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Manganese Prevents Death From Bacterial Shiga Toxin

Majid Ali, M.D.

One of my regrets in integrative medicine is not knowing how many safe and effective natural remedies there are that I have not been able to test and validate. I lament the loss of countless such therapies that might have been used in past centuries. I also wonder about many such therapies that remain to be discovered. So, I was thrilled to read the report about the value of mineral manganese in preventing the loss of life caused by the nacterial toxin called Shiga. This was reported in an important paper published in Science 20 January 2012 by Mukhopadhyay, and Linstedt* of Carnegie Mellon University, Pittsburgh,

Shiga toxicosis is caused by infections with Shiga–producing bacteria and is responsible for more than a million deaths each year. Shiga–producing bacteria include the Shigella genus and a highly virulent species of E.coli called enterohemorrhagic Escherichia coli (EHEC). There is no satisfactory treatment for it. Treatment with antibiotics further increases the risk of Shiga release and its fatal consequences. So the very notion of a safe mineral that can prevent death in experimental mice indeed is thrilling.

Manganese in Health and Disease

One crucial function of this trace mineral is to protect various cellular populations in the body from excessive and toxic activity of superoxide, an important Dr. Jekyll / Mr. Hyde oxyradical. Its timely neutralization is important in the prevention of toxicity of elemental oxygen. Manganese is crucial in degradation of superoxide. It also serves as a cofactor for a large number of enzymes with diverse functions, including arginase, cholinesterase, phosphoglucomutase, pyruvate carboxylase, mitochondrial superoxide dismutase and several phosphates, peptidases and glycosyltransferases. Not surprisingly in light of such enzyme-supportive functions, manganese is involved with the following:

 

* Glucose and insulin metabolism

* Lipid metabolism

* Cholesterol metabolism

* Pancreatic function and development

* Bone growth and development

* Prevention of sterility

* Protein and nucleic acid metabolism

* Thyroid hormone production

Manganese also plays other important roles in the physiology of the oxygen-evolving complex of photosynthetic plants.

When exposed to very high concentration, manganese can cause neurological injury which is often irreversible.

Manganese in Industrial Uses

Manganese is a mineral chemical element (element symbol, Mn) which is found as a free element in nature as well as in combination with iron and some other minerals. It is commonly used in industrial metal alloy work, especially in stainless steels. The permanganates of alkaline metals act as potent oxidizers.

Manganese Prevents Shiga Toxicity

Shiga trafficks from the cell surface through endosomes, the Golgi apparatus, and the endoplasmic reticulum, where it translocates to the cytosol and inactivates ribosomes. In this route, its direct trafficking from early endosomes to the Golgi bypasses endosomes and lysosomes, and so avoid degradation. This creates the possibility of using small-molecule inhibitors to target this step and allow its degradation and prevent its toxicity.

Of the cellular factors involved in Shiga toxin trafficking, all but one (a factor called GPP130) are found in the cytosol. This suggests that Shiga evolved to escape the degradation by binding to this factor in the lumen of early endosomes. This raises the possibility that other toxins might also "coopt" proteins in the GPP130, and that other similar and simple natural approaches might be applicable to disabling other lethal toxins like Shiga

* Mukhopadhyay S, Linstedt AD. Manganese Blocks Intracellular Trafficking of Shiga Toxin and Protects Against Shiga Toxicosis. Science. 335:332-335 (20 January 2012)

 

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