Quercitrin, an Inhibitor of Sortase A, Interferes with the Adhesion of Staphylococcal aureus
Bingrun Liu,
Fuguang Chen,
Chongwei Bi,
Lin Wang,
Xiaobo Zhong,
Hongjun Cai,
Xuming Deng,
Xiaodi Niu,
Dacheng Wang
Affiliations
Bingrun Liu
College of Animal Science, Jilin University, Changchun 130062, China
Fuguang Chen
College of Animal Science, Jilin University, Changchun 130062, China
Chongwei Bi
College of Animal Science, Jilin University, Changchun 130062, China
Lin Wang
Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China
Xiaobo Zhong
College of Animal Science, Jilin University, Changchun 130062, China
Hongjun Cai
College of Animal Science, Jilin University, Changchun 130062, China
Xuming Deng
Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China
Xiaodi Niu
Department of Food Quality and Safety, Jilin University, Changchun130062, China
Dacheng Wang
College of Animal Science, Jilin University, Changchun 130062, China
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.
