Bisdemethoxycurcumin Reduces Methicillin-Resistant Staphylococcus aureus Expression of Virulence-Related Exoproteins and Inhibits the Biofilm Formation.

Shu Wang,Dong-Yeul Kwon,Ok-Hwa Kang

doi:10.3390/toxins13110804

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen of nosocomial infection, which is resistant to most antibiotics. Presently, anti-virulence therapy and anti-biofilm therapy are considered to be promising alternatives. In the current work, we investigated the influence of bisdemethoxycurcumin (BDMC) on the virulence-related exoproteins and the biofilm formation using a reference strain and clinic isolated strains. Western blotting, quantitative RT-PCR, and tumor necrosis factor (TNF) release assay were performed to assess the efficacy of BDMC in reducing the expression of Staphylococcus enterotoxin-related exoproteins (enterotoxin A, enterotoxin B) and α-toxin in MRSA. The anti-biofilm activity of BDMC was evaluated through a biofilm inhibition assay. The study suggests that sub-inhibitory concentrations of BDMC significantly inhibited the expression of sea, seb, and hla at the mRNA level in MRSA. Moreover, the expression of virulence-related exoproteins was significantly decreased by down-regulating accessory gene regulator agr, and the inhibition of biofilms formation was demonstrated by BDMC at sub-inhibitory concentrations. Consequently, the study suggests that BDMC may be a potential natural antibacterial agent to release the pressure brought by antibiotic resistance.

Highlights

Methicillin-resistant Staphylococcus aureus (MRSA) is a group of Gram-positive bacteria causing infections in communities and medical institutions worldwide, with a high prevalence and severe drug resistance [1,2]
Key Contribution: In this work, we suggested for the first time that bisdemethoxycurcumin (BDMC), at sub-inhibitory concentrations, significantly decreased the expression of enterotoxin A, enterotoxin
The transcriptional level of the α-toxin gene hla and agrA was quantified by quantitative RT-PCR

Summary

Introduction

Methicillin-resistant Staphylococcus aureus (MRSA) is a group of Gram-positive bacteria causing infections in communities and medical institutions worldwide, with a high prevalence and severe drug resistance [1,2]. Biofilm is a community of microorganisms attached to biotic and abiotic surfaces [9], exhibiting drug resistance to broad-spectrum antibiotics. This biofilm is recalcitrant in efforts to be eradicated by anti-bacterial agents, further limiting the efficacy of currently available antibiotics [10]. The biofilm formation increases MRSA resistance to antibiotics by 10–10,000 times and is the cause of many chronic MRSA infections [13]

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Results

Conclusion