Escherichia coli Subtilase Cytotoxin

Subtilase cytotoxin (SubAB) is the prototype of a new AB(5) toxin family produced by a subset of Shiga toxigenic Escherichia coli (STEC) strains. Its A subunit is a subtilase-like serine protease and cytotoxicity for eukaryotic cells is due to a highly specific, single-site cleavage of BiP/GRP78, an essential Hsp70 family chaperone located in the endoplasmic reticulum (ER). This cleavage triggers a severe and unresolved ER stress response, ultimately triggering apoptosis. The B subunit has specificity for glycans terminating in the sialic acid N-glycolylneuraminic acid. Although its actual role in human disease pathogenesis is yet to be established, SubAB is lethal for mice and induces pathological features overlapping those seen in the haemolytic uraemic syndrome, a life-threatening complication of STEC infection. The toxin is also proving to be a useful tool for probing the role of BiP and ER stress in a variety of cellular functions.