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‘Domino Effect’ Key To Unlocking Shigella Mysteries

Diarrheal diseases are the second leading cause of death, after lower respiratory tract infections, for children under age 5. Of these deaths, a full 75 percent are from shigellosis.

Yet Shigella, the Gram-negative bacterium transmitted via contaminated food or water, does not seem to get the attention it’s due for the worldwide devastation it causes.

According to the World Health Organization, Shigellosis is responsible for 90 million illnesses and 108,000 deaths annually. And while viewed as a Third World disease, WHO says there are half a million cases each year involving military personnel and travelers from industrialized countries.

The United States sees about 14,000 shigellosis cases each year, but the federal Centers for Disease Control and Prevention (CDC) in Atlanta says the actual number is probably 20 times higher, as most cases go unreported and are self-treated at home.

Now a team of researchers from three American universities, led by Dr. Erin Murphy, assistant professor of bacteriology at the Ohio University Heritage College of Osteopathic Medicine, is shedding new light on this old plague.


“Our work furthers the understanding of how Shigella responds to the environmental conditions encountered within the human body to control the production of bacterial factors that increase the ability of the bacteria to cause the disease,” Murphy told Food Safety News.

“Understanding how bacteria control the production of such ‘virulence factors’ may, one day, lead to therapeutics that specifically disrupt these processes, ” she continued.  “Our work is the basic science that may support future applied studies by others.”

The research by the OU, University of Nevada, Las Vegas, and University of Texas at Austin team was published in the journal PLoS ONE. Murphy’s collaborators are scientists Nicholas Egan and Helen Wing at UNLV and researcher Shelley Payne in Austin.  William Broach, an OU doctoral student, was the other contributor.

The team found that new genetic information shows how exactly harmful Shigella bacteria cause acute diarrheal disease, resulting in more than one million deaths worldwide each year.

The groundbreaking research discovered two important proteins that help determine just how virulent a case of shigellosis (the disease caused by Shigella infection) will become. It’s something Murphy calls the “domino effect,” she says. Food Safety News asked her to explain.

“By the ‘domino effect,’ I was referring to the regulatory pathway known to control the production of many Shigella virulence factors.  Specifically, the protein VirF functions to promote the production of the protein VirB that in turn functions to promote the production of several important virulence factors,” she explained.

In other words, one protein promotes the production of another, which promotes the production of the next, causing a domino effect of proteins that contribute to Shigella’s virulence.

“The domino analogy works because once VirF is active, a series of steps is initiated that ultimately results in the production of the factors that promote infection (virulence factors).  Our study shows that the production of VirB (specifically that transcription of the virB gene) can be uncoupled from the activity of VirF, thus revealing a novel regulation event influencing VirB production.

“Without VirB produced, Shigella cannot cause disease, so the more we know about how VirB production is regulated, the better the chance that production of this protein many one day be successfully targeted (inhibited) by an anti-Shigella therapeutic,” says Murphy.

Now that researchers know how the genetic path works, their next step will be to work on how to disrupt it, maybe with targeted antibiotic treatments that could be critical in helping people with shigellosis in developing countries.

Murphy says healthy Americans with access to clean water might get the diarrhea too, but they are not going to die from their infections, unlike children in developing countries.

Nevertheless Murphy says it’s important to take precautions against Shigella infection here in the U,S, too.

“Shigella is transmitted by direct ingestion of infected fecal matter (on unwashed hands for example) or by ingestion of food or water that is contaminated by infected fecal matter and that very few bacteria (as few as 10) need to be ingested to cause disease in a healthy person,” Murphy says.

“For this reason, clean water sources are of utmost importance in preventing the spread of Shigellosis in the developing world.  In areas of the world with clean water sources, careful hand washing and general good hygiene technique can effectively prevent the spread of Shigellosis,” she adds.

The National Institutes of Health, the Ohio University Research Committee, and the Ohio University Heritage College of Osteopathic Medicine funded the team’s research.

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