When attempting to protect humankind from infectious disease, experts generally go with one of two widely used approaches. The first is to address the conditions that allow transmission of the disease; the second is to target the pathogen itself with medicines. A third strategy, however, has now been demonstrated in a paper published in the journal Scientific Reports: adjusting the landscape of the human body to remove the mechanism that allows pathogens to cause disease.

This discovery was one part serendipity and one part collaboration between top scientists in various fields.

"It was pure luck that I ended up on this paper," said Dr. Dan Theodorescu, director of the University of Colorado Cancer Center in a press release. "Bill Petri and I had been social friends for years — Christmas parties, that kind of thing. When I was at Virginia it happened that we were on a recruitment committee together and the candidate was late, so we started talking."

It was this conversation with Dr. William A. Petri Jr., chief of the Division of Infectious Diseases & International Health at the University of Virginia, that led to the idea of applying an interesting cancer treatment technique to infectious disease. Along with Dr. Chelsea Marie, postdoctoral researcher in the Petri Laboratory at Virginia and first author of the paper, the researchers tried to silence genes in human cells to see if the loss of any one single gene would confer immunity to the parasite E. histolytica, which is responsible for 40,000-110,000 deaths worldwide via severe diarheaa, according to the press release.

The team used a technique called RNA interference (RNAi) to create a catalogue of bladder cancer cells, each with a different set of silenced genes. They then challenged the different cultures with the parasite. "We do this all the time in cancer research," Theodorescu said in the press release. "Commonly, we're looking for genes that, when silenced, will make cells more susceptible to chemotherapy."

This time, though, instead of chemotherapy, they were working with the infectious pathogen. Marie said she was expecting the parasite to decimate the host cells no matter how they tinkered with the genetics. But a small number of cells were actually able to resist the parasite, and Marie wanted to find out if this was simply luck or the power of the silenced genes. To find out, she infected the surviving cells yet again with E. histolytica.

"It wasn't a fluke," said Marie in the press release. "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."

Petri says there is a clear need for new and effective drugs to treat E. histolytica. Currently, there is only one known antibiotic that works against the parasite, and eventually the parasite will develop a resistence to it. In this case, there would be no plan B — except for possibly this new gene manipulation.

The team plans to push forward with their research.

"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.

Source: Marie C, et al. Nature: Study Creates Cell Immunity To Parasite That Infects 50 Million. Scientific Reports. 2015.