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Review
. 2015 May 11:6:391.
doi: 10.3389/fmicb.2015.00391. eCollection 2015.

Enlightening the malaria parasite life cycle: bioluminescent Plasmodium in fundamental and applied research

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Review

Enlightening the malaria parasite life cycle: bioluminescent Plasmodium in fundamental and applied research

Giulia Siciliano et al. Front Microbiol. .

Abstract

The unicellular protozoan parasites of the genus Plasmodium impose on human health worldwide the enormous burden of malaria. The possibility to genetically modify several species of malaria parasites represented a major advance in the possibility to elucidate their biology and is now turning laboratory lines of transgenic Plasmodium into precious weapons to fight malaria. Amongst the various genetically modified plasmodia, transgenic parasite lines expressing bioluminescent reporters have been essential to unveil mechanisms of parasite gene expression and to develop in vivo imaging approaches in mouse malaria models. Mainly the human malaria parasite Plasmodium falciparum and the rodent parasite P. berghei have been engineered to express bioluminescent reporters in almost all the developmental stages of the parasite along its complex life cycle between the insect and the vertebrate hosts. Plasmodium lines expressing conventional and improved luciferase reporters are now gaining a central role to develop cell based assays in the much needed search of new antimalarial drugs and to open innovative approaches for both fundamental and applied research in malaria.

Keywords: Plasmodium; bioluminescence; cell-based screening assays; in vivo imaging; malaria; reporter genes.

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Figures

FIGURE 1
FIGURE 1
Transgenic bioluminescent malaria parasites at different stages of their development in the vertebrate and mosquito hosts. The central diagram represents the Plasmodium life cycle, showing the progression through the developmental stages of the parasites in the mosquito vector and in the vertebrate host. (A) Bioluminescence imaging (BLI) of individual Plasmodium falciparum gametocytes expressing a click beetle luciferase under a sexual stage-specific promoter. The bright field image shows immobilized gametocytes, highlighted in green, amongst uninfected erythrocytes; the dark field shows the bioluminescence signal of the gametocytes incubated with D-luciferin. Magnification bar: 15 μm. (Adapted from Cevenini et al., 2014). (B) BLI of a mouse infected with asexual P. berghei parasites expressing a firefly luciferase-green fluorescent protein (GFP) fusion. Heatmap of the bioluminescent signal identifies the sites of accumulation of the parasites (Reproduced with permission from Claser et al., 2011). (C) Fluorescence of a firefly luciferase-GFP fusion protein expressed in P. falciparum sporozoites contained in a oocyst and (D) obtained from the dissection of infected mosquito salivary glands. Magnification bar: 5 μm. (E) In vivo bioluminescent signal obtained by transgenic P. falciparum liver stage parasites developing in the chimeric liver of a humanized mouse (C–E) are reproduced with permission from Vaughan et al. (2012).

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