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J Infect Dis. 2013 Jan 1;207(1):164-74. doi: 10.1093/infdis/jis645. Epub 2012 Oct 24.

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

Author information

1
Division of Bacterial, Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, USA.

Abstract

BACKGROUND:

γ-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 γ-radiation-induced cell death in malaria parasites.

METHODS:

The effect of γ-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:

γ-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 γ-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 γ-irradiation attenuation and promising targets for genetic deletion to produce whole parasite-based attenuated vaccines.

PMID:
23100570
PMCID:
PMC3523796
DOI:
10.1093/infdis/jis645
[Indexed for MEDLINE]
Free PMC Article

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