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dc.contributor.authorKuhns, Lisa Gail
dc.description.abstractHelicobacter pylori is the etiological agent of peptic ulcer disease, chronic gastritis, and gastric cancer. It is well adapted for a successful life in the harsh environment that it faces and combats acidic gastric conditions with the urease enzyme. Urease functions to neutralize the pH. H. pylori is able to combat oxidative stress due to the function of many antioxidant enzymes such as methionine sulfoxide reductase (Msr) and the thioredoxin (Trx) proteins. Here I explore both Msr and the Trx proteins in more detail and link both to being important for host colonization. I discovered that Msr plays a significant role in nickel-dependent urease maturation. I determined that urease activity in a Δmsr mutant is decreased under elevated oxygen levels. This is not due to urease itself being damaged, as purified urease activity was not decreased upon exposure to oxidants. The nickel levels in the pure urease were decreased due to oxidants, leading to the idea that urease maturation is affected by oxidation. In fact, the urease maturation protein UreG was found to be the oxidizable target and contains an above average methionine content in its primary amino acid sequence. All nine methionines in UreG are susceptible to attack and modification by oxidants, forming the methionine derivative methionine sulfoxide (Met-SO). However, Msr can repair each Met-SO back to the non-oxidized form. The Trx proteins of H. pylori are thought to be involved in the maintenance of the redox balance of the cell. I determined that after deletion of either trx1 or trx2, the macromolecules of the cell are susceptible to damage as a result of oxidant stress. Specific damage to DNA was shown with the formation of 8-oxoguanine in both Δtrx strains, but with a greater amount shown in Δtrx2. There was also a greater abundance of lipid peroxides formed in the Δtrx strains and higher amounts of protein carbonylation in both strains. In addition, a Δtrx1 mutant was decreased in mouse stomach colonization but more interestingly, the Δtrx2 mutant was completely unable to colonize the mouse stomach. My study demonstrates the individual importance of the thioredoxins.
dc.subjectHelicobacter pylori
dc.subjectoxidative stress
dc.subjectmethionine sulfoxide reductase
dc.subjectlipid peroxidation
dc.subjectprotein damage
dc.titleThe roles of methionine sulfoxide reductase and thioredoxin in Helicobacter pylori
dc.description.advisorRobert Maier
dc.description.committeeRobert Maier
dc.description.committeeVincent Starai
dc.description.committeeDuncan Krause
dc.description.committeeTimothy Hoover

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