Trafficking in its natural target cells, including kidney cells. MnCl2 was also reported to protect BALB/c mice from Stx1-S. We did not observe manganese protection from either LY335979 Stx1-S or Stx2a in the outbred CD-1 mouse line. BALB/c mice are null mutants for Slc11a1, an H + /divalent cation antiporter expressed by phagocytes with a high affinity for Mn2+. It is not clear if this genetic mutation could have been a factor in the observed protection against Stx1-S, but outbred CD-1 mice are likely to more closely reflect normal human physiologic responses to Mn2+. In addition, Stx2a, not Stx1-S, is most associated with development of fatal human disease, and the failure to observe protection form Stx2a is significant when considering treatment of human disease. Manganese is an essential trace mineral that is used as a Sodium tauroursodeoxycholate cofactor by enzymes that prevent oxidative stress, to detoxify byproducts of amino acid metabolism in the liver, and function in collagen production. However, manganese overexposure can be toxic, especially to the brain, resulting in permanent neurodegenerative disorders. The most notorious of the conditions caused by manganese overexposure is manganism, the symptoms of which mimic those of Parkinson��s disease. Excess manganese is also implicated in decreased fertility, decreased sperm count and motility, fetal skeletal development manifestations and fetal death, and liver toxicity. The potential for toxicity of the treatment itself raises serious concerns whether manganese can be used to treat STEC infections. The current suggested daily allowances of manganese is 0.14 mg/kg/day, or about 10 mg/day for adults, as determined by the Environmental Protection Agency Reference Dose for Chronic Oral Exposure based on central nervous system effects in adults. The US National Research Council Estimated Safe and Adequate Daily Dietary Intake suggests that 5 mg manganese per day for children and adults 10 years and older is sufficient daily intake. Considering the manganese dose administered to BALB/c mice that conferred protection from Stx1-S, a daily therapeutic dose for an adult weighing approximately 70 kg would be approximately 3,500 mg, 350 times greater than the suggested daily allowance in adults. In summary, currently there are no therapeutics for Stxmediated toxicity, and our studies suggest manganese holds little promise as a therapeutic candidate. Since February, 2013, a previously unrecognized novel avianorigin influenza A virus associated wi