Abstract
Sortase A (SrtA) is a cysteine transpeptidase of most Gram-positive bacteria that is responsible for the anchorage of many surface protein virulence factors to the cell wall layer. SrtA mutants are unable to display surface proteins and are defective in the establishment of infections without affecting microbial viability. In this study, we report that quercitrin (QEN), a natural compound that does not affect Staphylococcus aureus growth, can inhibit the catalytic activity of SrtA in fibrinogen (Fg) cell-clumping and immobilized fibronectin (Fn) adhesion assays. Molecular dynamics simulations and mutagenesis assays suggest that QEN binds to the binding sites of the SrtA G167A and V193A mutants. These findings indicate that QEN is a potential lead compound for the development of new anti-virulence agents against S. aureus infections.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Aminoacyltransferases / antagonists & inhibitors*
-
Aminoacyltransferases / chemistry
-
Aminoacyltransferases / metabolism
-
Anti-Bacterial Agents / chemistry
-
Anti-Bacterial Agents / pharmacology
-
Bacterial Adhesion / drug effects*
-
Bacterial Proteins / antagonists & inhibitors*
-
Bacterial Proteins / chemistry
-
Bacterial Proteins / metabolism
-
Binding Sites
-
Catalysis / drug effects
-
Cysteine Endopeptidases / chemistry
-
Cysteine Endopeptidases / metabolism
-
Enzyme Activation / drug effects
-
Enzyme Inhibitors / chemistry
-
Enzyme Inhibitors / pharmacology
-
Microbial Sensitivity Tests
-
Models, Molecular
-
Molecular Conformation
-
Protein Binding
-
Quercetin / analogs & derivatives*
-
Quercetin / chemistry
-
Quercetin / pharmacology
-
Staphylococcus aureus / drug effects*
-
Staphylococcus aureus / physiology*
Substances
-
Anti-Bacterial Agents
-
Bacterial Proteins
-
Enzyme Inhibitors
-
quercitrin
-
Quercetin
-
Aminoacyltransferases
-
sortase A
-
Cysteine Endopeptidases