Genetic and Molecular Basis of Drug Resistance and Species-Specific Drug Action in Schistosome Parasites

TLDR

Schistosoma mansoni spreads through freshwater snails, infects humans via contaminated water, and causes schistosomiasis in about 67 million people, but the parasite has developed resistance to oxamniquine, leaving praziquantel as the sole effective drug. The authors used genetic linkage mapping, genome sequencing, functional genomics, and X‑ray crystallography to investigate the genetic and molecular basis of oxamniquine resistance. They identified specific genetic loci and molecular mechanisms underlying oxamniquine resistance in S. mansoni.

Abstract

Blood Fluke Resistance The larval stages of the blood fluke Schistosoma mansoni are disseminated via a replicative cycle in freshwater snails. When people come into contact with contaminated water, the larvae attach to and penetrate the skin. The resulting disease, bilharzia or schistosomiasis, afflicts approximately 67 million people in Africa and South America. Unfortunately, the parasite is showing resistance to one of the available therapeutic drugs, oxamniquine, which means that schistosome control relies on a single drug, praziquantel. Valentim et al. (p. 1385 , published online 21 November) analyzed the genetic and molecular basis of resistance to oxamniquine through a combination of genetic linkage mapping, genome sequencing, functional genomics analysis, and x-ray crystallography.