Renal damage and death in weaned mice after oral infection with Shiga toxin 2-producing Escherichia coli strains

Abstract

SummaryEnterohaemorrhagic Escherichia coli (EHEC) O157:H7 infections are considered a public health problem in both developed and developing countries because of their increasing incidence and the severity of clinical presentation. Approximately 10% of infected patients develop complications such as haemolytic uraemic syndrome (HUS) characterized by acute renal failure, thrombocytopenia and haemolytic anaemia. The precise sequence of events leading to HUS is still understood incompletely. Because of the lack of a reproducible small animal model for EHEC infections, in vivo studies examining EHEC-host early interactions are limited and insufficient. The aim of this study was to characterize the weaned BALB/c mouse as a model of E. coli O157:H7 infection. In this paper we report that human Shiga toxin 2 (Stx2)-producing EHEC strains can adhere to the intestinal epithelium of weaned BALB/c mice, and produce local damage which leads to systemic disease and death in a percentage of infected mice. The lethality of the EHEC strain is closely age-dependent, and is related to the bacterial ability to colonize intestine and to produce Stx2. It can be concluded that the weaned BALB/c mouse can be used as a small animal model to study host early responses, and the role of bacterial pathogenic factors in the induction of systemic disease, thus providing a useful tool for the evaluation of therapeutic or vaccine approaches.

Retinoid Levels Influence Enterohemorrhagic Escherichia coli Infection and Shiga Toxin 2 Susceptibility in Mice

“…We have previously shown that EHEC infection of weaned BALB/c mice can be lethal, as a consequence of systemic damage related to Stx2 toxicity (39). In addition, we have also demonstrated that renal dysfunction secondary to EHEC infection is blocked when anti-Stx2-polyclonal serum is simultaneously inoculated, confirming that Stx is responsible for renal damage and an increased plasma urea concentration (43).…”

“…The strain belonged to seropathotype A, according to the classification of Karmali et al (38). The origin, toxin type, eae variant, EHEC Hly production, and 50% cytotoxic dose in a Vero cell assay of this EHEC strain were previously characterized by Fernández-Brando et al (39).…”

Role of bacteriophages in STEC infections: new implications for the design of prophylactic and treatment approaches

“…In order to evaluate the in vivo effect of chitosan during the infection process, mice were orally challenged with a wild-type EDL933W strain, based on the model described by Brando and collaborators 9 . Another mouse group was also treated with chitosan, administered orally 2 hours post-infection, and survival was followed for one week.…”

Immunization with a Chimera Consisting of the B Subunit of Shiga Toxin Type 2 and Brucella Lumazine Synthase Confers Total Protection against Shiga Toxins in Mice

“…The weaned mouse model is an effective and reliable animal model for studying the pathology of EHEC infection (34,43). We demonstrated that weaned mice infected with Stx2-producing E. coli O157:H7 strains, isolated from HUS patients, experience renal dysfunction and death during the 3 d postinfection.…”

“…The enterohemorrhagic Stx2-producing E. coli O157:H7 (EHEC) was isolated from a fecal specimen of a child with HUS and was characterized by Brando et al (34). Bacterial cultures were performed as previously described (34). Briefly, strains were cultured overnight at 37˚C in Tryptic Soy Broth (TSB) (Difco, Le Point de Claix, France).…”