M E Del Cogliano, A Pinto, C I Rivero, A Bernal, R J Fernández-Brando, J Goldstein, L C S Ferreira, M S Palermo, L V Bentancor
Shiga toxin-producing Escherichia coli (STEC) is a major cause of foodborne disease and hemolytic uremic syndrome (HUS), a severe condition for which no specific therapies are currently available. The major virulence factor of STEC is Shiga toxin 2 (Stx2), which is encoded by the Stx2-converting bacteriophage 933 W used in this study, and phage induction plays a central role in toxin release and disease progression.In this study, we evaluated the protective in vivo effects of bismuth hydroxide gel (BHOG), a low-cost gastrointestinal compound with previously described antimicrobial and anti-toxin activities, in a murine model of STEC infection driven by the Stx2-converting bacteriophage 933 W. Mice treated with BHOG showed significantly higher survival rates compared than untreated controls (P = 0.0115), together with preservation of renal function, evidenced by significantly lower blood urea nitrogen and plasma urea levels (P < 0.05). Histological analysis demonstrated significantly reduced intestinal and renal tissues damage in treated animals compared with untreated controls. Overall, our findings provide in vivo evidence supporting a protective effect of BHOG against Shiga toxin-mediated disease. This study suggests that bismuth-based compounds may represent a potential adjunct to, or an alternative strategy for, the management of STEC-associated disease.