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

IF 20.5 1区生物学 Q1 MICROBIOLOGY

Nature Microbiology Pub Date : 2025-01-31 DOI:10.1038/s41564-024-01905-5

Gigliola Zanghí, Hardik Patel, Jenny L. Smith, Nelly Camargo, Yeji Bae, Eva Hesping, Justin A. Boddey, Kannan Venugopal, Matthias Marti, Erika L. Flannery, Vorada Chuenchob, Matthew E. Fishbaugher, Sebastian A. Mikolajczak, Wanlapa Roobsoong, Jetsumon Sattabongkot, Priya Gupta, Lucia Pazzagli, Nastaran Rezakhani, William Betz, Kiera Hayes, Debashree Goswami, Ashley M. Vaughan, Stefan H. I. Kappe

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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 (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. Transcriptomics of gene expression in Plasmodium falciparum liver-stage parasites reveals transcriptional regulation, metabolic pathways and antigen expression, facilitating vaccine and drug target identification.

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来源期刊

Nature Microbiology Immunology and Microbiology-Microbiology

CiteScore

44.40

自引率

1.10%

发文量

226

期刊介绍： Nature Microbiology aims to cover a comprehensive range of topics related to microorganisms. This includes: Evolution: The journal is interested in exploring the evolutionary aspects of microorganisms. This may include research on their genetic diversity, adaptation, and speciation over time. Physiology and cell biology: Nature Microbiology seeks to understand the functions and characteristics of microorganisms at the cellular and physiological levels. This may involve studying their metabolism, growth patterns, and cellular processes. Interactions: The journal focuses on the interactions microorganisms have with each other, as well as their interactions with hosts or the environment. This encompasses investigations into microbial communities, symbiotic relationships, and microbial responses to different environments. Societal significance: Nature Microbiology recognizes the societal impact of microorganisms and welcomes studies that explore their practical applications. This may include research on microbial diseases, biotechnology, or environmental remediation. In summary, Nature Microbiology is interested in research related to the evolution, physiology and cell biology of microorganisms, their interactions, and their societal relevance.