Nickel represses the synthesis of the nickel permease NixA of Helicobacter pylori.
Nickel acquisition is necessary for urease activity, a major virulence factor of the human gastric pathogen Helicobacter pylori. NixA was identified as a specific nickel uptake system in this organism. Addition of small amounts of nickel to media strongly stimulates urea hydrolysis. On the other hand, high nickel concentrations are deleterious to cell growth. As a possible protective reaction, nickel uptake seems to be reduced in H. pylori grown in nickel-rich media. These observations led to investigations of regulation of the expression of the nickel permease NixA. We found that increasing the nickel concentration in media reduced the amount of NixA. In order to address the question of whether this phenomenon was subject to transcriptional or translational regulation, we quantified nixA mRNA from H. pylori by real-time PCR. The amount of nixA mRNA was gradually reduced five- to sevenfold in a time- and concentration-dependent manner. Repression could be measured as soon as 5 min after nickel addition, and the maximum repression occurred after 20 to 30 min. The maximum repression was obtained with an external nickel concentration of 100 microM. The observed nickel repression of NixA was dependent on nikR encoding the nickel-responsive regulatory protein NikR. In conclusion, we demonstrated that synthesis of the NixA nickel permease of H. pylori shows nickel-responsive regulation mediated by NikR to maintain the balance between effective nickel acquisition and a toxic overload.
Wolfram
Lutz
L
Department of Internal Medicine, Division of Gastroenterology, University Hospital of Zurich, Raemistr. 100, CH-8091 Zurich, Switzerland.
Haas
Elvira
E
Bauerfeind
Peter
P
D001426:Bacterial Proteins / Q000096:biosynthesis / Q000378:metabolism*; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000096:biosynthesis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D029968:Escherichia coli Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D016480:Helicobacter pylori / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D009532:Nickel / Q000378:metabolism* / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D012329:RNA, Bacterial / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012097:Repressor Proteins / Q000378:metabolism; D013997:Time Factors
D001426:Bacterial Proteins; D027682:Cation Transport Proteins; D029968:Escherichia coli Proteins; C402409:NikR protein, E coli; C095257:NixA protein, Helicobacter pylori; D012329:RNA, Bacterial; D012333:RNA, Messenger; D012097:Repressor Proteins; C022838:nickel chloride; D009532:Nickel