title: Investigation of encephalopathy caused by Shiga toxin 2c-producing Escherichia coli infection in mice.
abstract: A large outbreak of Shiga toxin (Stx)-producing enteroaggregative Escherichia coli (EAEC) O104:H4 occurred in northern Germany. From this outbreak, at least 900 patients developed hemolytic uremic syndrome (HUS), resulting in more than 50 deaths. Thirty percent of the HUS patients showed encephalopathy. We previously established a mouse model with encephalopathy associated with blood brain barrier (BBB) damage after oral infection with the Shiga toxin (Stx) 2c-producing Escherichia coli O157: H- strain E32511 (E32511). In this model, we detected high expression of the Stx receptor synthase enzyme, glycosphingolipid globotriaosylceramide (Gb3) synthase, in endothelial cells (ECs) and neurons in the reticular formation of the medulla oblongata by in situ hybridization. Caspase-3 was activated in neurons in the reticular formation of the medulla oblongata and the anterior horn of the spinal cord. Astrocytes (ASTs) were activated in the medulla oblongata and spinal cord, and a decrease in aquaporin 4 around the ECs suggested that BBB integrity was compromised directly by Stx2c or through the activation of ASTs. We also report the effectiveness of azithromycin (AZM) in our model. Moreover, AZM strongly inhibited the release of Stx2c from E32511 in vitro.
authors.affiliation: Department of Bacteriology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. yunus09@bact.med.kyushu-u.ac.jp
authors.forename: Muhammad Yunus
authors.initials: MY
authors.lastname: Amran
authors.forename: Jun
authors.initials: J
authors.lastname: Fujii
authors.forename: Satoshi O
authors.initials: SO
authors.lastname: Suzuki
authors.forename: Glynis L
authors.initials: GL
authors.lastname: Kolling
authors.forename: Sharon Y A M
authors.initials: SY
authors.lastname: Villanueva
authors.forename: Mosaburo
authors.initials: M
authors.lastname: Kainuma
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Hideko
authors.initials: H
authors.lastname: Kameyama
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yoshida
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D051401:Aquaporin 4 / Q000378:metabolism; D001253:Astrocytes; D017963:Azithromycin / Q000627:therapeutic use; D001812:Blood-Brain Barrier; D053148:Caspase 3; D042783:Endothelial Cells / Q000201:enzymology; D004927:Escherichia coli Infections / Q000150:complications*; D005260:Female; D008526:Medulla Oblongata / Q000166:cytology; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000201:enzymology; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000209:etiology* / Q000382:microbiology*; D054323:Shiga-Toxigenic Escherichia coli / Q000187:drug effects / Q000472:pathogenicity*
chemical_list: D000900:Anti-Bacterial Agents; D051401:Aquaporin 4; D017963:Azithromycin; D053148:Caspase 3