Nutritional immunity: transition metals at the pathogen–host interface
Top Cited Papers
- 16 July 2012
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Microbiology
- Vol. 10 (8), 525-537
- https://doi.org/10.1038/nrmicro2836
Abstract
Microbial pathogens require nutrient metals in order to grow and cause disease. However, excess metals are toxic, so metal levels must be tightly regulated during infection. Vertebrates have evolved to exploit this metal dependence and metal toxicity through strategies that either prevent access to nutrient metal or direct excess metals towards invading pathogens. Collectively, these processes are known as nutritional immunity. The struggle between host and pathogen for nutrient metals is best studied in the area of Fe. Fe is sequestered from invading pathogens either intracellularly or in high-affinity Fe-binding proteins. To combat host-mediated Fe sequestration, microbial pathogens elaborate several high-affinity Fe acquisition systems. Recently, vertebrate proteins of the innate immune system have been identified that prevent microbial infection through the chelation of nutrient Mn and Zn. These proteins are members of the S100 family of Ca-binding proteins and are abundant at sites of inflammation. In addition to Mn and Zn sequestration, vertebrates can use strategies to direct toxic levels of Mn and Zn towards microbial pathogens. Bacterial measures to combat Mn and Zn sequestration, as well as the toxicity that is associated with excess levels of these metals, are beginning to be uncovered. It is becoming increasingly evident that host-mediated direction of excess Cu towards microbial pathogens is a crucial aspect of vertebrate defence against infection. This observation has provided an explanation for the broad conservation of Cu detoxification systems across disease-causing microorganisms. The importance of nutritional immunity for defence against infection is highlighted by the observation that inherited defects in transition metal homeostasis dramatically affect host susceptibility to certain infectious diseases. This fact underscores the tremendous therapeutic potential of targeting bacterial metal acquisition systems.Keywords
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