Anti-Human STX2 (N-terminal) Polyclonal antibody

Enterohemorrhagic Escherichia coli (EHEC) are strains of E. coli that express Shiga toxins (Stx) and cause hemorrhagic colitis. In some cases, disease can progress to hemolytic uremic syndrome, a potentially fatal form of kidney disease. Both enteric and renal disease are associated with the expression of stx genes, which are often carried on lysogenic phage. Toxin is expressed following induction and conversion of the phage to lytic growth. The authors previously used a germ-free mouse model to demonstrate that toxin gene expression is enhanced during growth in vivo and that renal disease is dependent on both prophage induction and expression of Stx2. In the current study, the authors document and quantify necrotizing colitis, examine the progression of enteric and renal disease, and determine the role of Stx2, phage genes, and the type 3 secretion system (T3SS) in bacterial colonization and colitis and systemic disease. By 1 day after inoculation, EHEC-monocolonized mice developed colitis, which decreased in severity thereafter. Systemic disease developed subsequently. Infection with EHEC mutant strains revealed that renal failure and splenic necrosis were absolutely dependent on the expression of Stx2 but that T3SS function and prophage excision were not necessary for systemic disease. In contrast, colitis was only partly dependent on Stx2. This study demonstrates that in germ-free mice, like in human patients, EHEC causes early colitis followed by renal failure and that systemic disease but not colitis is Stx2 dependent.

Shiga toxin (Stx) is the key virulent factor in Shiga toxin-producing Escherichia coli (STEC). To date, three Stx1 subtypes and seven Stx2 subtypes have been described in E. coli, which differed in receptor preference and toxin potency. Here, we identified a novel Stx2 subtype designated Stx2h in E. coli strains isolated from wild marmots in the Qinghai-Tibetan plateau, China. Stx2h shares 91.9% nucleic acid sequence identity and 92.9% amino acid identity to the nearest Stx2 subtype. The expression of Stx2h in type strain STEC299 was inducible by mitomycin C, and culture supernatant from STEC299 was cytotoxic to Vero cells. The Stx2h converting prophage was unique in terms of insertion site and genetic composition. Whole genome-based phylo- and patho-genomic analysis revealed STEC299 was closer to other pathotypes of E. coli than STEC, and possesses virulence factors from other pathotypes. Our finding enlarges the pool of Stx2 subtypes and highlights the extraordinary genomic plasticity of E. coli strains. As the emergence of new Shiga toxin genotypes and new Stx-producing pathotypes pose a great threat to the public health, Stx2h should be further included in E. coli molecular typing, and in epidemiological surveillance of E. coli infections.