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Science. 2018 May 4;360(6388). pii: eaap7847. doi: 10.1126/science.aap7847.

Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis.

Author information

1
Center for Global Health and Infectious Diseases, Department of Global Health, University of South Florida, 3720 Spectrum Boulevard, Suite 404, Tampa, FL 33612, USA.
2
Malaria Programme, Wellcome Trust Sanger Institute, Genome Campus, Hinxton Cambridgeshire CB10 1SA, UK.
3
Malaria Programme, Wellcome Trust Sanger Institute, Genome Campus, Hinxton Cambridgeshire CB10 1SA, UK. jadams3@health.usf.edu jiang2@health.usf.edu jr9@sanger.ac.uk.
4
Center for Global Health and Infectious Diseases, Department of Global Health, University of South Florida, 3720 Spectrum Boulevard, Suite 404, Tampa, FL 33612, USA. jadams3@health.usf.edu jiang2@health.usf.edu jr9@sanger.ac.uk.

Abstract

Severe malaria is caused by the apicomplexan parasite Plasmodium falciparum. Despite decades of research, the distinct biology of these parasites has made it challenging to establish high-throughput genetic approaches to identify and prioritize therapeutic targets. Using transposon mutagenesis of P. falciparum in an approach that exploited its AT-rich genome, we generated more than 38,000 mutants, saturating the genome and defining mutability and fitness costs for over 87% of genes. Of 5399 genes, our study defined 2680 genes as essential for optimal growth of asexual blood stages in vitro. These essential genes are associated with drug resistance, represent leading vaccine candidates, and include approximately 1000 Plasmodium-conserved genes of unknown function. We validated this approach by testing proteasome pathways for individual mutants associated with artemisinin sensitivity.

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PMID:
29724925
PMCID:
PMC6360947
DOI:
10.1126/science.aap7847
[Indexed for MEDLINE]
Free PMC Article

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