A rotifer-derived paralytic compound prevents transmission of schistosomiasis to a mammalian host

PLoS Biol. 2019 Oct 17;17(10):e3000485. doi: 10.1371/journal.pbio.3000485. eCollection 2019 Oct.

Abstract

Schistosomes are parasitic flatworms that infect over 200 million people, causing the neglected tropical disease, schistosomiasis. A single drug, praziquantel, is used to treat schistosome infection. Limitations in mass drug administration programs and the emergence of schistosomiasis in nontropical areas indicate the need for new strategies to prevent infection. It has been known for several decades that rotifers colonizing the schistosome's snail intermediate host produce a water-soluble factor that paralyzes cercariae, the life cycle stage infecting humans. In spite of its potential for preventing infection, the nature of this factor has remained obscure. Here, we report the purification and chemical characterization of Schistosome Paralysis Factor (SPF), a novel tetracyclic alkaloid produced by the rotifer Rotaria rotatoria. We show that this compound paralyzes schistosome cercariae and prevents infection and does so more effectively than analogous compounds. This molecule provides new directions for understanding cercariae motility and new strategies for preventing schistosome infection.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / chemistry
  • Alkaloids / isolation & purification
  • Alkaloids / pharmacology*
  • Animals
  • Anthelmintics / chemistry
  • Anthelmintics / isolation & purification
  • Anthelmintics / pharmacology*
  • Cercaria / drug effects*
  • Cercaria / pathogenicity
  • Cercaria / physiology
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Female
  • Liver / drug effects
  • Liver / parasitology
  • Male
  • Mice
  • Movement / drug effects
  • Movement / physiology
  • Rotifera / chemistry*
  • Rotifera / isolation & purification
  • Rotifera / metabolism
  • Schistosoma mansoni / drug effects*
  • Schistosoma mansoni / growth & development
  • Schistosoma mansoni / pathogenicity
  • Schistosomiasis / parasitology
  • Schistosomiasis / prevention & control*
  • Schistosomiasis / transmission
  • Skin / drug effects
  • Skin / parasitology
  • Snails / parasitology
  • Solubility
  • Structure-Activity Relationship

Substances

  • Alkaloids
  • Anthelmintics