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A Novel Tool for the Generation of Conditional Knockouts To Study Gene Function across the Plasmodium falciparum Life Cycle

2019; American Society for Microbiology; Volume: 10; Issue: 5 Linguagem: Inglês

10.1128/mbio.01170-19

2161-2129

Marta Tibúrcio, Annie Yang, Kazuhide Yahata, Pablo Suárez-Cortés, Hugo Belda, Sebastian Baumgarten, Marga van de Vegte‐Bolmer, Geert‐Jan van Gemert, Youri van Waardenburg, Elena A. Levashina, Robert W. Sauerwein, Moritz Treeck,

vaccines and immunoinformatics approaches

One of the major limitations in studying P. falciparum is that so far only asexual stages are amenable to rapid conditional genetic modification. The most promising drug targets and vaccine candidates, however, have been refractory to genetic modification because they are essential during the blood stage or for transmission in the mosquito vector. This leaves a major gap in our understanding of parasite proteins in most life cycle stages and hinders genetic validation of drug and vaccine targets. Here, we describe a method that supports conditional gene deletion across the P. falciparum life cycle for the first time. We demonstrate its potential by deleting essential and nonessential genes at different parasite stages, which opens up completely new avenues for the study of malaria and drug development. It may also allow the realization of novel vaccination strategies using attenuated parasites.