2013 Winner: Studies with Helicobacter pylori: Filling in the mystery sequence of the cagY gene and determining w

Project Information
Studies with Helicobacter pylori: Filling in the mystery sequence of the cagY gene and determining w
Physical and Biological Sciences
METX undergraduate research
Helicobacter pylori are human pathogenic bacteria. It is found in the stomach on the gastric mucosa. Its pathogenesis is linked to cancer development and ulcers in the gastric mucosa. The strains that are more likely to cause these more severe pathologies have a cag Pathogenicity Island (cag PAI), which is a region of DNA in their genome that encodes for virulence factors that are related to each other. The cag PAI encodes for a Type IV secretion system, which allows the bacteria to translocate an effector protein into the host cells. For a functional type IV secretion system, it needs a filamentous sheath, CagY, to protect it and to be able to translocate the effector protein, CagA. CagY protects the type IV secretion system against the harsh environment of the stomach and from the host immune system. H. pylori strain SS1 has cagA gene but there is no translocation into the host cells. We use Sanger sequencing to focus on the condition of the cagY gene to determine the cause of this problem. The cagY gene is the last to be sequenced in the SS1 genome, because of the extensive repeated DNA sequences. Our results have added to the SS1 genome.
H. pylori are motile bacteria, meaning it has polar flagella that allow it to swim in the gastric mucosa. It uses a complex signaling pathway, known as chemotaxis to swim in the direction of nutrients or growth factors, chemoattractants, and away from caustic chemicals, chemorepellents. Chemotaxis results in higher colonization rates in the gut mucosa. H. pylori use chemoreceptors to recognize chemoattractants and chemorepellents. H. pylori has four chemoreceptors: TlpA, TlpB, TlpC, and TlpD. A normal host response to invading pathogens is for the host immune system to release reactive oxygen species (ROS) to try and kill the invading cells. ROS are caustic chemicals that are harmful to cells. We are interested in the chemotactic response of H. pylori to hydrogen peroxide, using microscopic visualization. We examined H. pylori mutants each one missing a different chemoreceptor and how it responded to hydrogen peroxide. The findings that include a chemoreceptor mutant that does not respond like wild type SS1 would most likely be the chemoreceptor responsible for hydrogen recognition.
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  • Sarina Porcella (Merrill)