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Carnegie Mellon study reveals potential of manganese in neutralizing deadly Shiga toxin
Date:1/19/2012

toxicologist at the University of California, Santa Cruz, who was studying manganese toxicity, noticed that GPP130 was sensitive to manganese. He called Linstedt who began to do a series of experiments on how manganese affects GPP130. Around this time Mukhopadhyay joined Linstedt's lab for his post-doctoral training. He quickly discovered that as concentrations of manganese rise inside the cell, GPP130 changes its pathway and goes directly to the lysosome where it is degraded.

Because Shiga toxin was dependent on GPP130 and manganese caused loss of GPP130, Linstedt and Mukhopadhyay decided to see whether manganese would protect against Shiga toxin infection. In cell cultures, manganese treatment yielded an almost 4,000-fold increase in the amount of Shiga toxin required to induce cell death. In a mouse model, mice exposed to a high dose of Shiga toxin and treated with non-toxic doses of manganese were 100 percent resistant to the toxin.

By introducing manganese, Linstedt and Mukhopadhyay were able to remove Shiga toxin's vehicle for avoiding degradation GPP130. The researchers feel that this could be a promising treatment for neutralizing the effects of Shiga toxin in humans.

"Manganese is inexpensive. While Shiga toxin infection 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," Linstedt said. "We know the toxicity levels of manganese in humans; we know ways to administer it. While further testing is needed to determine if manganese is a suitable treatment for humans, I'm optimistic that trials should move forward quickly."

The researchers also believe that manganese might be able to be used in conjunction with antibiotics. Currently, if an infected person is given an antibiotic, the antibiotic kills the bacteria (E. coli or Shigella) that produce the toxin. This releases the toxin in larger amounts and cau
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Contact: Jocelyn Duffy
jhduffy@andrew.cmu.edu
412-268-9982
Carnegie Mellon University
Source:Eurekalert  

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Carnegie Mellon study reveals potential of manganese in neutralizing deadly Shiga toxin
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