Malaria parasites tolerate a broad range of ionic environments and do not require host cation remodelling.
Malaria parasites grow within erythrocytes, but are also free in host plasma between cycles of asexual replication. As a result, the parasite is exposed to fluctuating levels of Na(+) and K(+) , ions assumed to serve important roles for the human pathogen, Plasmodium falciparum. We examined these assumptions and the parasite's ionic requirements by establishing continuous culture in novel sucrose-based media. With sucrose as the primary osmoticant and K(+) and Cl(-) as the main extracellular ions, we obtained parasite growth and propagation at rates indistinguishable from those in physiological media. These conditions abolish long-known increases in intracellular Na(+) via parasite-induced channels, excluding a requirement for erythrocyte cation remodelling. We also dissected Na(+) , K(+) and Cl(-) requirements and found that unexpectedly low concentrations of each ion meet the parasite's demands. Surprisingly, growth was not adversely affected by up to 148 mM K(+) , suggesting that low extracellular K(+) is not an essential trigger for erythrocyte invasion. At the same time, merozoite egress and invasion required a threshold ionic strength, suggesting critical electrostatic interactions between macromolecules at these stages. These findings provide insights into transmembrane signalling in malaria and reveal fundamental differences between host and parasite ionic requirements.
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
Ajay D
AD
Pillai
Rachel
R
Addo
Paresh
P
Sharma
Wang
W
Nguitragool
Prakash
P
Srinivasan
Sanjay A
SA
Desai
D000818:Animals; D002412:Cations / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology; D003470:Culture Media / Q000494:pharmacology; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects / Q000469:parasitology / Q000648:ultrastructure; D006790:Host-Parasite Interactions; D006801:Humans; D008288:Malaria / Q000469:parasitology*; D052940:Merozoites / Q000187:drug effects / Q000254:growth & development; D009994:Osmolar Concentration; D010271:Parasites / Q000187:drug effects* / Q000254:growth & development; D010710:Phosphates / Q000378:metabolism; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000254:growth & development; D011188:Potassium / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D013395:Sucrose / Q000494:pharmacology; D053058:Trophozoites / Q000187:drug effects / Q000254:growth & development / Q000648:ultrastructure
D002412:Cations; D002712:Chlorides; D003470:Culture Media; D010710:Phosphates; D013395:Sucrose; D012964:Sodium; D011188:Potassium