Antibody-based protection of gnotobiotic piglets infected with Escherichia coli O157:H7 against systemic complications associated with Shiga toxin 2

Abstract

Hemolytic-uremic syndrome (HUS) is a serious disease in children, attributable in the majority of cases to infection with Shiga toxin (Stx)-producing Escherichia coli. Using gnotobiotic piglets orally infected with E. coli O157:H7, which develop Stx-related cerebellar lesions and fatal neurological symptoms, we show that administration of Stx2-specific antiserum well after challenge protected, in a dose-response fashion, against these symptoms for at least 24 h after bacterial challenge. Twenty-six of 30 piglets given Stx2 antiserum survived the challenge, compared to only 4 of 16 animals given control serum or saline. Given our observations in piglets, Stx antibody of human origin may likewise prevent HUS in children.

FIG. 1

Section through the large intestine of a piglet challenged orally with E. coli O157:H7 strain 86-24 4 days earlier. A disrupted colonic surface damaged by bacterial attachment and effacement seen in the middle, with no evidence of inflammation. The mucosa on either side of the lesion looks still intact (hematoxylin and eosin; original magnification, ×400).

FIG. 2

Section through the cerebellum of a piglet challenged orally with E. coli O157:H7 strain 86-24, which produces Stx2, showing focal hemorrhages (arrows) in the molecular and granular layers (hematoxylin and eosin; original magnification, ×400).