Definition of constitutive and stage-enriched promoters in the rodent malaria parasite, Plasmodium yoelii
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(2020) 19:424 Bowman et al. Malar J https://doi.org/10.1186/s12936-020-03498-w
Open Access
RESEARCH
Definition of constitutive and stage‑enriched promoters in the rodent malaria parasite, Plasmodium yoelii Laura M. Bowman†, Logan E. Finger†, Kevin J. Hart and Scott E. Lindner*
Abstract Background: Well-defined promoters are essential elements for genetic studies in all organisms, and enable controlled expression of endogenous genes, transgene expression, and gene editing. Despite this, there is a paucity of defined promoters for the rodent-infectious malaria parasites. This is especially true for Plasmodium yoelii, which is often used to study the mosquito and liver stages of malarial infection, as well as host immune responses to infection. Methods: Here six promoters were selected from across the parasite’s life cycle (clag-a, dynein heavy chain delta, lap4, trap, uis4, lisp2) that have been invoked in the literature as controlling their genes in a stage-specific manner. A minimal promoter length for the constitutive pybip promoter that confers strong expression levels was also determined, which is useful for expression of reporters and gene editing enzymes. Results: Instead, it was observed that these promoters confer stage-enriched gene control, as some parasites also effectively use these promoters in other stages. Thus, when used alone, these promoters could complicate the interpretation of results obtained from promoter swaps, stage-targeted recombination, or gene editing experiments. Conclusions: Together these data indicate that achieving stage-specific effects, such as gene editing, is likely best done using a two-component system with independent promoter activities overlapping only in the intended life cycle stage. Keywords: Stage-enriched promoter, Gene editing, Plasmodium yoelii, Malaria parasite Background Malaria remains one of the greatest global health issues today, with hundreds of millions of new infections and nearly half a million fatalities occurring annually [1]. Control of this disease has been challenging due to the nature of the eukaryotic Plasmodium parasites that cause it, the Anopheles mosquitoes that transmit it, and the dynamics of human populations and governments. Despite this, great strides have been made in discovering *Correspondence: [email protected] † Laura M. Bowman and Logan E. Finger have equal contributions Department of Biochemistry and Molecular Biology, The Huck Center for Malaria Research, Pennsylvania State University, University Park, PA, USA
and developing new drugs that can selectively target the parasite, in developing insecticide-treated bed nets that can prevent mosquitoes from biting people, and in advancing subunit and live-attenuated vaccine candidates that can reduce the overall number of malarial infections. However, more interventions are needed to reduce the incidence of malaria as the parasite is able to rapidly evolve drug resistance, and the worldwide diversity of parasite field isolates limits vaccine efficacy. In order to find key we
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