Manganese May Treat Shigellosis

A simple dose of inexpensive manganese chloride may be the first effective treatment for shigellosis, a food- and waterborne gastrointestinal illness that each year kills more than 1 million people, particularly those in developing countries (Science, DOI: 10.1126/science.1215930). The disease is caused by the Shiga toxin, which is produced by the bacteria Shigella and some Escherichia coli strains. There is no effective treatment because as antibiotics destroy bacteria they spill more toxin into the body, worsening the illness. But Adam D. Linstedt and Somshuvra Mukhopadhyay of Carnegie Mellon University performed tests in cell cultures and on mice showing that manganese thwarts the toxin’s ability to kill cells. Normally, the Shiga toxin remains inside a cell by hitching itself to the protein GPP130. This protein moves back and forth between various cell structures, avoiding molecule-digesting structures known as lysosomes. When manganese enters a cell, however, it diverts GPP130 to lysosomes by an unknown mechanism. With no GPP130 available for binding, the Shiga toxin itself can’t avoid the lysosomes and is destroyed. The researchers found that a nontoxic dose of manganese protected 100% of mice given high doses of Shiga toxin. They also hypothesize that because manganese renders the toxin nontoxic, its use in conjunction with antibiotics could be an even more powerful therapy.