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

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

doi:10.3389/fmicb.2020.631444

Frontiers in Microbiology (Jan 2021)

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

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

Affiliations

Yaozheng Xu: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, China
Dan Qiao: Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Yuhao Wen: Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
Yifei Bi: Philosophy, Politics and Economics Department, University College London, London, United Kingdom
Yuxi Chen: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, China
Zhenghui Huang: Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China
Liwang Cui: Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, United States
Jian Guo: Department of Laboratory Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
Yaming Cao: Department of Immunology, College of Basic Medical Sciences, China Medical University, Shenyang, China

DOI: https://doi.org/10.3389/fmicb.2020.631444
Journal volume & issue: Vol. 11

Abstract

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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.

Published in Frontiers in Microbiology

ISSN: 1664-302X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Microbiology
Website: http://www.frontiersin.org/journals/microbiology

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