Evaluating the Protective Effects of Aurodox in a Murine Model of Shiga Toxin-Producing Escherichia coli.
Shiga Toxin-Producing E. coli (STEC) are a group of acute pathogens of the small intestine which is responsible for foodborne outbreaks of bloody diarrhoea. EHEC infections are often associated with high morbidity and mortality rates due to the production of Shiga toxins (Stx) which can initiate Haemolytic Uremic Syndrome (HUS) which is a major cause of acute renal failure in children. In these studies, we investigate the anti-virulence potential of Aurodox - a natural product of Streptomyces goldiniensis. Our previous work has shown that Aurodox downregulates the expression of the T3SS in STEC, inhibiting epithelial cell colonisation in vitro. Here, we use the Citrobacter rodentium DBS770 (Cr Stx2dact) model of STEC infection to demonstrate that Aurodox protects mice against both Citrobacter rodentium-associated colonic hyperplasia and Stx-mediated renal injury. As antibiotic-associated dysbiosis of the gut is associated with inflammation and the emergence of opportunistic pathogens, we also examined the effect of Aurodox on the murine faecal bacteriome. This work has shown that although the microbial community is altered following Aurodox treatment, these changes are distinct from those associated with traditional antibiotic therapies. Our results demonstrate that Aurodox is associated with an increased abundance of probiotic strains such as Bifidobacterium animalis and Akkermansia mucciniphila in both infected and uninfected mice and reverses the reduction in alpha diversity observed in response to  Cr Stx2dact infection. These results indicate Aurodox as a candidate therapeutic for the treatment of STEC infections.