Manganese Blocks Intracellular Trafficking of Shiga Toxin and Protects Against Shiga Toxicosis

Abstract

Shunning Shiga Infection with bacteria harboring Shiga toxin is responsible for more than 1 million deaths annually worldwide. Antidotes for the toxin are not available, and treatment with antibiotics is contraindicated because it increases the risk of toxin release (from dead bacteria) and leads to severe forms of the disease. Manganese is an essential nutrient and its toxicology in humans is well studied; it inhibits the normal trafficking of Shiga toxin in tissue culture cells. Mukhopadhyay and Linstedt (p. 332 ) found that levels of Mn 2+ that caused no deleterious effects to normal cellular processes nevertheless altered intracellular trafficking of Shiga toxin so that it was degraded in lysosomes. This conferred very high levels of protection of cultured cells against toxin-induced death and made mice completely resistant to Shiga toxin–induced paralysis and death.