Helicobacter injects its toxin into host cell

Helicobacter pylori is known to infect the mucus layer and cells forming the inner lining of the stomach, thereby causing gastric inflammation. Now the molecular structure of the bacterium’s major pathogenicity factor (CagA toxin) has been published in PNAS by a group of researchers including Rainer Haas and his team at the LMU.

The virulence of the most pathogenic strains of Helicobacter pylori is caused by a Type IV secretion system encoded by the set of cag genes. The bacterium uses the system to inject the toxic protein CagA into the host cells much like a syringe, and the toxin then disrupts intracellular signaling pathways and promotes tumor development.

By solving the structure of CagA and investigating mechanistic details of the Cag system the researchers found novel structural features in the spatial conformation of CagA. For the toxin to be injected into the target cell, CagA needs to bind to an integrin receptor on the cell surface. A special protein fold was identified that binds to the integrin receptor. Due to the unique spatial structure of the toxin, a 100 amino acid peptide taken from the CagA binding region could specifically and effectively block the injection mechanism into cultured gastric cells.

The team around Rainer Haas will now work on a detailed understanding of the injection process on the molecular level with the long-term goal of completely blocking entry of the toxin protein.

For the more detailed original news item see "The delivery of a bacterial oncoprotein” in the LMU press release archive. The study was published in the Proceedings of the National Academy of Sciences of the USA (PNAS 109(36):14640-14645).