Nutritional immunity: transition metals at the pathogen–host interface

Vertebrates protect against infection through the sequestration of nutrient metals, and bacterial pathogens have evolved sophisticated acquisition strategies to circumvent this host defence. In this Review, Hood and Skaar describe this molecular arms race for nutrients. Transition metals occupy an essential niche in biological systems. Their electrostatic properties stabilize substrates or reaction intermediates in the active sites of enzymes, and their heightened reactivity is harnessed for catalysis. However, this heightened activity also renders transition metals toxic at high concentrations. Bacteria, like all living organisms, must regulate their intracellular levels of these elements to satisfy their physiological needs while avoiding harm. It is therefore not surprising that the host capitalizes on both the essentiality and toxicity of transition metals to defend against bacterial invaders. This Review discusses established and emerging paradigms in nutrient metal homeostasis at the pathogen–host interface.