Baicalin inhibits the lethality of Shiga-like toxin 2 in mice.
Shiga-like toxins (Stxs), produced by pathogenic Escherichia coli, are a major virulence factor involved in severe diseases in human and animals. These toxins are ribosome-inactivating proteins, and treatment for diseases caused by them is not available. Therefore, there is an urgent need for agents capable of effectively targeting this lethal toxin. In this study, we identified baicalin, a flavonoid compound used in Chinese traditional medicine, as a compound against Shiga-like toxin 2 (Stx2). We found that baicalin significantly improves renal function and reduces Stx2-induced lethality in mice. Further experiments revealed that baicalin induces the formation of oligomers by the toxin by direct binding. We also identified the residues important for such interactions and analyzed their roles in binding baicalin by biophysical and biochemical analyses. Our results establish baicalin as a candidate compound for the development of therapeutics against diseases caused by Stxs.
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, China.
Jing
J
Dong
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
Yong
Y
Zhang
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Yutao
Y
Chen
Department of Food Quality and Safety, Jilin University, Changchun, China.
Xiaodi
X
Niu
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
Yu
Y
Zhang
College of Pharmacy, NanKai University, Tianjin, China.
Cheng
C
Yang
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Quan
Q
Wang
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China lixm@sun5.ibp.ac.cn dengxm@jlu.edu.cn.
Xuemei
X
Li
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China lixm@sun5.ibp.ac.cn dengxm@jlu.edu.cn.
Xuming
X
Deng
D000818:Animals; D005419:Flavonoids / Q000737:chemistry / Q000627:therapeutic use*; D006367:HeLa Cells; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D022641:Shiga Toxin 2 / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*
D005419:Flavonoids; D022641:Shiga Toxin 2; C038044:baicalin