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Flavonols inhibit sortases and sortase-mediated Staphylococcus aureus clumping to fibrinogen

Sam Sik Kang1, Jae-Gyu Kim, Tae-Hoon Lee

  • 1Natural Products Research Institute, College of Pharmacy, Seoul National University, Korea.

Biological & Pharmaceutical Bulletin
|August 2, 2006
PubMed

Insights

Naturally occurring flavonols inhibit Staphylococcus aureus sortases (SrtA and SrtB), key virulence factors. These compounds show potential for treating S. aureus infections by targeting sortase activity without causing antibacterial effects.

Area of Science:

  • Microbiology
  • Biochemistry
  • Pharmacology

Background:

  • Sortases are Gram-positive bacterial transpeptidases essential for anchoring surface proteins to the cell wall.
  • In Staphylococcus aureus, sortase activity is crucial for virulence, making it a significant antivirulence target.
  • Flavonols are natural compounds with diverse biological activities.

Purpose of the Study:

  • To investigate the inhibitory effects of naturally occurring flavonols on recombinant Staphylococcus aureus sortase A (SrtA) and sortase B (SrtB).
  • To evaluate the potential of these flavonols as therapeutic agents against S. aureus infections by targeting sortase activity.

Main Methods:

  • Preparation of recombinant SrtA and SrtB from S. aureus ATCC6538p.
  • Enzyme inhibition assays to determine the IC50 values of various flavonols against SrtA and SrtB.
  • Assessment of fibrinogen cell-clumping activity to evaluate the functional impact of sortase inhibition.

Main Results:

  • Morin, myricetin, and quercetin demonstrated significant inhibitory activity against both SrtA and SrtB.
  • Specific IC50 values were determined: SrtA IC50 ranged from 37.39-52.70 microM, and SrtB IC50 ranged from 8.54-36.89 microM.
  • The tested flavonols did not exhibit direct antibacterial activity but effectively inhibited sortase-mediated cell clumping.

Conclusions:

  • Naturally occurring flavonols, particularly morin, myricetin, and quercetin, are potent inhibitors of Staphylococcus aureus sortases.
  • Flavonols represent a promising class of compounds for developing novel antivirulence therapies against S. aureus infections by targeting sortase activity.

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