Vibrio cholerae is the causative agent of the severe diarrheal disease cholera. V. cholerae thrives within the human host, where it replicates to high numbers, but it also persists within the aquatic environments of ocean and brackish water. To survive within these nutritionally diverse environments, V. cholerae must encode the necessary tools to acquire the essential nutrient iron in all forms it may encounter. A prior study of systems involved in iron transport in V. cholerae revealed the existence of vciB, which, while unable to directly transport iron, stimulates the transport of iron through ferrous (Fe 2ϩ ) iron transport systems. We demonstrate here a role for VciB in V. cholerae in which VciB stimulates the reduction of Fe 3ϩ to Fe 2ϩ , which can be subsequently transported into the cell with the ferrous iron transporter Feo. Iron reduction is independent of functional iron transport but is associated with the electron transport chain. Comparative analysis of VciB orthologs suggests a similar role for other proteins in the VciB family. Our data indicate that VciB is a dimer located in the inner membrane with three transmembrane segments and a large periplasmic loop. Directed mutagenesis of the protein reveals two highly conserved histidine residues required for function. Taken together, our results support a model whereby VciB reduces ferric iron using energy from the electron transport chain.IMPORTANCE Vibrio cholerae is a prolific human pathogen and environmental organism. The acquisition of essential nutrients such as iron is critical for replication, and V. cholerae encodes a number of mechanisms to use iron from diverse environments. Here, we describe the V. cholerae protein VciB that increases the reduction of oxidized ferric iron (Fe 3ϩ ) to the ferrous form (Fe 2ϩ ), thus promoting iron acquisition through ferrous iron transporters. Analysis of VciB orthologs in Burkholderia and Aeromonas spp. suggest that they have a similar activity, allowing a functional assignment for this previously uncharacterized protein family. This study builds upon our understanding of proteins known to mediate iron reduction in bacteria.
KEYWORDS Vibrio cholerae, iron acquisition, iron reductase
Vibrio cholerae is the etiological agent of the severe diarrheal disease cholera. Not only a highly successful human pathogen, V. cholerae also thrives in its environmental reservoirs, ocean and brackish waters, where it associates with various flora and fauna (1). To survive in these diverse environments, V. cholerae uses a vast array of tools to acquire necessary nutrition. Iron is an essential nutrient with roles in respiration (2, 3), nucleotide reduction (4), and oxidative stress tolerance (5). In oxidizing environments, iron can be found in the ferric state (Fe 3ϩ ), which has low solubility and forms insoluble complexes (6), while the more readily soluble ferrous iron (Fe 2ϩ ) predominates in reducing environments. Within the human, iron is tightly complexed to carrier molecules or proteins (7), greatly restrict...