CagA, a protein produced by the bacterium Helicobacter pylori, can alter the population of microbes living in the fruit fly gut, leading to disease symptoms, according to new research published in PLOS Pathogens by Tiffani Jones and Karen Guillemin of the University of Oregon.
Microbes living in the human gut normally help keep people healthy, but disruptions to this microbial community can promote disease. Infections with specific microbial species can disrupt the gut microbiome, but it is unclear how such disruption occurs and whether it promotes disease.
In the new study, Jones and her colleagues used Drosophila fruit flies to test the effects of infection with H. pylori, which can cause gastric cancer in humans. They hypothesized that a protein associated with H. pylori called CagA disrupts the fruit fly gut microbiome and contributes to disease.
To test their hypothesis, the researchers genetically engineered fruit flies to express the CagA protein in their intestines, without being infected by H. pylori. This allowed them to disentangle the specific effects of CagA from the overall effects of H. pylori infection.
They found that CagA expression in the fruit fly gut caused excess growth of intestinal cells and promoted immune system responses that are associated with H. pylori infection. However, these symptoms did not occur in CagA-expressing flies that were raised without microbes, suggesting the importance of the gut microbiome.
Indeed, further investigation revealed that CagA expression was associated with a disrupted gut microbiome in the flies. Exposure to the CagA-expressing flies caused the same microbiome disruptions in normal flies, which was sufficient to cause the same symptoms of excess cell growth and immune response seen in the genetically altered flies.
Overall, these findings show that CagA can indirectly cause disease symptoms by altering the gut microbiome. This raises the possibility that the harmful effects of infection with H. pylori -- and other microbes that may function similarly--could be mitigated by manipulating the balance of microbes in the gut.
"Our work demonstrates for the first time that a bacterial virulence factor like CagA can alter commensal microbial communities to cause disease," the author explain. "This work also reveals that commensal microbial communities may participate in the progression of H. pylori mediated gastric cancer."
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Citation: Jones TA, Hernandez DZ, Wong ZC, Wandler AM, Guillemin K (2017) The bacterial virulence factor CagA induces microbial dysbiosis that contributes to excessive epithelial cell proliferation in the Drosophila gut. PLoS Pathog 13(10): e1006631. https:/
Funding: Research reported in this publication was supported by the National Cancer Institute and the National Institute of General Medical Sciences of the National Institutes of Health under award numbers 1R01CA176579 and 1P50GM098911. Tiffani A. Jones, PhD was supported by a Postdoctoral Fellowship, PF-14-200-01-MPC from the American Cancer Society and Friends of Rob Kinas. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: The authors have declared that no competing interest exist.