Expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans

Caeul Lim, Elsa Hansen, Tiffany M. Desimone, Yovany Moreno, Klara Junker, Amy Bei, Carlo Brugnara, Caroline O. Buckee, Manoj T. Duraisingh

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

The macaque malaria parasite Plasmodium knowlesi has recently emerged as an important zoonosis in Southeast Asia. Infections are typically mild but can cause severe disease, achieving parasite densities similar to fatal Plasmodium falciparum infections. Here we show that a primate-adapted P. knowlesi parasite proliferates poorly in human blood due to a strong preference for young red blood cells (RBCs). We establish a continuous in vitro culture system by using human blood enriched for young cells. Mathematical modelling predicts that parasite adaptation for invasion of older RBCs is a likely mechanism leading to high parasite densities in clinical infections. Consistent with this model, we find that P. knowlesi can adapt to invade a wider age range of RBCs, resulting in proliferation in normal human blood. Such cellular niche expansion may increase pathogenesis in humans and will be a key feature to monitor as P. knowlesi emerges in human populations.

Original languageEnglish (US)
Article number1638
JournalNature communications
Volume4
DOIs
StatePublished - 2013

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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