Zanghí Gigliola, Patel Hardik, Smith Jenny L, Camargo Nelly, Bae Yeji, Hesping Eva, Boddey Justin A, Venugopal Kannan, Marti Matthias, Flannery Erika L, Chuenchob Vorada, Fishbaugher Matthew E, Mikolajczak Sebastian A, Roobsoong Wanlapa, Sattabongkot Jetsumon, Gupta Priya, Pazzagli Lucia, Rezakhani Nastaran, Betz William, Hayes Kiera, Goswami Debashree, Vaughan Ashley M, Kappe Stefan H I
Center for Global Infectious Disease Research, Seattle Children's Research Institute, Seattle, WA, USA.
Research Scientific Computing, Seattle Children's Research Institute, Seattle, WA, USA.
Nat Microbiol. 2025 Feb;10(2):569-584. doi: 10.1038/s41564-024-01905-5. Epub 2025 Jan 31.
Gene expression of Plasmodium falciparum (Pf) liver-stage (LS) parasites has remained poorly characterized, although they are major vaccine and drug targets. Using a human liver-chimaeric mouse model and a fluorescent parasite line (PfNF54GFP), we isolated PfLS and performed transcriptomics on key LS developmental phases. We linked clustered gene expression to ApiAP2, a major family of transcription factors that regulate the parasite life cycle. This provided insights into transcriptional regulation of LS infection and expression of essential LS metabolic and biosynthetic pathways. We observed expression of antigenically variant PfEMP1 proteins and the major Pf protein export machine PTEX and identified protein candidates that might be exported by LS parasites. Comparing Pf and P. vivax LS transcriptomes, we uncovered differences in their expression of sexual commitment factors. This data will aid LS research and vaccine and drug target identification for prevention of malaria infection.
尽管恶性疟原虫（Pf）肝期（LS）寄生虫是主要的疫苗和药物靶点，但其基因表达仍未得到充分表征。利用人肝嵌合小鼠模型和荧光寄生虫系（PfNF54GFP），我们分离出PfLS并对关键的LS发育阶段进行了转录组学分析。我们将聚类的基因表达与ApiAP2联系起来，ApiAP2是调节寄生虫生命周期的主要转录因子家族。这为LS感染的转录调控以及关键LS代谢和生物合成途径的表达提供了见解。我们观察到抗原性变异的PfEMP1蛋白和主要的Pf蛋白输出机器PTEX的表达，并鉴定出可能由LS寄生虫输出的蛋白质候选物。比较Pf和间日疟原虫LS转录组，我们发现了它们在性成熟因子表达上的差异。这些数据将有助于LS研究以及预防疟疾感染的疫苗和药物靶点鉴定。
