How is regulation of motility and chemotaxis required for pathogenicity in Helicobacter pylori, specifically for toxin delivery of VacA.

• Applicant: Dr. Daniela Keilberg
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2014 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 256527270

Helicobacter pylori causes gastritis and gastric cancer. It was shown that the regulation of motility plays an important role for the pathogenicity. Therefore, it has been suggested that the bacteria attach to the epithelial cells depending on regulated motility and chemotaxis to deliver toxins. An important toxin, VacA, has been studied in detail and it was shown how VacA causes cell death of epithelial cells. In my research project I want to investigate how H. pylori cells find their position at or in the vicinity of epithelial cells to transfer the toxin VacA and why chemotaxis is crucial for that process. To find the relationship between VacA transfer and chemotaxis, I will first analyze whether the pathogenicity, which is caused by chemotaxis, directly dependents on VacA. For this, I examine whether VacA and chemotaxis proteins are within one signalling pathway, and if I can restore the reduced pathogenicity of H. pylori chemotaxis mutants by increased VacA expression. Furthermore, I want to find out whether H. pylori cells must be attached to epithelial cells to transfer the toxin VacA and whether attachment leads to increased toxin production. In addition to the experiments carried out with mice I want to establish a new system, the gastric organoids. Using gastric organoids I would have a highly reproducable system and will be able to minimize animal testing. To get new insights into the function of chemotaxis for pathogenicity, I want to record videos of the infected organoids under a confocal microscope to see when a mutant without chemotaxis behaves different compared to the wild type.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professorin Dr. Karen Ottemann