Malaria: Newly identified “crown” stage controls parasite reproduction

(Press-News.org) Researchers studying the malaria parasite Plasmodium falciparum have discovered a previously unknown stage in its life cycle that appears to be crucial for reproduction. This is important because malaria depends on the parasite’s rapid ability to multiply inside the human body, so stopping its reproduction could help prevent severe disease and save lives. Using a new live-imaging method, the team found that before the parasite can divide, a key structure inside the cell must reshape into a “Crown” form and connect to the cell’s nucleus. This step helps ensure that essential parts of the parasite are properly passed on to its new daughter cells. The findings point to a promising new target for future malaria treatments: interrupting the signals that control this “Crown” stage could potentially stop the parasite from multiplying.

A new study has uncovered a hidden step that helps the deadliest malaria parasite survive and multiply inside the human body. Researchers studying Plasmodium falciparum found that the parasite relies on a brief but essential stage, nicknamed the “Crown” stage, to make sure a crucial internal structure is passed on correctly when it divides. The discovery offers a fresh look at how the parasite reproduces and could point to new ways to stop malaria by disrupting this process.

Malaria remains one of the world’s most devastating infectious diseases, causing hundreds of thousands of deaths each year, most of them among young children in sub-Saharan Africa.

The research, published in the Journal of Cell Biology, was led by Dr. Anat Florentin of The Kuvin Center for the Study of Infectious and Tropical Diseases and the Department of Microbiology and Molecular Genetics in the Faculty of Medicine at Hebrew University. The team focused on a tiny structure inside the parasite called the apicoplast. While humans don’t have this organelle, malaria parasites depend on it to survive. Although the apicoplast originally came from a photosynthetic ancestor, it now functions as a kind of mini chemical factory, producing essential molecules, including fatty acids and isoprenoids, that the parasite needs to grow inside human red blood cells.

“By tracking both DNA replication and apicoplast development in real time, we found the details of these events and what controls them,” says Dr. Florentin. “There are both signals from the nucleus and intrinsic organelle cues at play. These mechanisms could provide a new opportunity for drug development: if, for example, we can interrupt the communication between the nucleus and the apicoplast, we will stop the parasite from multiplying.”

To observe what happens inside the parasite as it grows, the researchers developed an advanced live-imaging system that follows subcellular structures in high resolution across the parasite’s full 48-hour life cycle. Using this approach, they identified four stages in apicoplast development: Elongation, Branching, Crown, and Division.

The study highlights the importance of the Crown stage, a short one-hour period just before the parasite divides. During this phase, the apicoplast stretches across multiple nuclei and attaches to structures known as centriolar plaques, the parasite’s equivalent of the machinery that helps cells organize division. This connection acts like a distribution checkpoint, helping ensure that when the parasite splits, every new daughter cell receives one complete, working apicoplast.

To understand how this process is controlled, the researchers used drugs that block specific steps in the parasite’s replication:

Blocking nuclear DNA replication: When the researchers stopped the parasite from copying its nuclear DNA using aphidicolin, apicoplast development stalled almost immediately. This showed that the apicoplast cannot grow properly unless the parasite has entered the DNA-copying phase of its cycle. Blocking apicoplast DNA replication: In contrast, when the team blocked the apicoplast’s own DNA replication using ciprofloxacin (CIP), the organelle still grew and formed branches but it failed to form the Crown structure. Without the Crown stage, the apicoplast could not attach to the centriolar plaques, and daughter cells were produced without it. This leads to a phenomenon known as “delayed death.” The first generation of parasites may survive, but the next generation cannot, because without the apicoplast, the parasite is missing a structure it needs to make essential molecules and stay alive.

Overall, the findings challenge the idea that the apicoplast functions independently inside the parasite. Instead, the study suggests that the apicoplast’s development and inheritance depend on carefully timed signals from the parasite’s nucleus, especially during the newly identified Crown stage.

According to the researchers, this newly uncovered dependency may represent a promising vulnerability. By targeting the signaling mechanisms that coordinate the parasite’s DNA replication and apicoplast development, future therapies could disrupt parasite reproduction and help stop malaria by preventing the parasite from multiplying in the first place.

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