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Bisdemethoxycurcumin Reduces Methicillin-Resistant Staphylococcus aureus Expression of Virulence-Related Exoproteins
Shu Wang1, Ok-Hwa Kang1, Dong-Yeul Kwon1
1Department of Oriental Pharmacy, College of Pharmacy and Wonkwang Oriental Medicines Research Institute, Wonkwang University, Iksan 54538, Jeonbuk, Korea.
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.
Insights
Bisdemethoxycurcumin (BDMC) effectively reduces virulence factors and biofilm formation in Methicillin-resistant Staphylococcus aureus (MRSA). This natural compound shows promise as an alternative antibacterial agent against antibiotic-resistant strains.
Area of Science:
- Microbiology
- Pharmacology
- Natural Products Chemistry
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) is a significant cause of hospital-acquired infections, exhibiting resistance to conventional antibiotics.
- Anti-virulence and anti-biofilm therapies are emerging as promising strategies to combat MRSA infections.
- Bisdemethoxycurcumin (BDMC), a derivative of curcumin, is being explored for its potential therapeutic properties.
Purpose of the Study:
- To investigate the effects of BDMC on virulence-related exoproteins and biofilm formation in MRSA.
- To evaluate BDMC's efficacy in reducing the expression of key MRSA virulence factors, including staphylococcal enterotoxins and alpha-toxin.
- To assess BDMC's anti-biofilm activity against both reference and clinical MRSA strains.
Main Methods:
- Western blotting and quantitative RT-PCR were used to measure the expression levels of virulence factors and their corresponding genes.
- Tumor necrosis factor (TNF) release assay was performed to assess the impact of BDMC on inflammatory responses.
- Biofilm inhibition assays were conducted to evaluate BDMC's effectiveness in preventing biofilm formation.
Main Results:
- Sub-inhibitory concentrations of BDMC significantly suppressed the mRNA expression of staphylococcal enterotoxin A (sea), enterotoxin B (seb), and alpha-toxin (hla) in MRSA.
- BDMC treatment led to a significant decrease in the expression of virulence-related exoproteins.
- Down-regulation of the accessory gene regulator (agr) was observed, contributing to reduced virulence factor expression.
- BDMC demonstrated significant inhibition of biofilm formation in MRSA at sub-inhibitory concentrations.
Conclusions:
- BDMC effectively inhibits MRSA virulence factor production and biofilm formation.
- The compound acts, in part, by down-regulating the accessory gene regulator (agr) pathway.
- BDMC represents a potential natural antibacterial agent for mitigating the challenges posed by antibiotic resistance in MRSA infections.
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