Oxidative stress resistance in Helicobacter pylori
Olczak, Adriana Aneta
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Helicobacter pylori is a gastric pathogen that infects the human gastric mucosa resulting in a number of inflammatory responses including gastritis and peptic ulcer disease. As a pathogen, H. pylori must find a way to overcome the harsh environment within a human stomach. Upon colonization with H. pylori, the host’s phagocytic cells respond, releasing reactive oxygen species (ROS) in an attempt to eradicate the pathogen. Toxic oxygen products encountered by H. pylori must be neutralized by the bacterium in order to maintain a persistent infection. H. pylori is equipped with a number of oxidative stress resistant enzymes and antioxidants. One of those enzymes is the alkyl hydroperoxide reductase (AhpC) which belongs to the family of enzymes catalyzing the reduction of organic peroxides to alcohols. In an attempt to determine its role in oxidative stress, gene disruption mutations in the gene (ahpC) encoding AhpC were isolated. I describe two types of mutants which were obtained. Although both mutants were lacking AhpC protein, the most predominant (type I) mutant synthesized an increased level of another antioxidant protein - NapA (encoding neutrophile activating protein). The second (less common, termed type II) mutant showed wild-type levels of NapA. Both types of mutants were more sensitive to ROS than the wild-type, and they had higher spontaneous mutation freqencies. In all cases, the type II mutant’s phenotype was more severe (more sensitive to stress) than the type I strains. In addition, neither the type I nor type II AhpC mutants were able to colonize mice, indicating AhpC is required for virulence. Two other oxidative stress mutants (napA:cm and double mutant ahpCnapA) were created and differentiated from the wild-type in their sensitivity to oxygen as well as to other oxidative stress generating products. The highest level of sensitivity to oxidative stress imposing factors was observed for the mutant lacking both alkyl hydroperoxide reductase and neutrophile activating protein.