title: Differential regulation of riboflavin supply genes inVibrio cholerae.
abstract: BACKGROUND
  Riboflavin is the precursor of important redox cofactors such as flavin mononucleotide (FMN) and flavin adenine dinucleotide, required for several biological processes.Vibrio cholerae, a pathogenic bacterium responsible for the cholera disease, possesses the ability to biosynthesize de novo as well as to uptake riboflavin through the riboflavin biosynthetic pathway (RBP) and the RibN importer, respectively. The intra-organism relationship between riboflavin biosynthesis and uptake functions has not been studied.
  
  
  RESULTS
  This work determined the transcriptional organization of RBP genes andribNinV. choleraethrough reverse transcription polymerase chain reaction and analyzed their expression when growing with or without extracellular riboflavin using real time PCR. The RBP is organized in three transcriptional units, the major one containingribD, ribE, ribAandribHtogether with genes involved in functions not directly related to riboflavin biosynthesis such asnrdRandnusB. In addition, two independent monocistronic units containribA2andribB, the later conserving a putative FMN riboswitch. TheribNgene is encoded in operon with a gene coding for a predicted outer membrane protein and a gene encoding a protein with a glutaredoxin domain. Regulation analysis showed that among these transcriptional units, onlyribBis negatively regulated by riboflavin and that its repression depends on the RibN riboflavin importer. Moreover, external riboflavin highly inducedribBtranscription in aΔribNstrain. Also, a genomic database search found a negative correlation between the presence ofnrdRandnusBand the FMN riboswitch in bacterial RBP operons.
  
  
  CONCLUSIONS
  Growing in the presence of riboflavin downregulates only a single element among the transcriptional units of riboflavin supply pathways. Thus, endogenous riboflavin biosynthesis seems to be negatively regulated by extracellular riboflavin through its specific effect on transcription ofribBinV. cholerae.
authors.affiliation: Escuela de Biotecnología, Universidad Mayor, Campus Huechuraba, Santiago, Chile.|Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina Norte, Universidad de Chile, Pabellón L. Independencia, 1027, 8380453 Santiago, Chile.
authors.forename: Ignacio Sepúlveda
authors.initials: IS
authors.lastname: Cisternas
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina Norte, Universidad de Chile, Pabellón L. Independencia, 1027, 8380453 Santiago, Chile.
authors.forename: Alexia
authors.initials: A
authors.lastname: Torres
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina Norte, Universidad de Chile, Pabellón L. Independencia, 1027, 8380453 Santiago, Chile.
authors.forename: Andrés Fuentes
authors.initials: AF
authors.lastname: Flores
authors.affiliation: Programa de Microbiología y Micología, Instituto de Ciencias Biomédicas, Facultad de Medicina Norte, Universidad de Chile, Pabellón L. Independencia, 1027, 8380453 Santiago, Chile.
authors.forename: Víctor Antonio García
authors.initials: VAG
authors.lastname: Angulo
keywords: Biosynthesis; Gene regulation; Riboflavin; Transporter; Vibrio cholerae