Flavonols inhibit sortases and sortase-mediated Staphylococcus aureus clumping to fibrinogen.
Sortases are a family of Gram-positive transpeptidases responsible for anchoring surface protein virulence factors to the peptidoglycan cell wall layer. In Staphylococcus aureus, deletion of the sortase isoforms results in marked reduction in virulence and infection potential, making it an important antivirulence target. We examined the effects of naturally occurring flavonols on recombinant sortase A (SrtA) and B (SrtB) prepared from S. aureus ATCC6538p and found that these compounds inhibited the activity of sortases, without exhibiting antibacterial activities. Among the flavonols tested, morin, myricetin, and quercetin exhibited strong sortase inhibitory activities (SrtA IC50: 37.39-52.70 microM, SrtB IC50: 8.54-36.89 microM). The fibrinogen cell-clumping activity data highlight the potential of flavonols for the treatment of S. aureus infections via inhibition of sortase.
Kang
Sam Sik
SS
Natural Products Research Institute, College of Pharmacy, Seoul National University, Korea.
Kim
Jae-Gyu
JG
Lee
Tae-Hoon
TH
Oh
Ki-Bong
KB
D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects*; D017931:DNA Primers; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005340:Fibrinogen / Q000378:metabolism*; D044948:Flavonols / Q000494:pharmacology*; D010458:Peptidyl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013211:Staphylococcus aureus / Q000378:metabolism*
D017931:DNA Primers; D004791:Enzyme Inhibitors; D044948:Flavonols; D005340:Fibrinogen; D010458:Peptidyl Transferases