title: Glycosphingolipids are not pivotal receptors for Subtilase cytotoxin in vivo: sensitivity analysis with glycosylation-defective mutant mice.
abstract: Certain glycosphingolipids play important roles as cellular receptor for bacterial toxins with high specificity and strong affinity. In particular AB(5) toxins exhibit typical modes of cell attachment with B5 and invasion and biological effects in cells with A subunit. Subtilase cytotoxin (SubAB) is the prototype of a recently discovered AB(5) cytotoxin family produced by certain strains of Shiga toxigenic Escherichia coli, and shows highly specific serine protease activity toward endoplasmic reticulum chaperone Bip. Since this toxin bound to a mimic of ganglioside GM2, GM2 has been considered to be possible receptor for SubAB. Using six kinds of glycosylation-defective knockout mice lacking certain group of glycosphingolipids, sensitivity to SubAB in vivo was analyzed. Consequently, all mutant mice died at around 70h after intraperitoneal injection of 10 microg (or 7.5 microg) of SubAB as well as wild type mice. These results indicated none of glycolipids are not pivotal receptor for SubAB in the body.
authors.affiliation: Department of Biochemistry II, Nagoya University, Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Aichi, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kondo
authors.forename: Noriyo
authors.initials: N
authors.lastname: Tokuda
authors.forename: Xiayan
authors.initials: X
authors.lastname: Fan
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Yamashita
authors.forename: Koichi
authors.initials: K
authors.lastname: Honke
authors.forename: Hiromu
authors.initials: H
authors.lastname: Takematsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Takematsu
authors.forename: Akira
authors.initials: A
authors.lastname: Togayachi
authors.forename: Michio
authors.initials: M
authors.lastname: Ohta
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kotzusumi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Narimatsu
authors.forename: Orie
authors.initials: O
authors.lastname: Tajima
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Furukaw
authors.forename: Koichi
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D000818:Animals; D029968:Escherichia coli Proteins / Q000378:metabolism / Q000633:toxicity*; D005678:G(M2) Ganglioside / Q000235:genetics / Q000378:metabolism*; D006031:Glycosylation; D051379:Mice; D018345:Mice, Knockout; D018716:Molecular Mimicry; D013381:Subtilisins / Q000378:metabolism / Q000633:toxicity*
chemical_list: D029968:Escherichia coli Proteins; D005678:G(M2) Ganglioside; D013381:Subtilisins; C527234:subtilase cytotoxin, E coli