Ionic requirements for entry of Shiga toxin from Shigella dysenteriae 1 into cells

Infection and Immunity
|February 1, 1987
PubMed

Insights

Shiga toxin entry into cells requires specific divalent cations, particularly calcium (Ca2+), and is influenced by anion type. Cell sensitivity to Shiga toxin varies based on these ionic conditions.

Area of Science:

  • Cell Biology
  • Toxicology
  • Molecular Biology

Background:

  • Shiga toxin is a potent bacterial toxin responsible for severe gastrointestinal and systemic illness.
  • Understanding the cellular entry mechanisms of Shiga toxin is crucial for developing effective countermeasures.

Purpose of the Study:

  • To elucidate the specific ionic requirements for Shiga toxin entry into various cell lines.
  • To investigate the role of divalent cations and anions in modulating cellular sensitivity to Shiga toxin.

Main Methods:

  • Protein synthesis inhibition assays were used to measure Shiga toxin activity.
  • Experiments involved short-term incubations of different cell lines (Vero, HeLa, HEp-2) with Shiga toxin under varying ionic conditions.
  • The effects of divalent cations (CaCl2, SrCl2, MgCl2, BaCl2, CoCl2, MnCl2), calcium transport inhibitors, ionophores, potassium concentrations, and anion substitutions (SO42-, SCN-) were assessed.

Main Results:

  • Cellular sensitivity to Shiga toxin was highly dependent on the presence and type of divalent cations.
  • Vero cells showed highest sensitivity with CaCl2 and SrCl2, while HeLa cells were sensitive to MgCl2, SrCl2, and CaCl2.
  • Certain cations (BaCl2, CoCl2, MnCl2) and calcium transport inhibitors protected cells, suggesting Ca2+ influx is critical.
  • Anion composition and potassium levels also influenced Shiga toxin sensitivity.
  • Shiga toxin binding to cells occurred at acidic pH, but this was not affected by altering intracellular vesicle pH.

Conclusions:

  • Calcium (Ca2+) transport through cellular channels is a necessary step for Shiga toxin entry.
  • The specific anions present in the cellular environment significantly impact cell susceptibility to Shiga toxin.
  • These findings provide insights into the molecular mechanisms of Shiga toxin pathogenesis and potential therapeutic targets.

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