An ApiAP2 Family Transcriptional Factor PfAP2-06B Regulates Erythrocyte Invasion Indirectly in Plasmodium falciparum

Obligate intracellular parasites must efficiently invade host cells to complete their life cycle and facilitate transmission. For the malaria-causing parasite <i>Plasmodium falciparum</i>, the invasion of an erythrocyte is a critical process, and thereby a key target for intervention strategies. In this study, we investigate the role of the ApiAP2 family transcription factor PfAP2-06B (PF3D7_0613800) in the intraerythrocytic developmental cycle of <i>P. falciparum</i> and focus on its regulation of genes involved in erythrocyte invasion. Conditional knockdown of PfAP2-06B resulted in a defect in asexual growth and impaired erythrocyte invasion. Bulk RNA sequencing (RNA-seq) analysis revealed that PfAP2-06B modulates the expression of invasion-related genes during the schizont stage. Single-cell RNA sequencing indicated that PfAP2-06B influences invasion gene expression and contributes to stochastic variations in expression of cell-to-cell genes. These results underscore the critical function of PfAP2-06B in the process of erythrocyte invasion and suggest its potential as a target for novel malaria control strategies. Importance: Understanding gene regulation in <i>Plasmodium falciparum</i> is essential for uncovering mechanisms of parasite development and pathogenicity. The research underscores the pivotal role of PfAP2-06B in regulating critical aspects of Plasmodium intraerythrocytic development and host cell invasion, demonstrating that PfAP2-06B plays a key role in orchestrating stage-specific gene expression. These findings provide new insights into the transcriptional networks of P. falciparum and highlight PfAP2-06B as a potential target for therapeutic intervention. This work advances our understanding of malaria pathogenesis and developing effective interventions.