Nature microbiology · 2025
Genome-wide gene expression profiles throughout human malaria parasite liver stage development in humanized mice.
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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
Аннотация
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 (PfNF54CSPGFP), 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.