Nav: Home

Scientists create immunity to deadly parasite by manipulating host's genes

September 16, 2015

There are two common approaches to protecting humans from infectious disease: Targeting pathogens and parasites with medicines such as antibiotics, or dealing with the conditions that allow transmission. Exciting new research demonstrates the effectiveness of a third strategy: adjusting the landscape of the human body to remove the mechanism that allows pathogens to cause disease.

The researchers have silenced genes within human cells to induce immunity to the parasite E. histolytica, which infects 50 million people and causes 40,000 to 110,000 deaths via severe diarrhea worldwide each year. "This amoeba is a cluster bomb - a voracious killer," said Chelsea Marie, PhD, of the University of Virginia School of Medicine, noting the challenge the researchers faced in blocking the amoeba's ability to kill human cells. "In the back of my mind I was thinking the parasite was going to decimate the host cells no matter what we did with their genetics."

Silence Falls

The group used a technique called RNAi to create a library of bladder cancer cells with thousands of independent, silenced genes. Then they challenged these cultures with E. histolytica. "We do this all the time in cancer research," said Dan Theodorescu, MD, PhD, formerly of UVA and now director of the University of Colorado Cancer Center. "Commonly, we're looking for genes that, when silenced, will make cells more susceptible to chemotherapy." In this case, the analogue of chemotherapy was the infectious, dangerous pathogen.

E. histolytica proved a stubborn foe, decimating many thousands of the manipulated cell cultures. However, a small number of cells seemed to resist the parasite. Was this the random chance of lucky survival or had silenced genes somehow provided immunity? To find out, Marie discarded the dead cells and retested the survivors; again she infected the cells with E. histolytica. "It wasn't a fluke," she said. "We did this over nine generations of cells, each time selecting the cells that survived and then re-applying the parasite. Over these generations of selection, we saw the cultures becoming more and more enriched for cells lacking specific genes."

Identifying the Genes Responsible

Using next-generation sequencing, Marie identified the genes that conferred resistance and found that many were involved in managing the flow of potassium into and out of human cells. A follow-up experiment showed that E. histolytica caused intestinal cells to pump out potassium - directly before cell death. "We started to see a pretty clear line of reasoning," Theodorescu said. "The parasite was causing potassium efflux right before cell death and cells that happened to be unable to transport potassium didn't die."

"There is a clear need for new drugs targeting E. histolytica," said Marie's mentor, William A. Petri Jr., MD, PhD, chief of UVA's Division of Infectious Diseases and International Health. "Right now there is a single antibiotic that works against this parasite. We know that eventually the parasite will develop resistance to the antibiotic and at that point there's no plan B. This could be the plan B - targeting the human genes that enable the parasite to cause disease."

The Future

Marie is pushing forward, working to make the technique used in the study more efficient and move it toward use in humans. But just demonstrating it can work is a huge accomplishment. "This is a major finding with translational implications for this infection that causes so many deaths worldwide, but also proof that this cancer-science approach can be used to explore genetic mechanisms of resistance in the field of infectious disease," Theodorescu said.

The findings have been published online by the journal Scientific Reports in an article written by Marie, Hans P. Verkerke, Theodorescu and Petri.
-end-


University of Virginia Health System

Related Cancer Articles:

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.
Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.
Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.
Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.
More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.
New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.
American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.
Oncotarget: Cancer pioneer employs physics to approach cancer in last research article
In the cover article of Tuesday's issue of Oncotarget, James Frost, MD, PhD, Kenneth Pienta, MD, and the late Donald Coffey, Ph.D., use a theory of physical and biophysical symmetry to derive a new conceptualization of cancer.
Health indicators for newborns of breast cancer survivors may vary by cancer type
In a study published in the International Journal of Cancer, researchers from the UNC Lineberger Comprehensive Cancer Center analyzed health indicators for children born to young breast cancer survivors in North Carolina.
Few women with history of breast cancer and ovarian cancer take a recommended genetic test
More than 80 percent of women living with a history of breast or ovarian cancer at high-risk of having a gene mutation have never taken the test that can detect it.
More Cancer News and Cancer Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Speedy Beet
There are few musical moments more well-worn than the first four notes of Beethoven's Fifth Symphony. But in this short, we find out that Beethoven might have made a last-ditch effort to keep his music from ever feeling familiar, to keep pushing his listeners to a kind of psychological limit. Big thanks to our Brooklyn Philharmonic musicians: Deborah Buck and Suzy Perelman on violin, Arash Amini on cello, and Ah Ling Neu on viola. And check out The First Four Notes, Matthew Guerrieri's book on Beethoven's Fifth. Support Radiolab today at Radiolab.org/donate.