Year: 2005
Type: dissertation
Abstract: Up to 50 % of the world's population is infected with Helicobacter pylori. Colonization of \nthe mucus layer of the human stomach by H. pylori, is lifelong unless treated with antibiotics \n(26). H. pylori, which is a neutralophilic bacterium, survives in the mucus layer of the human \nstomach with the help of the enzyme urease. Urease is an enzyme that converts urea into \nammonium and carbon dioxide, thereby keeping the intracellular and periplasmic pH at \nneutral. It is estimated that up to 10% of the whole cell protein consists of this nickelcofactored \nenzyme (19). The nickel necessary to activate the urease is thought to come from \nfoodsources, such as nuts, tea and cereals, which are rich in nickel (1). \n\nMetal ions like nickel or iron can be dangerous for bacteria, as they can react with oxygen \nin order to create reactive oxygen species that in turn can destroy macromolecules like \nnucleic acids, proteins and cell wall components (27). Therefore, the bacterial metal \nmetabolism has to be tightly regulated. In H. pylori, regulatory proteins are scarce. Only two \nmetal-regulatory proteins are known, the ferric uptake regulator Fur (4), and the nickel \nresponsive regulator NikR (31). Fur is a regulatory protein that can sense and bind \nintracellular ferrous ions, and subsequently displays iron-dependent binding to conserved \npromoter sequences (Fur boxes) of its target genes (17). The classical regulation is repression \nof iron uptake genes in iron-replete conditions (15, 17, 33). Unlike all other Fur homologs \nknown so far, H. pylori Fur can also bind to Fur-boxes in an iron free form (apo-Fur), as was \nshown for pfr (16) and sodB (Chapter 3). \n\nThe second metal-dependent regulatory protein is NikR, the nickel responsive regulator, \nwhich belongs to the family of Ribbon-Helix-Helix regulatory proteins (9). NikR is directly \ninvolved in the regulation of acid resistance via urease and nickel-uptake (Chapter 4), and \nwas previously demonstrated to mediate regulation of the ferric uptake regulator Fur (7, 12, \n29). \n\nThe aim of this thesis was to gain further insight into the transcriptional regulation the \nferric uptake regulator Fur and the nickel responsive regulator NikR.
Author: Florian Ernst
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1738063858