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When PfAP2-G is stabilized in early asexual parasites, some of them develop into multinucleated schizonts (multiple nuclei appear blue), as predicted by the previous model, but some convert to gametocytes (expressing markers represented in red and green) within the system. same cycle. Credit: Bancells et al.
A study by the Institute for Global Health in Barcelona (ISGlobal) reveals a new mechanism by which the malaria parasite Plasmodium falciparum passes from its asexual form to its sexual form, which can be transmitted to the mosquito. The results, published in Microbiology of naturewill provide important information on the life cycle of the parasite and eventually contribute to design strategies to stop its transmission.
In order for the malaria parasite to be transmissible from one human to another, some blood parasites must stop replicating asexually and convert to sex forms called gametocytes. This sexual conversion is therefore an ideal target to stop parasitic transmission. However, the molecular mechanisms by which this process occurs remain poorly characterized.
Alfred Cortés, ICREA researcher at ISGlobal, and his team used a protein that is only expressed when the cell decides to differentiate into a gametocyte – a time when it can not be distinguished from the asexual phase. Using the CRISPR-Cas9 gene editing technique, they labeled this protein, called PfAP2-G, with a green fluorochrome, and re-examined the hypothesis that, between cell and cellular involvement, sexual conversion, the parasite must undergo a replication cycle.
Using a laboratory culture system, the team discovered that some parasites convert directly to gametocytes without additional replication cycles. "The moment the parasite decided to become a gametocyte turned out to be earlier than expected," Cortes explains. "In fact, although his life cycle was described more than 100 years ago, he continues to surprise us," he adds.
"Our results indicate that parasites that activate PfAP2-G expression early enough during the cycle can take the fast path, while others have to go through a replication cycle before converting to gametocytes," says Cristina. Bancells, first author. "This fast track could promote the survival and transmission of the parasite in a" dangerous "situation, for example in the case of drug treatment," she adds. For the authors, these results provide an extended model for the early stages of sexual differentiation in P. falciparum. They also point to the need for further studies to establish the frequency at which parasites use one or the other route of sexual conversion (conventional as opposed to "express") in vivo.
"It should be noted that gametocytes are a priority target for public health interventions to reduce or even eliminate malaria transmission," said Cortes.
Explore further:
Regulatory protein is key to the life cycle of the malaria parasite
More information:
Cristina Bancells et al, Revisiting the initial stages of sexual development in the malaria parasite Plasmodium falciparum, Microbiology of nature (2018). DOI: 10.1038 / s41564-018-0291-7
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