Fruit flies show how salmonella escapes immune defenses

Researchers have come closer to understanding how these bacteria manage to thwart two major categories of immune defenses at once and set up shop in a host organism. New results are reported in the April 2008 issue of the journal Cell Host & Microbe.

The Emory University research team used a transgenic fruit fly (drosophila) model to test a group of “effector proteins,” also known as “virulence factors,” secreted by invading organisms to usurp the host immune response for their own benefit.

They found that one of these proteins, named AvrA, not only shuts down the key immune signaling pathways JNK and NF-kB, but also turns off the fail safe system organisms have evolved to respond to irreversible threats. This ultimate immune defense, called apoptosis, eliminates invaders along with the infected cells through a system of programmed cell death.

In previous research, the scientists had showed that AvrA could suppress some aspects of immune system signaling in cell culture, but they wanted to study the protein in a whole animal system.

“Bacterial proteins are notoriously difficult to study,” says Andrew Neish, MD, Emory professor of pathology and laboratory medicine and the study's lead scientist. “Using the drosophila system allowed us to express bacterial proteins in a controlled fashion. We were able to study salmonella infection and the associated proteins and signaling mechanisms in a whole animal, which gave us information we could not have gained from a cell culture dish.”

To evaluate the effects of AvrA in natural salmonella infection in mammals, the scientists used a mouse model of salmonella infection and found that AvrA suppressed the same immune signaling pathways and apoptotic reaction as in the drosophila model. A mutant form of the salmonella lacking the AvrA protein caused an enhanced inflammatory immune response and markedly more cell death in the mouse intestine.

“Using drosophila genetics, we found a biochemical crossroad required for both immune and apoptotic pathways,” says Neish. “The AvrA protein is able to key in on the exact site of the biochemical network and allow it to suppress both the inflammatory response and the apoptotic immune response at the same time. We suspect that other pathogens may target the same biochemical network to avoid elimination. These immune pathways in drosophila have been preserved across evolution and are remarkably similar to human immune pathways. This is such a powerful research system that any bacterial or viral genes would be amenable to study through this approach.”

Media Contact

Sarah Goodwin EurekAlert!

More Information:

http://www.emory.edu

All latest news from the category: Life Sciences and Chemistry

Articles and reports from the Life Sciences and chemistry area deal with applied and basic research into modern biology, chemistry and human medicine.

Valuable information can be found on a range of life sciences fields including bacteriology, biochemistry, bionics, bioinformatics, biophysics, biotechnology, genetics, geobotany, human biology, marine biology, microbiology, molecular biology, cellular biology, zoology, bioinorganic chemistry, microchemistry and environmental chemistry.

Back to home

Comments (0)

Write a comment

Newest articles

Lighting up the future

New multidisciplinary research from the University of St Andrews could lead to more efficient televisions, computer screens and lighting. Researchers at the Organic Semiconductor Centre in the School of Physics and…

Researchers crack sugarcane’s complex genetic code

Sweet success: Scientists created a highly accurate reference genome for one of the most important modern crops and found a rare example of how genes confer disease resistance in plants….

Evolution of the most powerful ocean current on Earth

The Antarctic Circumpolar Current plays an important part in global overturning circulation, the exchange of heat and CO2 between the ocean and atmosphere, and the stability of Antarctica’s ice sheets….

Partners & Sponsors