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Gametocyte is the sole form of the  Plasmodium falciparum  which is transmissible to the mosquito vector. Here, we report that an Apicomplexan Apetala2 (ApiAP2) family transcription factor, PfAP2-G2 (Pf3D7_1408200), plays a role in the development of gametocytes in  P. falciparum  by regulating the expression of  PfMDV-1 (Pf3D7_1216500) . Reverse transcriptase-quantitative PCR (RT-qPCR) analysis showed that  PfAP2-G2  was highly expressed in the ring stage. Indirect immunofluorescence assay showed nuclear localization of PfAP2-G2 in asexual stages. The knockout of  PfAP2-G2  led to a ~95% decrease in the number of mature gametocytes with a more substantial influence on the production and maturation of the male gametocytes, resulting in a higher female/male gametocyte ratio. To test the mechanism of this phenotype, RNA-seq and RT-qPCR showed that disruption of  PfAP2-G2  led to the down-regulation of male development gene-1 ( PfMDV-1 ) in asexual stages. We further found that PfAP2-G2 was enriched at the transcriptional start site (TSS) of  PfMDV-1  by chromatin immunoprecipitation and qPCR assay in both ring stage and schizont stage, which demonstrated that  PfMDV-1  is one of the targets of PfAP2-G2. In addition, RT-qPCR also showed that PfAP2-G (Pf3D7_1222600), the master regulator for sexual commitment, was also down-regulated in the PfAP2-G2 knockout parasites in the schizont stage, but no change in the ring stage. This phenomenon suggested that PfAP2-G2 played a role at the asexual stage for the development of parasite gametocytes and warrants further investigations in regulatory pathways of PfAP2-G2.

PfAP2-G2 Is Associated to Production and Maturation of Gametocytes in Plasmodium falciparum via Regulating the Expression of PfMDV-1