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Mitotic block and delayed lethality in HeLa epithelial cells exposed to Escherichia coli BM2-1 producing cytotoxic necrotizing factor type 1.

Abstract
The cytopathic effect (CPE) of Escherichia coli producing cytotoxic necrotizing factor type 1 (CNF1) was investigated by using a human epithelial cell (HeLa) model of infection with CNF1-producing E. coli BM2-1. This strain was shown to bind loosely, but massively, to HeLa cells. A 4-h interaction between bacteria and eukaryotic cells triggered the delayed appearance of a progressive dose-dependent CPE characterized by (i) intense swelling of cells accompanied by the formation of a dense network of actin stress fibers, (ii) inhibition of cell division due to a complete block in the G2 phase of the cell cycle, and (iii) nucleus swelling and chromatin fragmentation. These alterations resulted in cell death starting about 5 days after interaction. The absence of multinucleation clearly distinguished the CPE from the effect produced by cell-free culture supernatants of infected cells nor prevented by a CNF1-neutralizing antiserum. Pathogenicity was completely abolished after Tn5::phoA insertion mutagenesis in the cnf-1 structural gene but not restored by trans complementation with a recombinant plasmid containing intact cnf-1 and its promoter. These results suggest that a gene downstream of cnf-1, essential to the induction of the CPE, was affected by the mutation. On the other hand, transformation of the wild-type strain BM2-1 with the same recombinant plasmid leads to a significant increase in both CNF1 activity and CPE, demonstrating the direct contribution of CNF1 to the CPE. In conclusion, the pathogenicity of E. coli BM2-1 for HeLa cells results from a complex interaction involving cnf-1 and associated genes and possibly requiring a preliminary step of binding of bacterial organisms to target cells.
AuthorsJ De Rycke, P Mazars, J P Nougayrede, C Tasca, M Boury, F Herault, A Valette, E Oswald
JournalInfection and immunity (Infect Immun) Vol. 64 Issue 5 Pg. 1694-705 (May 1996) ISSN: 0019-9567 [Print] United States
PMID8613380 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Bacterial Toxins
  • Chromatin
  • Cytotoxins
  • DNA Primers
  • DNA, Bacterial
  • Escherichia coli Proteins
  • Hemolysin Proteins
  • cytotoxic necrotizing factor type 1
  • DNA
Topics
  • Bacterial Toxins (biosynthesis, genetics, toxicity)
  • Base Sequence
  • Cell Death (drug effects)
  • Chromatin (drug effects)
  • Cytotoxins (biosynthesis, genetics, toxicity)
  • DNA (metabolism)
  • DNA Damage
  • DNA Primers (genetics)
  • DNA, Bacterial (genetics)
  • Escherichia coli (genetics, pathogenicity, physiology)
  • Escherichia coli Proteins
  • Fimbriae, Bacterial (physiology)
  • Genes, Bacterial
  • HeLa Cells
  • Hemolysin Proteins (toxicity)
  • Humans
  • Mitosis (drug effects)
  • Molecular Sequence Data
  • Virulence (genetics)

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