Evaluating the protective effects of Aurodox in a murine model of Shiga toxin-producing Escherichia coli.

Abstract

Shiga Toxin-Producing E. coli (STEC) are a group of acute small intestine pathogens responsible for foodborne outbreaks of bloody diarrhoea. The expression of Shiga toxins (Stx) carried by STEC can initiate Haemolytic Uremic Syndrome (HUS), a major cause of acute renal failure in children. Here, we investigate the anti-virulence potential of Aurodox - a natural product of Streptomyces goldiniensis. Previously, we have shown that Aurodox downregulates the expression of the T3SS, inhibiting epithelial cell colonisation in vitro. Here, we use the Citrobacter rodentium DBS770 (Cr Stx2_dact) model of STEC infection to demonstrate that Aurodox protects mice against Citrobacter rodentium-associated colonic hyperplasia and Stx-mediated renal injury. Given antibiotic-associated dysbiosis of the gut is associated with inflammation and the emergence of opportunistic pathogens, we examined the effect of Aurodox on the faecal bacteriome. We show that although the microbial community is altered following Aurodox treatment, changes are distinct from those associated with traditional antibiotic therapies.