The role of the Ferric Uptake Regulator (Fur) in regulation of Helicobacter pylori iron uptake.
BACKGROUND
Availability of the essential nutrient iron is thought to vary greatly in the gastric mucosa, and thus the human gastric pathogen Helicobacter pylori requires regulatory responses to these environmental changes. Bacterial iron-responsive regulation is often mediated by Ferric Uptake Regulator (Fur) homologs, and in this study we have determined the role of H. pylori Fur in regulation of H. pylori iron uptake.


METHODS
Wild-type H. pylori and fur mutant derivatives were compared after growth in iron-restricted and iron-replete conditions. Iron-uptake was measured using 55Fe-labeled iron, whereas gene expression was monitored at the transcriptional level using Northern hybridization and lacZ reporter gene fusions.


RESULTS
Iron-uptake and total cellular iron content were approximately five-fold increased in the fur mutant compared with the wild-type strain, which indicated that in the fur mutant iron-uptake is not repressed by excess iron. A comprehensive screening of all H. pylori genes encoding putative iron-uptake proteins indicated that some of these H. pylori genes are constitutively expressed, while others are iron- and Fur-regulated.


CONCLUSIONS
Iron uptake in H. pylori is in part differently regulated compared with other bacteria, since in H. pylori some iron-uptake systems are constitutively expressed. However, other iron uptake systems of H. pylori display the iron- and Fur-mediated repression that is common in bacteria. Taken together, this Fur-mediated modulation of iron-uptake capacity may be a specific adaptation to the conditions in the human stomach, where iron starvation and iron overload can be encountered in relatively short time intervals.
van Vliet
Arnoud H M
AH
Department of Gastroenterology and Hepatology, Erasmus MC, Rotterdam, The Netherlands. vanvliet@mdl.azr.nl
Stoof
Jeroen
J
Vlasblom
Ronald
R
Wainwright
Stuart A
SA
Hughes
Nicola J
NJ
Kelly
David J
DJ
Bereswill
Stefan
S
Bijlsma
Jetta J E
JJ
Hoogenboezem
Theo
T
Vandenbroucke-Grauls
Christina M J E
CM
Kist
Manfred
M
Kuipers
Ernst J
EJ
Kusters
Johannes G
JG
D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D003470:Culture Media; D029968:Escherichia coli Proteins; D015964:Gene Expression Regulation, Bacterial; D016480:Helicobacter pylori / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D007763:Lac Operon; D009154:Mutation; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D003470:Culture Media; D029968:Escherichia coli Proteins; C028589:FecA protein, E coli; C093120:FrpB protein, bacteria; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron