ENTRY OF SHIGA TOXIN INTO CELLS

The effect of Shiga toxin with mutations in the A fragment has been te sted on cells in order to get more information about the processing of the A fragment during entry into the cytosol. A mutant with a deletio n between the Al and A2 domain in the A fragment is resistant to cleav age by trypsin and is less toxic than wild type toxin on both Vero and A431 cells. The results support the view that processing of the A fra gment is important for the high toxicity of the wild type toxin. A num ber of cell lines are resistant to Shiga toxin although they bind the toxin. However, A431 cells can be sensitized by butyric acid treatment , and transport of Shiga toxin to the Golgi apparatus seems to be requ ired for the intoxication in the sensitized cells. The role of retrogr ade transport through the Golgi apparatus to the endoplasmic reticulum (ER) will be discussed.