Quercetin targets SarA of methicillin-resistant Staphylococcus aureus to mitigate biofilm formation

Microbiol Spectr. 2024 Jan 11;12(1):e0272223. doi: 10.1128/spectrum.02722-23. Epub 2023 Nov 29.

Abstract

Anti-biofilm is an important strategy against Staphylococcus aureus chronic infection. SarA is a positive regulator of biofilm formation in S. aureus. In this study, we identified the SarA inhibitor quercetin using computer simulation screening. Previous studies have shown that quercetin inhibits biofilm; however, the underlying mechanism remains unknown. This study revealed the inhibitory effect of quercetin on the SarA protein. We also isolated the SarA protein and confirmed its interaction with quercetin in vitro. Besides, the inhibitory effect of quercetin on the transcription and translation levels of the SarA protein was also determined. The effects of quercetin on S. aureus biofilm inhibition and biofilm components were consistent with the changes in the transcription level of biofilm-related genes regulated by SarA. In summary, our study revealed the mechanism by which quercetin affects biofilm formation by inhibiting the transcriptional regulator SarA of S. aureus.

Keywords: anti-biofilm; natural drugs; virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / metabolism
  • Biofilms
  • Computer Simulation
  • Humans
  • Methicillin-Resistant Staphylococcus aureus* / metabolism
  • Quercetin / metabolism
  • Quercetin / pharmacology
  • Staphylococcal Infections* / drug therapy
  • Staphylococcus aureus / metabolism
  • Trans-Activators / genetics
  • Trans-Activators / metabolism

Substances

  • Quercetin
  • Trans-Activators
  • Bacterial Proteins
  • Anti-Bacterial Agents