of healthcare- and Several S. aureus exotoxins produced by MRSA can exacerbate the symptoms of MRSA infections and play a crucial role in the pathogenesis, including hemolysins, enterotoxins, toxic shock syndrome toxin 1 (TSST-1) and panton–valentine leukocidin (PVL) [9]. These toxins are related to the increased inflammation and disease severity of S. aureus infection. The global regulatory systems such as accessory gene regulators (agr) system control the expression of S. aureus toxins [10]. The agr locus is considered to be the quorum-sensing

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