title: Escherichia coli O157 interactions with human intestinal Caco-2 cells and the influence of fosfomycin.
abstract: It is not clear how Escherichia coli O157 invades human enteric epithelium and causes the haemolytic uraemic syndrome (HUS), and nor has the most appropriate treatment of E. coli O157 infection been established. Verotoxins, leucocytes and proinflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha), interleukin (IL)-6 and IL-8, are considered essential for the development of HUS. We used the Caco-2 cell monolayer system, well-known as an in-vitro model of human intestinal infection, to determine how E. coli O157 interacts with intestinal epithelial cells and also studied the influence of fosfomycin on the virulence of the bacteria. Results showed that the E. coli O157 used in this study did not penetrate the Caco-2 cell monolayer system, unlike Salmonella typhimurium SL1344, and verotoxin 1 (VT 1), but not VT 2, translocated across the system. In an in-vitro conventional assay, fosfomycin increased the amount of verotoxins but it did not influence penetration of bacteria and translocation of verotoxins in the Caco-2 cell monolayer system. The production of both IL-8 (a potent neutrophil activator) and TNF-alpha in the human monocytic THP-1 cell line was reduced by fosfomycin-treated basolateral medium in this system. These results indicate that fosfomycin may be a potent drug for preventing HUS caused by E. coli O157 infection.
authors.affiliation: Department of Laboratory Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Izumikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Hirakata
authors.forename: T
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: H
authors.initials: H
authors.lastname: Takemura
authors.forename: S
authors.initials: S
authors.lastname: Maesaki
authors.forename: K
authors.initials: K
authors.lastname: Tomono
authors.forename: S
authors.initials: S
authors.lastname: Igimi
authors.forename: M
authors.initials: M
authors.lastname: Kaku
authors.forename: Y
authors.initials: Y
authors.lastname: Yamada
authors.forename: S
authors.initials: S
authors.lastname: Kohno
authors.forename: S
authors.initials: S
authors.lastname: Kamihira
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D018938:Caco-2 Cells; D016207:Cytokines / Q000096:biosynthesis; D019453:Escherichia coli O157 / Q000187:drug effects* / Q000378:metabolism; D005578:Fosfomycin / Q000494:pharmacology*; D006463:Hemolytic-Uremic Syndrome / Q000382:microbiology; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D022622:Shiga Toxin 1
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D016207:Cytokines; D022622:Shiga Toxin 1; D005578:Fosfomycin