The Bacteria Battle : Scientist Erin Murphy uncovers the genetic mechanisms behind a deadly disease
By Elizabeth Boyle
Feb. 12, 2013
Few Americans need to worry about access to clean drinking water. When we get sick and lose bodily fluids—when staying hydrated could mean life or death—sanitary water and liquids with electrolytes are readily available from our kitchen faucets or supermarket shelves.
That's not the case everywhere. In developing countries, an estimated 780 million people rely on unsafe water sources. The lack of potable water not only causes a variety of illnesses and health issues, but it also puts people in real peril once an illness strikes and they can't replenish lost fluids.Ohio University bacteriologist Erin Murphy knows something about those consequences. She’s spent the past decade studying the deadly bacterium Shigella, which causes an acute diarrheal illness known as shigellosis. The disease kills more than a million people worldwide each year, although the Centers for Disease Control and Prevention estimates that could represent just one fourth of the actual global count due to underreported incidents and under diagnosis. Many of the deaths, though not all, occur in developing countries.
Erin Murphy (photo by John Sattler)
“This is a really highly virulent pathogen,” Murphy says of the bacterium, which is transmitted person to person or through contaminated food or water sources. “It has an infectious dose of just 10 organisms, meaning as little as 10 bacteria can cause disease in a healthy person.”
This infectious dose is exceedingly low compared to other bacteria that require tens of thousands of organisms to cause disease, she explains. Murphy’s mission is to provide a better understanding of the genetics behind how these lethal microorganisms cause illness. Her latest work, which was funded in part by the National Institutes of Health, was published this summer in the high-impact scientific journal PLOS ONE.
The project focused on the domino-like action of two proteins in the bacteria’s genetic code. When the bacteria enter a human host, environmental conditions there—changes in temperature or pH, for example—stimulate expression of a genetic 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. Murphy’s findings, however, suggested something different. They showed that production of VirB can be controlled independently of VirF. They also demonstrated 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.
The research, which was the first to demonstrate that transcription of virB is regulated by any factor other than VirF, revealed the intricate level of gene expression the bacteria employ to survive in the human body. It could also lead to new treatments.
“These findings are feeding into the basic understanding of this gene expression so that future researchers can work to disrupt it,” says Ohio University doctoral student William Broach, who contributed to the study. “The more we know about it, the more targets we have to disrupt it and to possibly develop targeted antibiotic treatments.”
By “targeted antibiotic treatments,” Broach refers to new medications that could impede bacterial functions, such as the ability to cause damage in a host. Such new treatments could help decrease antibacterial resistance by providing treatments specific to the infecting bacteria. Currently, patients with the disease are treated with general antibiotics.
To conduct the study, Murphy and Broach used standard genetic methods to introduce new sequences into Shigella genes. Working with collaborators from University of Nevada, Las Vegas, and University of Texas at Austin, they then tested the affected bacteria on tissue cultures of intestinal cells to see if the bacteria had more or less virulence under each condition they tried.
Murphy has been working on similar studies at Ohio University’s Heritage College of Osteopathic Medicine since joining the faculty in 2008. She began her career in bacteriology studying Bordetella, the bacteria that cause whooping cough, and she transitioned to research on Shigella virulence as a postdoctoral researcher at the University of Texas at Austin. After initially investigating how iron levels affect the bacteria, she said, each subsequent study has generated new questions to investigate.
“I’ve always liked the puzzle aspect of a gene regulation pathway,” she says. “I like figuring out how these things work together to affect something else.”
Other puzzles she’s working on include determining how Shigella regulates the production of the proteins it needs to get iron in the human body. Another diverges from her typical genetics research on Shigella and is related to several cases of bacterial meningitis recorded among Ohio University students in 2009 and 2010. It seeks links between the strain of bacteria associated with the cases and certain behaviors or health factors.
Murphy’s findings could give area health experts much needed information about the cases, and it could help inform colleges nationwide about risks associated with contracting the deadly disease.
“We have 10 times more bacteria on our body than we do human cells. They’re important to human health,” she explains. “But we see meningitis in close quarters, like college campuses, where people share close quarters. We want to learn what could put people at risk to get it.”
No matter the project, Murphy is always working on something she’s enjoyed since she was a girl: science. Always partial to biology, she fell in love with it while working summers in high school and college in the microbiology lab of a cousin who studies ear and lung infections at the University of Buffalo. Although she briefly considered medical school in college, she knows she’s in the right line of work.
“I like that what I do is medically relevant,” she says. “Hopefully somebody else will see what I do, incorporate it into their studies and down the road it will translate into a new treatment,” she says.
That treatment? It could help people a half a world away, or on her own college campus.
This article appears in the Autumn/Winter 2012 issue of Perspectives magazine.