Study on Demethoxycurcumin as a Promising Approach to Reverse Methicillin-Resistance of Staphylococcus aureus

Int J Mol Sci. 2021 Apr 6;22(7):3778. doi: 10.3390/ijms22073778.

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) has always been a threatening pathogen. Research on phytochemical components that can replace antibiotics with limited efficacy may be an innovative method to solve intractable MRSA infections. The present study was devoted to investigate the antibacterial activity of the natural compound demethoxycurcumin (DMC) against MRSA and explore its possible mechanism for eliminating MRSA. The minimum inhibitory concentrations (MICs) of DMC against MRSA strains was determined by the broth microdilution method, and the results showed that the MIC of DMC was 62.5 μg/mL. The synergistic effects of DMC and antibiotics were investigated by the checkerboard method and the time-kill assay. The ATP synthase inhibitors were employed to block the metabolic ability of bacteria to explore their synergistic effect on the antibacterial ability of DMC. In addition, western blot analysis and qRT-PCR were performed to detect the proteins and genes related to drug resistance and S. aureus exotoxins. As results, DMC hindered the translation of penicillin-binding protein 2a (PBP2a) and staphylococcal enterotoxin and reduced the transcription of related genes. This study provides experimental evidences that DMC has the potential to be a candidate substance for the treatment of MRSA infections.

Keywords: MRSA; PBP2a; anti-bacterial activity; demethoxycurcumin; methicillin-resistant Staphylococcus aureus; synergistic effect; β-lactam antibiotic.

MeSH terms

  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism*
  • Diarylheptanoids / pharmacology*
  • Gene Expression Regulation, Bacterial / drug effects*
  • Humans
  • Methicillin Resistance / drug effects*
  • Methicillin-Resistant Staphylococcus aureus / genetics
  • Methicillin-Resistant Staphylococcus aureus / metabolism*
  • Penicillin-Binding Proteins / genetics
  • Penicillin-Binding Proteins / metabolism*
  • Staphylococcal Infections / drug therapy

Substances

  • Bacterial Proteins
  • Diarylheptanoids
  • Penicillin-Binding Proteins
  • mecA protein, Staphylococcus aureus
  • demethoxycurcumin

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