Genome-wide gene expression profiles throughout human malaria parasite liver stage development in humanized mice

Zangh&#237;, G; Patel, H; Smith, JL; Camargo, N; Bae, Y; Hesping, E; Boddey, JA; Venugopal, K; Marti, M; Flannery, EL; Chuenchob, V; Fishbaugher, ME; Mikolajczak, SA; Roobsoong, W; Sattabongkot, J; Gupta, P; Pazzagli, L; Rezakhani, N; Betz, W; HAYES, K; Goswami, D; Vaughan, AM; Kappe, SHI

Author(s): Zanghí, G; Patel, H; Smith, JL; Camargo, N; Bae, Y; Hesping, E; Boddey, JA; Venugopal, K; Marti, M; Flannery, EL; Chuenchob, V; Fishbaugher, ME; Mikolajczak, SA; Roobsoong, W; Sattabongkot, J; Gupta, P; Pazzagli, L; Rezakhani, N; Betz, W; HAYES, K; Goswami, D; Vaughan, AM; Kappe, SHI;
Details: Publication Year 2025-02,Volume 10,Issue #2,Page 569-584
Journal Title: Nature Microbiology
Abstract: 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 (PfNF54(CSP)GFP), 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.
Publisher: Springer Nature
Keywords: Animals; Mice; Humans; *Plasmodium falciparum/genetics/growth & development/metabolism; *Liver/parasitology; *Malaria, Falciparum/parasitology; *Transcriptome; *Protozoan Proteins/genetics/metabolism; Disease Models, Animal; Gene Expression Profiling; Life Cycle Stages; Transcription Factors/genetics/metabolism; Plasmodium vivax/genetics/growth & development/metabolism
Research Division(s): Infection and Global Health
PubMed ID: 39891010
Publisher's Version: https://doi.org/10.1038/s41564-024-01905-5
Open Access at Publisher's Site: https://doi.org/10.1038/s41564-024-01905-5
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-02-07 03:05:08

Last Modified: 2025-02-07 03:12:59