title: Flavonols inhibit sortases and sortase-mediated Staphylococcus aureus clumping to fibrinogen.
abstract: 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.
authors.affiliation: Natural Products Research Institute, College of Pharmacy, Seoul National University, Korea.
authors.forename: Sam Sik
authors.initials: SS
authors.lastname: Kang
authors.forename: Jae-Gyu
authors.initials: JG
authors.lastname: Kim
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Lee
authors.forename: Ki-Bong
authors.initials: KB
authors.lastname: Oh
mesh_terms: 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*
chemical_list: D017931:DNA Primers; D004791:Enzyme Inhibitors; D044948:Flavonols; D005340:Fibrinogen; D010458:Peptidyl Transferases