Shiga Toxin (Stx) Type 1a Reduces the XXXX of Stx Type 2a.

@entity137 @entity72629 @entity19 @entity526 @entity204 @entity72628
BACKGROUND: Shiga toxin (Stx) is the primary virulence factor of Stx-producing @entity526 (STEC). STEC can produce @entity72628 and/or Stx2a, which are antigenically distinct. However, Stx2a-producing STEC are associated with more severe disease than strains producing both @entity72628 and Stx2a. METHODS AND RESULTS: To address the hypothesis that the reason for the association of Stx2a with more severe disease is because Stx2a crosses the intestinal barrier with greater efficiency that @entity72628 , we covalently labeled @entity72628 and Stx2a with @entity72629 and determined the ex vivo fluorescent intensity of @entity19 systemic organs after oral intoxication. Surprisingly, both Stxs exhibited similar dissemination patterns and accumulated in the kidneys. We next cointoxicated @entity19 to determine whether @entity72628 could impede Stx2a. Cointoxication resulted in increased survival and an extended mean time to @entity204 , compared with intoxication with Stx2a only. The survival benefit was dose dependent, with the greatest effect observed when 5 times more @entity72628 than Stx2a was delivered, and was amplified when @entity72628 was delivered 3 hours prior to Stx2a. Cointoxication with an @entity72628 active site toxoid also reduced Stx2a @entity137 . CONCLUSIONS: These studies suggest that @entity72628 reduces Stx2a-mediated @entity137 , a finding that may explain why STEC that produce only Stx2a are associated with more severe disease than strains producing @entity72628 and Stx2a.
