Scientists have isolated a natural chemical that acts as a potent kryptonite against parasitic worms that burrow through human skin and cause devastating health problems. In a paper publishing October 17 in the open-access journal PLOS Biology, a research team led by Phillip Newmark at the Morgridge Institute for Research describe the successful characterization of this chemical, which could help in finding new ways to fight the neglected tropical disease schistosomiasis.
Schistosomiasis, also known as bilharzia, is caused by schistosome infection and affects more than 240 million people in Africa, Asia and parts of South America. In this work the scientists focused on one phase of the schistosome life cycle that could be an intriguing target for preventing infection. Schistosomes seek out freshwater snails as hosts in order to produce millions of tiny fork-tailed creatures called cercaria, which are then unleashed in the water and seek out mammals to infect. Their frenzied swimming allows them to penetrate human skin in minutes.
The story started nearly 40 years ago, when a 1981 paper by Margaret Stirewalt and Fred Lewis of the Biomedical Research Institute in Rockville, Maryland, described the intriguing fact that tiny aquatic creatures called rotifers also live on these snails and release a chemical compound that paralyzes schistosome cercariae on contact. Despite this tantalizing report, scientists had not probed its biochemistry further in the intervening decades.
In the new paper, the Newmark lab and collaborators in Jonathan Sweedler's laboratory at the University of Illinois at Urbana-Champaign report their successful effort to purify and chemically define this molecule, calling it "Schistosome Paralysis Factor" (SPF). Lead author and UW-Madison graduate student Jiarong Gao placed SPF in various concentrations in water and demonstrated that the compound immobilized the cercariae, which promptly sank to the bottom of the water and remained in that state. Further, she showed that cercaria exposed to SPF were unable to infect mice.
Newmark says the results could open a promising new path to controlling schistosomiasis. Currently only a single drug, praziquantel, is used to treat infection and is given to millions of school children each year. But it only kills adult schistosomes and does not stop reinfection.
"Any time you're talking about treating that many people with just one drug and no alternative, you're really concerned about the ability of the parasites to develop resistance," Newmark says. "And that's becoming more and more of an issue as the geographic range of the parasite may be spreading and hybrids between human- and livestock-infecting schistosome species are being reported."
Peer-reviewed; Experimental Study; Animals
In your coverage please use this URL to provide access to the freely available article in PLOS Biology: https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.3000485
Citation: Gao J, Yang N, Lewis FA, Yau P, Collins JJ III, Sweedler JV, et al. (2019) A rotifer-derived paralytic compound prevents transmission of schistosomiasis to a mammalian host. PLoS Biol 17(10): e3000485. https://doi.org/10.1371/journal.pbio.3000485
Funding: This work was supported by: Howard Hughes Medical Institute (https://www.hhmi.org/): Investigator Award to PAN; International Student Research Fellowship to JG; National Institute of Neurological Diseases and Stroke (https://www.ninds.nih.gov/): R01 NS031609 to JVS; National Institute on Drug Abuse (https://www.drugabuse.gov/): P30 DA018310 to JVS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interest: A patent application has been filed by the Wisconsin Alumni Research Foundation and is pending. Use of a Rotifer-Derived Compound and its Analogs for Preventing Schistosomiasis. US Application #: 16/445766, covers the use of this novel molecule and its derivatives in preventing schistosome infection.