Discovery provides insight into neglected tropical diseases: Newsroom

Scanning electron micrograph of a pair of pseudostained worms showing a male (blue) and a female (pink). Credit: James Collins and Ana Vieira, UTSW

DALLAS – April 5, 2022 – A team led by UTSW researchers has identified a molecule produced by male parasitic worms called schistosomes that causes sexual maturity in females of these species. The findings, reported in Cellhelp solve a century-old mystery and could lead to new treatments for one of the most important neglected tropical diseases called schistosomiasis, which kills up to 200,000 people a year, according to the World Health Organization (WHO).

James Collins, Ph.D.

“Schistosomiasis doesn’t just affect poor people, it keeps them poor by preventing them from reaching their full potential,” said study leader James Collins, Ph.D., associate professor of pharmacology at UT Southwestern. “Our findings show how understanding the biological processes of these worms could one day offer hope to the hundreds of millions of people infected with these parasites.”

The WHO estimates that around 220 million people have schistosomiasis – mostly children in Africa, Asia and South America. The flatworm parasites that cause this disease have a complicated life cycle that involves stages in freshwater snails and mammals. Living in the circulatory system of mammalian hosts, schistosomes feed on blood and lay large numbers of eggs, which lodge in tissues and organs and cause a range of symptoms including abdominal pain, diarrhea, bloody stools or blood in the urine.

Dr. Collins explained that unlike most flatworm species, which are hermaphroditic, schistosomes have both male and female sexes. Nearly a century ago, researchers discovered that females needed to be in physical contact with males to become and remain sexually mature and to lay the eggs responsible for the symptoms and spread of schistosomiasis. However, the mechanism behind this unusual pathway to puberty is unknown.

To better understand this phenomenon, graduate student Rui Chen, then postdoctoral fellow Jipeng Wang, Ph.D., in the Collins lab, and their colleagues looked for changes in gene activity when male and female schistosomes came into contact. They soon discovered that a gene called gli1 appeared to be essential in males to induce sexual maturity in females. When the researchers deleted gli1 in males, female sex organs remained immature and they never laid eggs.

Because gli1 is a transcription factor responsible for controlling the activity of many genes, the researchers looked for other genes driven by gli1 in males which could be the key to sexual maturity in females. Their research identified a gene they named Schistosoma mansoni non-ribosomal peptide synthetase (Sm-nrps), which links amino acids into short peptides. After showing that Sm-nrps in males is also essential for initiating and maintaining sexual maturity in females, further research has shown that the key product made by this gene is a small peptide called b-alanyl-tryptamine. Dosing female schistosomes with just this peptide was sufficient to initiate and continue sexual maturity, even without the presence of a male.

Dr. Collins noted that because schistosome eggs cause schistosomiasis-related health problems and spread its spread, blocking any part of this pathway could offer a new way to fight this disease. Moreover, although many animals have genes similar to Sm-nrps, none have been reported to play a role in chemical signaling, suggesting the discovery of a previously unrecognized type of animal communication. Dr. Collins said he and his colleagues plan to continue to study this pathway in various species of schistosomes and to search for similar pathways in other animals.

Other UT Southwestern researchers who contributed to this study include Irina Gradinaru, Hieu S. Vu, Sophie Geboers, Jacinth Naidoo, Joseph M. Ready, Noelle S. Williams, Ralph J. DeBerardinis, and Elliott M. Ross.

Dr. Collins is the Rita C. and William P. Clements, Jr. Fellow in Biomedical Research and the Jane and Bud Smith Distinguished Chair in Medicine. Dr. DeBerardinis is a Howard Hughes Medical Institute Scholar, Sowell Family Scholar in Medical Research, and Joel B. Steinberg, MD Distinguished Chair in Pediatrics. Dr. Ross holds the Greer Garson and EE Fogelson Distinguished Chair in Medical Research. Disclosures are included in the manuscript.

This work was supported by grants from the National Institutes of Health (R01AI121037, R01AI150776, and R35CA22044901); The Welch Foundation (I-1948-20180324); and the Burroughs Wellcome Fund.

About UT Southwestern Medical Center

UT Southwestern, one of the nation’s leading academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes and includes 25 members of the National Academy of Sciences, 16 members of the National Academy of Medicine, and 14 researchers from the Howard Hughes Medical Institute. Full-time faculty of more than 2,800 people are responsible for groundbreaking medical advances and committed to rapidly translating scientific research into new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 117,000 inpatients, more than 360,000 emergency room cases, and oversee nearly 3 million outpatient visits annually.

About Terry Gongora

Check Also

Florida Consortium for Medical Marijuana Clinical Outcomes Research: A Beneficial Program

By Dr. Jeff G. Konin As Florida’s marijuana landscape changes rapidly, it’s a good time …