Transcriptional profiling of Helicobacter pylori Fur- and iron-regulated gene expression.
Intracellular iron homeostasis is a necessity for almost all living organisms, since both iron restriction and iron overload can result in cell death. The ferric uptake regulator protein, Fur, controls iron homeostasis in most Gram-negative bacteria. In the human gastric pathogen Helicobacter pylori, Fur is thought to have acquired extra functions to compensate for the relative paucity of regulatory genes. To identify H. pylori genes regulated by iron and Fur, we used DNA array-based transcriptional profiling with RNA isolated from H. pylori 26695 wild-type and fur mutant cells grown in iron-restricted and iron-replete conditions. Sixteen genes encoding proteins involved in metal metabolism, nitrogen metabolism, motility, cell wall synthesis and cofactor synthesis displayed iron-dependent Fur-repressed expression. Conversely, 16 genes encoding proteins involved in iron storage, respiration, energy metabolism, chemotaxis, and oxygen scavenging displayed iron-induced Fur-dependent expression. Several Fur-regulated genes have been previously shown to be essential for acid resistance or gastric colonization in animal models, such as those encoding the hydrogenase and superoxide dismutase enzymes. Overall, there was a partial overlap between the sets of genes regulated by Fur and those previously identified as growth-phase, iron or acid regulated. Regulatory patterns were confirmed for five selected genes using Northern hybridization. In conclusion, H. pylori Fur is a versatile regulator involved in many pathways essential for gastric colonization. These findings further delineate the central role of Fur in regulating the unique capacity of H. pylori to colonize the human stomach.
Ernst
Florian D
FD
Institut für Mikrobiologie und Molekularbiologie, Ernst-Moritz-Arndt-Universität Greifswald, D-17487 Greifswald, Germany.|Department of Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Hospital of Freiburg, D-79140 Freiburg, Germany.|Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, Dijkzigt L-455, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Bereswill
Stefan
S
Department of Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Hospital of Freiburg, D-79140 Freiburg, Germany.
Waidner
Barbara
B
Department of Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Hospital of Freiburg, D-79140 Freiburg, Germany.
Stoof
Jeroen
J
Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, Dijkzigt L-455, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Mäder
Ulrike
U
Institut für Mikrobiologie und Molekularbiologie, Ernst-Moritz-Arndt-Universität Greifswald, D-17487 Greifswald, Germany.
Kusters
Johannes G
JG
Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, Dijkzigt L-455, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Kuipers
Ernst J
EJ
Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, Dijkzigt L-455, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Kist
Manfred
M
Department of Microbiology and Hygiene, Institute of Medical Microbiology and Hygiene, University Hospital of Freiburg, D-79140 Freiburg, Germany.
van Vliet
Arnoud H M
AHM
Department of Gastroenterology and Hepatology, Erasmus MC - University Medical Center Rotterdam, Dijkzigt L-455, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands.
Homuth
Georg
G
Institut für Mikrobiologie und Molekularbiologie, Ernst-Moritz-Arndt-Universität Greifswald, D-17487 Greifswald, Germany.
D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D016480:Helicobacter pylori / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D020543:Proteome; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic
D001426:Bacterial Proteins; D020543:Proteome; D012097:Repressor Proteins; C068477:ferric uptake regulating proteins, bacterial; D007501:Iron