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Vibrio cholerae , a pandemic diarrheagenic bacterium, is able to synthesize the essential vitamin riboflavin through the riboflavin biosynthetic pathway (RBP) and also to internalize it through the RibN importer. In bacteria, the way riboflavin biosynthesis and uptake functions correlate is unclear. To gain insights into the role of the riboflavin provision pathways in the physiology of  V. cholerae , we analyzed the transcriptomics response to extracellular riboflavin and to deletions of  ribD  (RBP-deficient strain) or  ribN . Many riboflavin-responsive genes were previously reported to belong to the iron regulon, including various iron uptake genes. Real time PCR analysis confirmed this effect and further documented that reciprocally, iron regulates RBP and  ribN  genes in a riboflavin-dependent way. A subset of genes were responding to both  ribD  and  ribN  deletions. However, in the subset of genes specifically affected in the ∆ ribD  strain, the functional terms  protein folding  and  oxidation reduction process  were enriched, as determined by a Gene Ontology analysis. In the gene subset specifically affected in the ∆ ribN  strain, the  cytochrome complex assembly  functional term was enriched. Results suggest that iron and riboflavin interrelate to regulate its respective provision genes and that both common and specific effects of biosynthesized and internalized riboflavin exist.

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Transcriptomics reveals a cross-modulatory effect between riboflavin and iron and outlines responses to riboflavin biosynthesis and uptake in Vibrio cholerae