Secretion and function of putative effector proteins encoded on integrating conjugative elements (ICEs) in Helicobacter pylori

• Applicant: Privatdozent Dr. Wolfgang Fischer
• Subject Area: Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 499103492

The current proposal aims at a comprehensive characterization of the functional roles of putative effector proteins encoded on integrating conjugative elements in H. pylori. Many fundamental aspects of these elements, such as their regulation, are not well-understood, but there is accumulating evidence that ICEs may play an important role in host cell interaction, and thus pathogenesis, of H. pylori. In the proposed project, we intend to elucidate the distribution of ICE cargo genes in the global H. pylori population, the secretion properties of their encoded (putative) effector proteins, and also the functions of these proteins in host cell interaction or interbacterial competition. The first objective is the analysis of the individual ICE cargo gene content in H. pylori strains on a comprehensive global scale. For this objective, we will take advantage of more than 1000 complete genome sequences of H. pylori isolates obtained from more than 50 countries within the Helicobacter pylori genome project (HpGP) initiative (NCI, Rockville, MD, USA). In this unique data set, we will examine ICE cargo gene diversity, and also potential selective pressures on putative effector proteins. A second objective is to generate reporter strains that are suitable for measuring secretion of cargo gene products, and to use these reporters to determine gene expression under different conditions, including target cell contact. As a third and main objective, selected ICE-encoded effector protein candidates will be characterized with respect to their secretion properties, including the determination of secretion signals and the responsible secretion systems, if applicable. This will also involve alternative approaches to identify secreted ICE-encoded proteins. Finally, we will try to evaluate the putative functions of some candidate proteins as host interaction or bacterial competition factors, based on their predicted functional domains.The expected results will contribute to a better understanding of putative ICE-controlled host or bacterial interaction processes in this important pathogen. In this way, they might also help elucidating potential evolutionary benefits of these genetic elements, which do not confer any obvious functions such as antibiotic resistance or metabolic capabilities.

• DFG Programme: Research Grants
• International Connection: USA
• Cooperation Partner: M. Constanza Camargo, Ph.D.