Author:
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Bancells, Cristina; Llorà Batlle, Oriol; Poran, Asaf; Nötzel, Christopher; Rovira Graells, Núria; Elemento, Olivier; Kafsack, Björn F. C.; Cortés, Alfred
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Abstract:
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Human to vector transmission of malaria requires that
some blood-stage parasites abandon asexual growth and convert
into non-replicating sexual forms called gametocytes. The
initial steps of gametocytogenesis remain largely
uncharacterized. Here, we study this part of the malaria life
cycle in Plasmodium falciparum using PfAP2-G, the master
regulator of sexual conversion, as a marker of commitment. We
demonstrate the existence of PfAP2-G-positive sexually committed
parasite stages that precede the previously known committed
schizont stage. We also found that sexual conversion can occur
by two different routes: the previously described route in which
PfAP2-G-expressing parasites complete a replicative cycle as
committed forms before converting into gametocytes upon
re-invasion, or a direct route with conversion within the same
cycle as initial PfAP2-G expression. The latter route is linked
to early PfAP2-G expression in ring stages. Reanalysis of
published single-cell RNA-sequencing (RNA-seq) data confirmed
the presence of both routes. Consistent with these results,
using plaque assays we observed that, in contrast to the
prevailing model, many schizonts produced mixed plaques
containing both asexual parasites and gametocytes. Altogether,
our results reveal unexpected features of the initial steps of
sexual development and extend the current view of this part of
the malaria life cycle. |