Differential binding of Shiga toxin 2 to human and murine neutrophils

Abstract

Shiga toxins (Stx1 and Stx2) are responsible for initiating haemolytic uraemic syndrome, a serious extraintestinal complication caused by enterohaemorrhagic Escherichia coli O157 : H7 infection in humans. Shiga toxins are classical AB(5)-type exotoxins, consisting of a globotriaosylceramide (Gb(3))-binding B subunit pentamer and an enzymic A subunit. It is demonstrated in this study that Stx2 binds to human neutrophils by a non-classical mechanism that is independent of Gb(3). In contrast, the investigation revealed that Stx2 binds to murine neutrophils by the classical Gb(3)-dependent mechanism. Moreover, whereas the human serum amyloid P (HuSAP) component inhibited Stx2 binding to murine neutrophils, HuSAP increased Stx2 binding to human neutrophils by 84.2 % (P< or =0.002, Student's t-test). These observations may explain why HuSAP protects mice from the lethal effects of Stx2, whereas there is no indication that HuSAP plays a similar protective role in humans infected by E. coli O157 : H7.