Quercitrin, an Inhibitor of Sortase A, Interferes with the Adhesion of Staphylococcal aureus

被引:40
作者
Liu, Bingrun [1 ]
Chen, Fuguang [1 ,2 ]
Bi, Chongwei [1 ]
Wang, Lin [3 ]
Zhong, Xiaobo [1 ]
Cai, Hongjun [1 ]
Deng, Xuming [3 ]
Niu, Xiaodi [4 ]
Wang, Dacheng [1 ]
机构
[1] Jilin Univ, Coll Anim Sci, Changchun 130062, Peoples R China
[2] Chinese Acad Agr Sci, Harbin Vet Res Inst, State Key Lab Vet Biotechnol, Harbin 150001, Peoples R China
[3] Jilin Univ, Inst Zoonosis, Coll Vet Med, Key Lab Zoonosis Res,Minist Educ, Changchun 130062, Peoples R China
[4] Jilin Univ, Dept Food Qual & Safety, Changchun 130062, Peoples R China
关键词
sortase A; quercitrin; Staphylococcus aureus; molecular modeling; SURFACE-PROTEINS; CELL-WALL; TRANSPEPTIDASE; IDENTIFICATION; INFECTIONS; DISCOVERY; BACTERIA; AGENTS; TARGET;
D O I
10.3390/molecules20046533
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:6533 / 6543
页数:11
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