Nickel Homeostasis in Helicobacter Species
Year: 2011
Type: dissertation
Abstract: Gastric Helicobacter species are adapted to colonize the acidic environment of the stomach.\\nColonization with H pylori is life long if untreated, and can lead to gastritis, peptic ulcer\\ndisease and eventually to gastric cancer. Although H pylori is sensitive to many antibiotics in\\nvitro, only a limited number of antibiotics can be used in vivo while increasing resistance\\nagainst these therapeutics significantly impairs the treatment of H pylori infection.\\nMetals play an essential role in the metabolism of all living organisms, including gastric\\nHelicobacter species, but can also be deleterious when metal availability is either too low or\\ntoo high. Therefore cells need to maintain homeostasis of intracellular metal concentrations to\\nallow survival and growth. A better understanding of metal homeostasis in gastric\\nHelicobacter species may allow for the knowledge-led development of therapeutics which are\\nbased on disturbing the balance of the intracellular metal concentrations to either toxicity or\\nrestriction. The focus of this PhD-thesis is on nickel metabolism, since this metal is the\\ncofactor of the urease enzyme and hydrogenase enzyme, both essential for colonization of\\ngastric Helicobacter species. The high expression level of the urease enzyme mediates acid\\nresistance in the presence of urea, but also necessitates the import of relatively high\\nconcentrations of nickel. Although transcriptional regulation by the nickel-dependent\\nregulator NikR has been studied, relative little is known about which proteins are involved in\\nactual transport of nickel. The genome era has opened the possibility of functional genomics\\ninvestigations, using the information from the genomes of different Helicobacter species.\\nMany of the genes of Helicobacter species do not yet have a predicted function, or have been\\nassigned a putative function only based on homology with genes from other bacterial species.\\nComparison of the genomic content of different Helicobacter species and transcriptional and\\nfunctional characterization of the genes putatively involved in nickel homeostasis, as\\npresented in this thesis, will provide more insight in how these bacteria are able to acquire\\nsufficient concentrations of nickel.
Author: Jeroen Stoof
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2144050390