EHEC is closely linked to a variety of diseases that occur in children, such as diarrhea, fever, bloody diarrhea and hemolytic uremic syndrome (HUS). Humans have been shown to be a reservoir of EHEC O104:H4. Sprouted seeds as well as contaminated vegetables are vital means of spreading the strain. In general, patients infected with EHEC O104:H4 develop symptoms after an incubation period of 8 days. Fortunately, EHEC-associated diseases are self-limiting and most patients resolve spontaneously. A lot of data showed that the proportion of HUS cases was higher than the HUS rate in other strains outbreaks, revealing that EHEC O104:H4 is abnormally virulent.
Fig.1 Hybrid characteristics of E. coli O104:H4 outbreak strain. (Navarro-Garcia, 2015)
Pathogenic Mechanism
Animal experiments play a crucial role in the study of the pathogenesis of EHEC O104:H4 in vivo. Infection of germ-free mice with a specific bacterial strain induced the occurrence of acute tubular necrosis (ATN). This kidney damage is primarily attributed to the production of Shiga toxin 2 (Stx2). Furthermore, another study of this strain and an Stx-negative variant revealed that the 2011 outbreak strain caused weight loss and death in ampicillin-treated mice and that Stx2 was a key virulence factor responsible for the observed pathogenesis. Notably, similar observations were made in two rabbit models, showing a potential link between Stx2 production by EHEC O104:H4 and disease progression.
Treatment
In general, antibiotic therapy is not indicated for EHEC infection because of no benefit or even harm, especially in patients who received antibiotic therapy at the initial stage of diarrhea. A possible mechanism for antibiotics to increase the risk of HUS development in patients is that antibiotics increase Stx production and release. However, different classes of antibiotics have different effects on Stx production in vitro, and the effects are also closely related to the concentration of antibiotics and the nature of EHEC strains.
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- Navarro-Garcia, F. Escherichia coli O104: H4 pathogenesis: an enteroaggregative E. coli/Shiga toxin-producing E. coli explosive cocktail of high virulence. Enterohemorrhagic Escherichia coli and Other Shiga Toxin-Producing E. coli. 2015: 503-529.