Several years ago, one of my colleagues died tragically from a laboratory-acquired Yersinia pestis infection. A description of his illness and of postmortem investigations coordinated by the CDC has recently been published (1). My colleague had been working with a strain of Y. pestis that was thought to be non-pathogenic because of a defect in its iron-acquiring ability. Postmortem studies showed that he had markedly elevated serum iron and other indices of iron overload. Genetic testing revealed that he was homozygous for the C282Y hemochromatosis mutation, although he was not aware of having hemochromatosis and had never had any symptoms of this disease. Hemochromatosis is known to increase the risk of infection by other Yersinia species, including Y. enterocolitica and Y. pseudotuberculosis, which are impaired in their ability to acquire iron from infected hosts (2). The CDC report suggested that my colleague’s hemochromatosis-induced iron overload might have increased the virulence of this attenuated Y. pestis strain.
Eugene Weinberg and others have studied the molecular mechanisms of our evolved iron-withholding defenses and have documented the importance of these defenses in protecting us against pathogens (3). The reduced serum iron seen in patients with infectious diseases is now recognized as an adaptation that decreases the virulence of these diseases, and the dangers of giving iron to patients with infections are well known. Unfortunately, however, the other side of this relationship—that even sub-clinical defects in iron withholding, due to hemochromatosis or other causes, can increase susceptibility to infection—is not widely appreciated. A greater awareness and understanding of the clinical relevance of our iron-withholding defenses should lead to improved medical practice.
1. Fatal laboratory-acquired infection with an attenuated Yersinia pestis strain—Chicago, Illinois, 2009. MMWR 60(7), 201–5, 2011.
3. Weinberg ED. Iron availability and infection. Biochim Biophys Acta 1790(7):600–5, 2009.