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 language | English (US) |
|---|---|
| Article number | 1638 |
| Journal | Nature communications |
| Volume | 4 |
| DOIs | |
| State | Published - Apr 9 2013 |
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All Science Journal Classification (ASJC) codes
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
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Expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans. / Lim, Caeul; Hansen, Elsa; Desimone, Tiffany M.; Moreno, Yovany; Junker, Klara; Bei, Amy; Brugnara, Carlo; Buckee, Caroline O.; Duraisingh, Manoj T.
In: Nature communications, Vol. 4, 1638, 09.04.2013.Research output: Contribution to journal › Article
TY - JOUR
T1 - Expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans
AU - Lim, Caeul
AU - Hansen, Elsa
AU - Desimone, Tiffany M.
AU - Moreno, Yovany
AU - Junker, Klara
AU - Bei, Amy
AU - Brugnara, Carlo
AU - Buckee, Caroline O.
AU - Duraisingh, Manoj T.
PY - 2013/4/9
Y1 - 2013/4/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84875787172&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84875787172&partnerID=8YFLogxK
U2 - 10.1038/ncomms2612
DO - 10.1038/ncomms2612
M3 - Article
C2 - 23535659
AN - SCOPUS:84875787172
VL - 4
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 1638
ER -