Escherichia coli Subtilase Cytotoxin: Structure, Function and Role in Disease
Adrienne W. Paton, Hui Wang, Valeria Michelacci, Stefano Morabito and James C. Paton
from: Pathogenic Escherichia coli: Molecular and Cellular Microbiology (Edited by: Stefano Morabito). Caister Academic Press, U.K. (2014)
Subtilase cytotoxin (SubAB) is a recently discovered AB5 toxin family produced by certain strains of pathogenic Escherichia coli, particularly Shiga toxigenic E. coli (STEC) strains that lack the locus of enterocyte effacement (LEE). Its A subunit is a serine protease belonging to the Peptidase_S8 (subtilase) family, while the pentameric B subunit binds to cell surface receptor glycans terminating in the sialic acid N-glycolylneuraminic acid. Receptor binding triggers internalization of the holotoxin and retrograde trafficking to the endoplasmic reticulum (ER), where the A subunit cleaves its only known substrate, the essential Hsp70 family chaperone BiP (GRP78). BiP is a highly conserved master regulator of ER function, which is essential for survival of eukaryotes from simple yeasts to higher organisms such as mammals. Thus, SubAB-mediated BiP cleavage has devastating consequences for the cell, triggering a severe and unresolved ER stress response, ultimately leading to apoptosis. Interestingly, intraperitoneal injection of SubAB is lethal for mice and induces pathological features overlapping those seen in the haemolytic uraemic syndrome, a life-threatening complication of Shiga toxigenic E. coli infection in humans. However, an unequivocal role for SubAB in human disease pathogenesis is yet to be established and carefully designed molecular epidemiological investigations are required to resolve this issue read more ...