Metal Homeostasis: Regulation of Manganese and Iron in the Rhizobia and Related α‐Proteobacteria

Abstract

Iron is required for many cellular processes, but can be toxic at high concentrations. Thus, iron homeostasis is strictly regulated so that iron acquisition, storage, and consumption are geared to iron availability, and that intracellular levels of free iron do not reach toxic levels. Recently, the roles of manganese and its control in cells have been investigated, and it is becoming clear that some aspects of the metabolism of iron and manganese are interrelated. Manganese is best understood in its role in oxidative stress responses, and the pro‐oxidative effects of intracellular iron functionally link these two metals. Iron and manganese appear to have complementary or compensatory functions as well. In bacteria, it may not be universally true that manganese is an essential nutrient under nonstressed conditions, underscoring a gap in our knowledge of the role of this metal in prokaryotes. Studies of Bradyrhizobium japonicum and other rhizobia reveal that control of iron‐responsive gene expression is fundamentally different in these bacteria when compared with model organisms such as Escherichia coli and Bacillus subtilis . Moreover, the Fur regulatory protein that dominates iron‐responsive gene expression in those model systems has been co‐opted to respond to manganese in the rhizobia. Finally, it appears that mechanisms of iron‐ and manganese‐responsive gene expression in the rhizobia are paradigmatic for the α‐proteobacteria. This is remarkable because the α‐proteobacteria are metabolically and ecologically diverse, making it difficult to correlate their unique metalloregulation with specific adaptations.