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Radiation-induced cellular and molecular alterations in asexual intraerythrocytic Plasmodium falciparum.

ABSTRACT:

Background

?-irradiation is commonly used to create attenuation in Plasmodium parasites. However, there are no systematic studies on the survival, reversion of virulence, and molecular basis for ?-radiation-induced cell death in malaria parasites.

Methods

The effect of ?-irradiation on the growth of asexual Plasmodium falciparum was studied in erythrocyte cultures. Cellular and ultrastructural changes within the parasite were studied by fluorescence and electron microscopy, and genome-wide transcriptional profiling was performed to identify parasite biomarkers of attenuation and cell death.

Results

?-radiation induced the death of P. falciparum in a dose-dependent manner. These parasites had defective mitosis, sparse cytoplasm, fewer ribosomes, disorganized and clumped organelles, and large vacuoles-observations consistent with "distressed" or dying parasites. A total of 185 parasite genes were transcriptionally altered in response to ?-irradiation (45.9% upregulated, 54.1% downregulated). Loss of parasite survival was correlated with the downregulation of genes encoding translation factors and with upregulation of genes associated with messenger RNA-sequestering stress granules. Genes pertaining to cell-surface interactions, host-cell remodeling, and secreted proteins were also altered.

Conclusions

These studies provide a framework to assess the safety of ?-irradiation attenuation and promising targets for genetic deletion to produce whole parasite-based attenuated vaccines.

SUBMITTER: Oakley MS

PROVIDER: S-EPMC3523796 | biostudies-literature |

REPOSITORIES: biostudies-literature

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