title: Quercitrin, an inhibitor of Sortase A, interferes with the adhesion of Staphylococcal aureus.
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.
authors: College of Animal Science, Jilin University, Changchun 130062, China. lhglbr@outlook.com.
authors: Bingrun
authors: B
authors: Liu
authors: College of Animal Science, Jilin University, Changchun 130062, China. chenfuguang@caas.cn.|State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute of Chinese Academy of Agricultural Science, Harbin 150001, China. chenfuguang@caas.cn.
authors: Fuguang
authors: F
authors: Chen
authors: College of Animal Science, Jilin University, Changchun 130062, China. bicwei@163.com.
authors: Chongwei
authors: C
authors: Bi
authors: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China. chj6788571@163.com.
authors: Lin
authors: L
authors: Wang
authors: College of Animal Science, Jilin University, Changchun 130062, China. 15043029208@163.com.
authors: Xiaobo
authors: X
authors: Zhong
authors: College of Animal Science, Jilin University, Changchun 130062, China. chj6788571@163.com.
authors: Hongjun
authors: H
authors: Cai
authors: Key Laboratory of Zoonosis Research, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun 130062, China. dengxm@jlu.edu.cn.
authors: Xuming
authors: X
authors: Deng
authors: Department of Food Quality and Safety, Jilin University, Changchun130062, China. niuxd@jlu.edu.cn.
authors: Xiaodi
authors: X
authors: Niu
authors: College of Animal Science, Jilin University, Changchun 130062, China. wangdc@jlu.edu.cn.
authors: Dacheng
authors: D
authors: Wang
mesh_terms: D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology; D001422:Bacterial Adhesion / Q000187:drug effects*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D002384:Catalysis / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; C012526:quercitrin; D011794:Quercetin; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases