Researchers at the Stanford University School of Medicine and the University of California-San Francisco have developed a novel technique to “tame” the malaria parasite, by forcing it to depend on an external supply of a vital chemical.
The scientists have, in effect, created a domesticated strain of Plasmodium — the one-celled parasite that causes malaria — that would no longer cause this dreaded disease.
At the heart of the paper is a discovery by Ellen Yeh, MD, PhD, an instructor in Stanford”s Department of Pathology, and UCSF professor of biochemistry and biophysics and Howard Hughes Medical Institute investigator Joseph DeRisi.
The scientists identified isopentenyl pyrophosphate, or IPP, as absolutely essential to the malaria parasite”s viability during the stage when it invades blood cells.
Normally, Plasmodium”s IPP supply is manufactured in a unique structure within the parasite, called the apicoplast. IPP is pivotal to Plasmodium”s survival, but the researchers showed that during its blood-infecting stage, the parasite can live without its apicoplast — as long it continues to get IPP from another source.
Malaria is transferred to humans via a mosquito bite, during which one-celled parasites of the genus Plasmodium are injected into the bloodstream.
The researchers dosed blood-rich cultures of the parasite with antibiotics. It is known that antibiotics cause Plasmodium to cast off its apicoplast. This eventually causes the organism”s death, but too slowly for antibiotics to be of any significant therapeutic use by themselves (although they can be used as prophylactics or in combination with other, faster-acting drugs).
They found that if they added antibiotics to the culture medium along with a single substance, IPP, the apicoplast-lacking parasites could thrive in culture.
“This showed that IPP is the only product Plasmodium really needs from its apicoplast during its blood stage,” said Yeh.
This first-ever cultivation of an apicoplast-free malaria parasite promises to advance efforts to come up with new drug and vaccine leads.
“This potential pathway for killing parasites without interfering with human cells is the reason the apicoplast has been a major focus for drug development,” said Yeh.
“Now we have a way to specifically look for drugs that target its function and discover a whole new class of desperately needed anti-malarials,” added Yeh.
The study has been published in PLoS Biology.