Host response to the Subtilase cytotoxin produced by locus of enterocyte effacement (LEE)-negative Shiga-toxigenic Escherichia coli (STEC).

Shiga-toxigenic Escherichia coli (STEC) is a major bacterium responsible for disease resulting from foodborne infection, including bloody diarrhea and hemolytic uremic syndrome (HUS). STEC produces important virulence factors such as Shiga toxin (Stx) 1 and/or 2. In the STEC family, some Locus for Enterocyte Effacement (LEE)-negative STEC produce two different types of cytotoxins, Stx2 and Subtilase cytotoxin (SubAB). The Stx2 and SubAB cytotoxins are structurally similar and composed of one A subunit and pentamer of B subunits. The catalytically active A subunit of SubAB is a subtilase-like serine protease and specifically cleaves an endoplasmic reticulum (ER) chaperone GRP78/BiP, a monomeric ATPase that is crucial in protein folding and quality control. The B subunit binds to cell surface receptors. SubAB recognizes sialic carbohydrate-modified cell surface proteins as a receptor. After translocation into cells, SubAB is delivered to the ER, where it cleaves GRP78/BiP. SubAB-catalyzed BiP cleavage induces ER stress, which causes various cell events including inhibition of protein synthesis, suppression of nuclear factor-kappa B (NF-κB) activation, apoptotic cell death, and stress granules formation. In this review, we describe SubAB, the SubAB receptor and the mechanism of cell response to the toxin. This article is protected by copyright. All rights reserved.