n-chlorotaurine, a long-lived oxidant produced by human leukocytes, inactivates shiga toxin of enterohemorrhagic escherichia coli牛磺酸衍生物,长寿氧化剂由人类白细胞,志贺毒素肠出血性大肠杆菌的灭活.pdfVIP

N-Chlorotaurine, a Long-Lived Oxidant Produced by Human Leukocytes, Inactivates Shiga Toxin of Enterohemorrhagic Escherichia coli 1 1 2 2 1 Christian Eitzinger , Silvia Ehrlenbach , Herbert Lindner , Leopold Kremser , Waldemar Gottardi , 3 3 1 . 1. Dmitri Debabov , Mark Anderson , Markus Nagl * , Dorothea Orth 1 Department of Hygiene, Microbiology and Social Medicine, Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Innsbruck, Austria, 2 Division of Clinical Biochemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria, 3 NovaBay Pharmaceuticals, Inc., Emeryville, California, United States of America Abstract N-chlorotaurine (NCT), the main representative of long-lived oxidants produced by granulocytes and monocytes, is known to exert broad-spectrum microbicidal activity. Here we show that NCT directly inactivates Shiga toxin 2 (Stx2), used as a model toxin secreted by enterohemorrhagic Escherichia coli (EHEC). Bacterial growth and Stx2 production were both inhibited by 2 mM NCT. The cytotoxic effect of Stx2 on Vero cells was removed by $5.5 mM NCT. Confocal microscopy and FACS analyses showed that the binding of Stx2 to human kidney glomerular endothelial cells was inhibited, and no NCT- treated Stx2 entered the cytosol. Mass spectrometry displayed oxidation of thio groups and aromatic amino acids of Stx2 by NCT. Therefore, long-lived oxidants may act as powerful tools of innate immunity against soluble virulence factors of pathogens. Moreover, inactivation of virulence factors may contribute to therapeutic success of NCT and novel analogs,