The fundamental characteristics of the life cycle of malaria parasites were discovered over a century ago, but some specific steps are not well understood yet. One such step is the transition from asexual blood stages into sexual forms termed gametocytes, necessary for human to mosquito transmission. The results presented in this article modify the previous textbook view of this part of the malaria life cycle.
All malaria clinical symptoms in humans are produced by repeated cycles of exponential asexual parasite growth in the blood. However, transmission of the disease from one human to another via a mosquito vector requires that some of the asexual parasites convert into non-replicating sexual forms termed gametocytes. Gametocytes are the only malaria parasite stages able to infect mosquitoes. For many years, the widely accepted model was that at each cycle of asexual growth a small subset of the parasites commits to sexual conversion, and then they must go through an additional round of multiplication as sexually-committed forms before they actually convert into gametocytes. However, a detailed characterization of the process was previously not possible because molecular markers for sexually-committed forms were not available.
To address this gap of knowledge, we took advantage of our previous identification (in collaboration with other teams) of the PfAP2-G transcription factor as the master regulator of sexual conversion in malaria parasites. Using PfAP2-G as a marker for sexually committed parasites, we found that the additional round of multiplication after sexual commitment is not an obligate step. Thus, parasites can follow two alternative pathways after committing to sexual development: multiplying for one additional cycle before actual conversion into sexual forms (which we termed next cycle conversion route), or converting directly after commitment (same cycle conversion route). The availability of the two alternatives routes provides plasticity to the process, to either increase the output of sexual forms or ensure rapid conversion that may enable survival under harsh conditions.
Reference
Bancells C, Llora-Batile O, Poran A, Notzel C, Rovira-Graells N, Elemento O, Kafsack BFC & Cortes A 2019, ‘Revisiting the initial steps of sexual development in the malaria parasite Plasmodium falciparum’, Nature Microbiology, 4 (1), 144 – 54.
Fig. 1. When malaria parasites multiply asexually in the human blood, the pfap2-g gene is silenced. Activation of the expression of this gene (indicated by red parasite nuclei) results in sexual commitment. After commitment, parasites can convert directly into sexual forms via the same cycle conversion route (SCC), or multiply for one additional cycle as sexually-committed forms before conversion, via the previously known next cycle conversion route (NCC).