Scientists Find New Genetic Path to Deadly Diarrheal Disease

UNLV microbiologist Helen Wing
Jun. 15, 2012

Scientists have found new genetic information that shows how harmful bacteria cause the acute diarrheal disease shigellosis, which kills more than a million people worldwide each year.

The research, which could lead to the development of future treatments, was recently published in the journal PLoS ONE. The study is a collaboration between UNLV microbiologist Helen Wing, former UNLV student Nicholas Egan, Ohio University scientist Erin Murphy, her doctoral student William Broach, and University of Texas at Austin researcher Shelley Payne.

When the disease-causing bacterium Shigella invades a human host, environmental conditions there, such as changes in temperature or pH, stimulate a genetic expression pathway within the bacterium that allows it to survive and cause disease. Central to this genetic pathway are two proteins, VirF and VirB. VirF functions to increase production of VirB which, in turn, promotes the production of factors that increases the bacterium’s virulence, or ability to cause illness in its host.

“This two-step process essentially controls Shigella virulence, and is a major focus of our research program,” said Wing, associate professor in the School of Life Sciences at UNLV.

The new study, however, demonstrates that production of VirB can be controlled independently of VirF. It also shows that the VirF-independent regulation is mediated by a specific small RNA, a special type of molecule whose job is to control the production of particular targets. Regulation mediated by RNA molecules is a major focus of the Murphy lab at Ohio University, Wing explained.

Together, the findings demonstrate that transcription of VirB is regulated by any factor other than VirF. The research not only reveals the intricate level of gene expression the bacteria employs to survive in the human body, but potentially could lead to new treatments.

Currently, antibiotics are prescribed to patients with the disease, but antibiotic resistance is on the rise. This is especially true in developing countries, where mismanagement of antibiotics use continues to lead to antibiotic resistance, said Wing.

“By improving our understanding of the molecular circuitry that controls virulence gene expression in Shigella, it is possible that future researchers can work to disrupt these molecular pathways,” Wing said. “The more we know about Shigella, the more targets we have to disrupt, which may lead to the development of targeted antibiotic treatments.”

For those living in developing countries, where access to clean drinking water can be scarce, an improved medical treatment for shigellosis could mean the difference between life and death.

The disease is transmitted person to person or through contaminated food or water sources. Just 10 organisms can cause disease in a healthy person. Similar disease-causing bacteria require three to four orders of magnitude of organisms to cause sickness.

While shigellosis is often thought to be a third-world problem, it causes a reported 14,000 cases in the United States each year. The Centers for Disease Control suggests that the actual number may be 20 times higher, as mild cases often aren’t reported or diagnosed. In the United States, infants and the elderly are most likely to experience medical complications when infected by Shigella.

The research was funded by the National Institutes of Health, the Ohio University Research Committee, and the Ohio University Heritage College of Osteopathic Medicine.

The full manuscript of the research can be found on the PLoS ONE site.