Impact of Na-Translocating NADH:Quinone Oxidoreductase on Iron Uptake and Expression in Vibrio Cholerae

The Na ion-translocating NADH:quinone oxidoreductase (NQR) from is a membrane-bound respiratory enzyme which harbors flavins and Fe-S clusters as redox centers. The NQR is the main producer of the sodium motive force (SMF) and drives energy-dissipating processes such as flagellar rotation, substrate uptake, ATP synthesis, and cation-proton antiport. The NQR requires for its maturation, in addition to the six structural genes , a flavin attachment gene, , and the gene, presumably encoding a Fe delivery protein. We here describe growth studies and quantitative real-time PCR for the O395N1 wild-type (wt) strain and its mutant Δ and Δ strains, impaired in respiration. In a comparative proteome analysis, FeoB, the membrane subunit of the uptake system for Fe (Feo), was increased in In this study, the upregulation was confirmed on the mRNA level and resulted in improved growth rates of with Fe as an iron source. We studied the expression of on other respiratory enzyme deletion mutants such as the mutant to determine whether iron transport is specific to the absence of NQR resulting from impaired respiration. We show that the operon comprises, in addition to the structural genes, the downstream and genes on the same operon and demonstrate induction of the operon by iron in wt. In contrast, expression of the gene in is repressed by iron. The lack of functional NQR has a strong impact on iron homeostasis in and demonstrates that central respiratory metabolism is interwoven with iron uptake and regulation. Investigating strategies of iron acquisition, storage, and delivery in is a prerequisite to understand how this pathogen thrives in hostile, iron-limited environments such as the human host. In addition to highlighting the maturation of the respiratory complex NQR, this study points out the influence of NQR on iron metabolism, thereby making it a potential drug target for antibiotics.