Bacterial pathogens studied as agents for new diseases

By Kristen Holland Shear

Microbiologists at UT Southwestern have identified how bacterial pathogens such as shigella, salmonella and a strain of Escherichia coli, working at the molecular level, could potentially cause new diseases.

In a study in Nature Structural & Molecular Biology, researchers describe how these diarrhea-causing pathogens effectively exploit a family of human proteins present in our cells to do their dirty work. To do this, bacteria inject toxins directly into our own cells, creating new “docking points” where pathogens latch on to start replicating. When bacteria invade an organism, they essentially use these toxins to hijack the ability of human cells to communicate. The end result: They evade the human immune system.

Dr. Neal Alto, assistant professor of microbiology and co-lead author of the study, said, “There is a reservoir, or pool, of toxin proteins being used by numerous pathogens to delay communication among our immune response systems.”

Dr. Neal Alto

In this new study, however, Dr. Alto and his colleagues uncovered how very different bacteria such as shigella, salmonella and a strain of E coli known as EHEC 0157 can genetically alter their toxin pool, allowing them to not only avoid immune detection, but also to cause new diseases.

Dr. Alto said this new information suggests that researchers may be able to prevent illness by targeting these protein pools instead of a single pathogen itself.

“The goal of many new drugs is to allow your immune system to become more efficient compared to the bacteria,” he said. “Developing drugs to target these proteins would likely inhibit a pathogen’s ability to take over our cells by delaying the bacteria from colonizing and replicating as rapidly.”

Knowing that multiple pathogens share a pool of such proteins could also be important as new, emerging pathogens continue to pop up around the world.

“This information allows us to extrapolate very quickly the life cycle of a new organism,” Dr. Alto said. “The next time a new pathogen emerges, we don’t have to go back and recharacterize it. We can compare it to similar, known organisms and have a head start in knowing how it will likely behave, as well as whether there’s an existing drug to target it.”

He stressed that alternative drug targets may not be more efficient than existing therapies.

“It would be an alternative or addition to current antibiotic therapies for bacteria that we clearly know are becoming more resistant,” he said. “It’s a way of us getting a leg up on the bacteria because they haven’t seen this approach yet.”

The next step, he said, is to study more pools of toxin proteins so researchers can better understand how they are being adapted by each organism.

Other UT Southwestern researchers involved in the study were Sarah Sutton, research assistant in microbiology, as well as Adam Wallenfang and Robert Orchard, student research assistants in microbiology.

This study was supported by the Welch Foundation; Texas’ Advanced Research Program, now called the Norman Hackerman Advanced Research Program; and the Chinese Ministry of Science and Technology.