Fur-independent induction of helicobacter pylori flavodoxin-encoding gene (FLDA) under iron starvation

Background and Aims: Helicobacter pylori infection is associated with a variety of diseases including gastric cancer. Flavodoxin is an electron transfer protein containing a flavin mononucleotide prosthetic group and substituted an iron-containing electron transfer protein under iron-limiting conditions. H. pylori flavodoxin has been reported but its pathogenic role is unclear. The aim of this study is to understand a pathogenic role of H. pylori flavodoxin under iron-limiting condition. Methods: The flavodoxin-encoding gene (fldA) was cloned from one of clinical H. pylori isolates (DU17) and its transcript was quantified by primer extension, Northern hybridization, and real-time polymerase chain reaction in different concentrations of an iron chelator. The fldA transcript was also quantified in H. pylori ATCC 700392, lacking a ferric uptake regulatory (fur) protein. Result: Nucleotide sequence of the fldA from H. pylori DU17 revealed a 492-bp (164 amino acids) open reading frame with a deduced amino acid sequence having 97% identity to that from the complete genomic sequence of H. pylori 26695. The deduced promoter [-35, -10, and +1] of the fldA was 56-bp upstream from the first codon of FldA. The fldA transcript (∼0.55-kb) was induced up to 14-fold in both wild-type and fur-knocked-out strains under iron-limiting conditions, suggesting that the fldA induction is independent to the Fur protein. Conclusion: The fldA gene may play an important role in iron starvation conditions.