Shiga toxin is a dangerous by-product of certain infectious bacteria, such as strains of Shigella and E. coli, which causes symptoms ranging from intestinal pain to kidney failure and even death. Over 150 million people are afflicted with Shiga toxicosis every year, mostly in developing countries where waterborne diseases are prevalent. It is estimated that Shiga toxins kill more than one million people annually, and is particularly lethal to children. Even in developed countries, Shiga toxicosis remains a threat via foodborne outbreaks.
While exploring the inner workings of the cell, scientists at Carnegie Mellon discovered that Shiga toxin exploits the GPP130 protein found in the Golgi apparatus. As described in their article for the January 20th issue of Science, when a harmful substance enters the cell, it is normally packaged by the Golgi apparatus and sent to the lysosome for degradation. GPP130, however, is an unusual protein that cycles from the Golgi apparatus to endosomes and back without crossing paths with the lysosome. This feature of the GPP130 is utilized by the Shiga toxin which binds to the protein to avoid detection allowing it to remain in the cell where it can cause harm.
However, when high levels of manganese infiltrate the cell, GPP130 alters its pathway to go directly to the lysosome. Beyond a certain point, manganese is also toxic to humans, but the concentrations and methods of administration are already well-documented.
“Manganese is inexpensive. While Shiga toxin affects people in the developed world, it affects far more people in the developing world. An inexpensive, accessible treatment– not a designer drug — is the ideal solution,” says Adam Linstedt, professor of biological sciences at Carnegie Mellon. “While further testing is needed to determine if manganese is a suitable treatment for humans, I’m optimistic that trials should move forward quickly.
Current treatment methods utilize antibiotics to kill the Shiga-excreting bacteria, which actually causes them to lyse (or break apart) and release the toxin in higher concentrations to the detriment of the host. The researchers propose using manganese in conjunction with the antibiotics to neutralize the toxin as well as the bacteria simultaneously. If the scientists are successful in balancing the manganese dosage and the proper supply chain avenues are set up, millions of lives could be saved.
