AUTHOR=Xu Yaozheng , Qiao Dan , Wen Yuhao , Bi Yifei , Chen Yuxi , Huang Zhenghui , Cui Liwang , Guo Jian , Cao Yaming 

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

JOURNAL=Frontiers in Microbiology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2020.631444

DOI=10.3389/fmicb.2020.631444

ISSN=1664-302X

ABSTRACT=<p>Gametocyte is the sole form of the <italic>Plasmodium falciparum</italic> 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 <italic>P. falciparum</italic> by regulating the expression of <italic>PfMDV-1 (Pf3D7_1216500)</italic>. Reverse transcriptase-quantitative PCR (RT-qPCR) analysis showed that <italic>PfAP2-G2</italic> was highly expressed in the ring stage. Indirect immunofluorescence assay showed nuclear localization of PfAP2-G2 in asexual stages. The knockout of <italic>PfAP2-G2</italic> 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 <italic>PfAP2-G2</italic> led to the down-regulation of male development gene-1 (<italic>PfMDV-1</italic>) in asexual stages. We further found that PfAP2-G2 was enriched at the transcriptional start site (TSS) of <italic>PfMDV-1</italic> by chromatin immunoprecipitation and qPCR assay in both ring stage and schizont stage, which demonstrated that <italic>PfMDV-1</italic> 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.</p>