Transformation of malaria parasites by the spontaneous uptake and expression of DNA from human erythrocytes.
The uptake and expression of extracellular DNA has been established as a mechanism for horizontal transfer of genes between bacterial species. Such transfer can support acquisition of advantageous elements, including determinants that affect the interactions between infectious organisms and their hosts. Here we show that erythrocyte-stage Plasmodium falciparum malaria parasites spontaneously take up DNA from the host cell cytoplasm into their nuclei. We have exploited this finding to produce levels of reporter expression in P.falciparum that are substantially improved over those obtained by electroporation protocols currently used to transfect malaria parasites. Parasites were transformed to a drug-resistant state when placed into cell culture with erythrocytes containing a plasmid encoding the human dihydrofolate reductase sequence. The findings reported here suggest that the malaria genome may be continually exposed to exogenous DNA from residual nuclear material in host erythrocytes.
Deitsch
K
K
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Driskill
C
C
Wellems
T
T
D000818:Animals; D015139:Blotting, Southern; D004247:DNA / Q000235:genetics*; D004351:Drug Resistance / Q000235:genetics; D004912:Erythrocytes / Q000469:parasitology*; D015870:Gene Expression; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D008727:Methotrexate / Q000494:pharmacology; D010957:Plasmids / Q000235:genetics; D010963:Plasmodium falciparum / Q000187:drug effects / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013762:Tetrahydrofolate Dehydrogenase / Q000235:genetics; D014162:Transfection; D014170:Transformation, Genetic
D011993:Recombinant Fusion Proteins; D004247:DNA; D008156:Luciferases; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate