Escherichia coli O157 interactions with human intestinal Caco-2 cells and the influence of fosfomycin

K. Izumikawa, Y. Hirakata, T. Yamaguchi, H. Takemura, S. Maesaki, K. Tomono, S. Igimi, M. Kaku, Y. Yamada, S. Kohno, S. Kamihira

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18 Citations (Scopus)

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-α), 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-α 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.

Original languageEnglish
Pages (from-to)341-347
Number of pages7
JournalJournal of Antimicrobial Chemotherapy
Volume42
Issue number3
DOIs
Publication statusPublished - 1998 Sep
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Microbiology (medical)
  • Infectious Diseases
  • Pharmacology (medical)

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    Izumikawa, K., Hirakata, Y., Yamaguchi, T., Takemura, H., Maesaki, S., Tomono, K., Igimi, S., Kaku, M., Yamada, Y., Kohno, S., & Kamihira, S. (1998). Escherichia coli O157 interactions with human intestinal Caco-2 cells and the influence of fosfomycin. Journal of Antimicrobial Chemotherapy, 42(3), 341-347. https://doi.org/10.1093/jac/42.3.341