UO's Guillemin develops a fruit fly model for studying infectious diseases

Jim Barlow's Sci-Blog

University of Oregon researcher Karen Guillemin is the corresponding author of a paper appearing in the May 16 issue of the journal PLoS (Public Library of Science) Pathogens. The paper is not likely to make a splash of media coverage, but for molecular biologists it is a significant step forward in the study of a bacterium that causes stomach cancer, gastritis and peptic ulcers.

Guillemin teamed with former doctoral student Crystal M. Botham, now in the department of pediatrics at Stanford University, and current doctoral student Anica M. Wandler developed a transgenic Drosophila model to test how a toxin protein from the bacterium Helicobacter pylori (H. pylori) works in a real animal model. The result is a very versatile and adaptable model for such studies.

Guillemin says that researchers can now use Drosophila (a fruit fly) to "investigate the host pathways manipulated by this bacterial toxin." H. pylori, the authors note, infects the stomachs of at least half of the world's population, and under certain conditions can lead to chronic infections and subsequently disease states.

"In principle," she adds, "this approach could be used to investigate any bacterial toxin" that has lacked having a small animal model to use in studying the infection pathways.

The new research builds upon and confirms earlier work done in tissue cultures that showed that a protein of H. pylori known as CagA is transferred into host tissue cells, where it turns on a receptor pathway whose over-activation creates a major risk for disease development. In essence, Guillemin and team report, CagA mimics a naturally occurring adapter protein to ramp up an important signaling pathway.

In their fruit fly model, the genetic makeup of the flies was altered to see if CagA could mimic the job of Gab proteins, a family of docking molecules involved in multiple signaling pathways mediated by receptor tyrosine kinases. Mutant flies lacking Gab had been previously shown to have a spectrum of defects including abnormal eye development.

In this study, the authors showed that all of defects associated with loss of Gab could be corrected by expressing the H. pylori CagA protein in its place, demonstrating that CagA performs the same function as Gab. Such molecular mimicry, where a toxin protein of a pathogen can carry out the job of a normal cellular protein, is emerging as a common theme in infectious disease.

The article is available for free viewing at the PLoS Pathogens Web site. Click here to go to the article.

For more information, contact me. I'll be glad to pass along Guillemin's contact information.