Role of divalent metals in infectious disease susceptibility and outcome.

BACKGROUND: Divalent metals play important roles in maintaining metabolism and cellular growth of both eukaryotic hosts and invading microbes. Both metal deficiency and overload can result in abnormal cellular function or damage. Given its central role in host-pathogen interactions, subtle alterations of divalent metal homeostasis can occur in the course of infectious diseases which aim, from the host perspective, either to reduce the availability of respective metals to microbes or to use toxic metal accumulation to eliminate pathogens. AIMS: To provide the reader with background information and clinical data on divalent metal homeostasis in host-pathogen interactions, how this affects the course of infectious disease and whether correction of metal disturbances has shown benefit in infections. SOURCES: An in-depth analysis of PubMed articles related to the topic of this review published in English between 1970 and 2016 was performed. CONTENT: From the microbial perspective, divalent metals are essential for growth and pathogenicity and to mount effective protection against antimicrobial host responses, including toxic radical formation. Microbes have evolved multiple strategies to control their access to divalent metals. From the clinical perspective, alterations of divalent metal levels may result in increased or decreased susceptibility to infection and often occur in response to infections. However, keeping in mind the strategies underlying such alterations, for which the term 'nutritional immunity' was coined, the uncritical correction of such divalent metal imbalances may cause harm to patients. This review addresses the role of the divalent metals iron, selenium, zinc, manganese and copper in infectious diseases from a mechanistic and clinical perspective. IMPLICATIONS: We point out areas of research needed to expand our limited knowledge, hoping to improve the clinical management of patients with infections and to identify promising new targets for treatment by modulation of host or microbe divalent metal metabolism.