Roles for multiple iron acquisition systems in Vibrio cholerae

Peng, Eric Dwun Hui
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Vibrio cholerae is a highly successful human pathogen and environmental organism. To thrive in these diverse environments, it must encode the tools necessary to acquire essential nutrients such as iron. A number of V. cholerae iron acquisition systems have been identified, and altogether are necessary for growth; however, the roles of each individual system are poorly understood. To test the roles of individual systems, we generated a series of mutants in which only one of the four systems, Feo, Fbp, Vct, and Vib, that support iron acquisition on unsupplemented LB remains functional. Analyses of these mutants under different growth conditions demonstrate that these systems are not redundant. They are limited by substrate availability; the Fe2+-specific transporter, Feo, fails to stimulate growth in environments which favor Fe3+ and the Fe3+-specific transporter, Fbp, fails to stimulate growth in environments which favor Fe2+. While the Vct system transports high-affinity iron binding compounds, or siderophores, this system also supports robust growth in the presence of ascorbate, suggesting Fe-ascorbate as a potential substrate. A strain defective in all four systems has a severe growth defect in aerobic conditions, but accumulates iron and grows at wild-type levels in the absence of oxygen. These data support the presence of an additional, unidentified iron transporter in V. cholerae which does not share apparent homology to known iron transporters from other organisms. Further, V. cholerae VciB plays a role in iron acquisition by promoting the reduction of Fe3+ to Fe2+. Deletion of the major NADH dehydrogenase, Na+-NQR alters the kinetics of iron reduction; as such, we propose a model whereby VciB mediates reduction of iron by re-directing electrons from the electron transport chain. VciB supports Fe2+ transport through the Feo system, as strains dependent on Feo are stimulated by the presence of vciB. Analyses of VciB orthologs indicate a shared function for a family of proteins of previously uncharacterized function. In total, these studies provide new insights into the functional roles of different V. cholerae systems involved in iron acquisition.