Depletion of a fatty molecule in human blood propels malaria parasites to stop replicating and causing illness in people and instead to jump ship to mosquitoes to continue the transmission cycle, according to a new study by an international research team.

The discovery, published online in the journal Cell November 9, answers a longstanding question about what controls this critical step in the life cycle of Plasmodium falciparum, the parasite responsible for about half a million malaria deaths worldwide each year. It could also open doors to new strategies for malaria control and treatment.

The key molecule the researchers identified has the catchy name of lysophosphatidylcholine, or LPC for short. It appears to be a building block the parasites use to construct new cell membranes when they divide, the team found.

“When LPC is plentiful, the parasites happily reproduce in humans,” said J.P. Gerdt, a research fellow in the lab of Jon Clardy at Harvard Medical School and co-first author of the study. “When LPC drops, the parasites can’t multiply anymore and commit to a different pathway.”

“This is a first big step in dissecting the details of what’s going on,” added Gerdt.

The purpose of the research was to illuminate the biochemical motivators in Plasmodium’s decision making. Although important, the findings won’t immediately translate into new therapies, cautioned Clardy, the Hsien Wu and Daisy Yen Wu Professor of Biological Chemistry and Molecular Pharmacology at HMS and co-corresponding author of the study.

Even so, Clardy said, by pinpointing a previously unknown control switch, the work suggests new ways to try to prevent Plasmodium parasites from re-entering mosquitoes and infecting more people—a major goal of global malaria eradication programs.

“Treating patients with antimalarial drugs usually kills the replicating parasites, but if you don’t also block transmission, the disease will never disappear from the population,” said co-corresponding author Matthias Marti, adjunct professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health and professor at the Wellcome Centre for Molecular Parasitology at the University of Glasgow.

Plasmodium parasites lead complex lives. They pass into humans through the bite of an infected Anopheles mosquito, congregating first in the liver and later in red blood cells, where they multiply and burst forth in cycles that cause waves of illness.

Eventually, if the host is lucky enough to survive, some of the parasites stop multiplying and follow a different path known as sexual commitment or differentiation. In what Gerdt likens to a parasitic puberty, they morph from asexual into sexual creatures.

If mosquitoes bite an infected person during this phase, the parasites—now male and female—travel back into the insects and breed. The transmission cycle begins anew.

“Almost everything we try to do to treat malaria is at the blood stage, because that’s when you know people have it,” said Clardy. “Researchers are putting more effort lately into studying the transmission stage in light of campaigns to eliminate malaria.”

Even though sexual commitment is a linchpin in malaria dynamics, scientists didn’t know much about what prompts it. Three years ago, Marti, then an associate professor at the Harvard Chan School, and study co-first author Nicolas Brancucci, then a postdoctoral fellow in Marti’s lab, set out to discover whether any substances in human hosts—rather than in the parasites themselves—played a role.

To find out, they combined their expertise in parasitology with the Clardy lab’s specialty in tracing the source of molecular signals.

When the researchers cultured Plasmodium cells in flasks without their usual bath of human blood serum, the parasites skipped replication and went straight for sexual commitment—hinting that a control