Diarrhea; One of the most common causes of diarrhea worldwide accounting for millions of cases; and tens of thousands of deaths, mostly of small children is the parasite Cryptosporidium. Doctors can treat children with Cryptosporidium for dehydration, but unlike many other causes of diarrhea; there are no drugs to kill the parasite or vaccines to prevent infection. But the researchers at Washington University School of Medicine in St Louis have figured out; how to grow the most common type of Cryptosporidium in the lab, a technological advance that will accelerate efforts to treat the deadly infection.
“This parasite was describing over 100 years ago, and scientists was not able to reliably grow it in the lab; however which has hampered our ability to understand the parasite and develop treatments for it. But we now have a way to cultivate it, propagate it, modify its genes and start figuring out how it causes disease in children. This is a first step toward screening potential drugs and finding new drugs or vaccine targets”; said Senior author L. David Sibley, PhD, the Alan A. and Edith L. Wolff Distinguished Professor of Molecular Microbiology.
Screening potential drugs for diarrhea
The findings are published online June 20 in Cell Host & Microbe. In wealthy countries, Cryptosporidium is notorious for causing water-borne outbreaks of diarrhea. Hence, the parasite goes through a complex life cycle, including a stage in which it is called an oocyst and becomes hardy; spore-like and hard to kill with chlorine, bleach or other routine sanitation measures.
In 1993, 400,000 people in the Milwaukee area developed diarrhea; stomach cramps and fever after a malfunctioning water purification plant allowed Cryptosporidium into the city’s water supply. But every year, dozens of smaller outbreaks are reported in the U.S., many associated with swimming pools and water playgrounds. Diarrhea caused by the parasite can last for weeks. While this is miserable for otherwise healthy people; but it can be life-threatening for undernourished children and people with compromised immune systems.
Until now, researchers who wanted to study the parasite had to obtain oocysts from infected calves; Cryptosporidium infection is a serious problem in commercial cattle farming and grow the parasites in human or mouse cell lines. The parasite inevitably would die after a few days without going through a complete life cycle; so the researchers would have to obtain more oocysts from cattle to do more experiments.
Sibley, along with co-first authors Georgia Wilke, PhD, who is a student in the Medical Scientist Training Program; and postdoctoral researcher Lisa Funkhouser-Jones, PhD; suspected that the problem lay in the cell lines traditionally used to grow the parasite. Derived from cancer cells, these cell lines were very different from the normal, healthy intestine that is the parasites’ usual home.
To create a more natural environment, the researchers collaborated with Thaddeus S. Stappenbeck, MD, PhD, the Conan Professor of Laboratory and Genomic Medicine and a co-author on the paper. Stappenbeck and colleagues cultured intestinal stem cells to become “mini-guts” in a dish complete with all the cell types and structural complexity of a real intestine.