Global response of Plasmodium falciparum to hyperoxia: a combined transcriptomic and proteomic approach

<p>Abstract</p> <p>Background</p> <p>Over its life cycle, the <it>Plasmodium falciparum </it>parasite is exposed to different environmental conditions, particularly to variations in O₂pressure. For example, the parasite circulates in human venous blood at 5% O₂pressure and in arterial blood, particularly in the lungs, at 13% O₂pressure. Moreover, the parasite is exposed to 21% O₂levels in the salivary glands of mosquitoes.</p> <p>Methods</p> <p>To study the metabolic adaptation of <it>P. falciparum </it>to different oxygen pressures during the intraerythrocytic cycle, a combined approach using transcriptomic and proteomic techniques was undertaken.</p> <p>Results</p> <p>Even though hyperoxia lengthens the parasitic cycle, significant transcriptional changes were detected in hyperoxic conditions in the late-ring stage. Using PS 6.0™ software (Ariadne Genomics) for microarray analysis, this study demonstrate up-expression of genes involved in antioxidant systems and down-expression of genes involved in the digestive vacuole metabolism and the glycolysis in favour of mitochondrial respiration. Proteomic analysis revealed increased levels of heat shock proteins, and decreased levels of glycolytic enzymes. Some of this regulation reflected post-transcriptional modifications during the hyperoxia response.</p> <p>Conclusions</p> <p>These results seem to indicate that hyperoxia activates antioxidant defence systems in parasites to preserve the integrity of its cellular structures. Moreover, environmental constraints seem to induce an energetic metabolism adaptation of <it>P. falciparum</it>. This study provides a better understanding of the adaptive capabilities of <it>P. falciparum </it>to environmental changes and may lead to the development of novel therapeutic targets.</p

Proteomic analysis revealed alterations of the Plasmodium falciparum metabolism following salicylhydroxamic acid exposure

Marylin Torrentino-Madamet1, Lionel Almeras2, Christelle Travaill&amp;eacute;1, V&amp;eacute;ronique Sinou1, Matthieu Pophillat3, Maya Belghazi4, Patrick Fourquet3, Yves Jammes5, Daniel Parzy11UMR-MD3, Universit&amp;eacute; de la M&amp;eacute;diterran&amp;eacute;e, Antenne IRBA de Marseille (IMTSSA, Le Pharo), 2Unit&amp;eacute; de Recherche en Biologie et Epid&amp;eacute;miologie Parasitaires, Antenne IRBA de Marseille (IMTSSA, Le Pharo), 3Centre d&amp;#39;Immunologie de Marseille Luminy, Institut National de la Sant&amp;eacute; et de la Recherche M&amp;eacute;dicale, Centre National de la Recherche Scientifique, Universit&amp;eacute; de la M&amp;eacute;diterran&amp;eacute;e, 4Centre d&amp;#39;Analyse Prot&amp;eacute;omique de Marseille, Institut F&amp;eacute;d&amp;eacute;ratif de Recherche Jean Roche, Facult&amp;eacute; de M&amp;eacute;decine Nord, 5UMR-MD2, Physiologie et Physiopathologie en Conditions d&amp;#39;Oxyg&amp;eacute;nations Extr&amp;ecirc;mes, Institut F&amp;eacute;d&amp;eacute;ratif de Recherche Jean Roche, Facult&amp;eacute; de M&amp;eacute;decine Nord, Marseille, FranceObjectives: Although human respiratory metabolism is characterized by the mitochondrial electron transport chain, some organisms present a &amp;ldquo;branched respiratory chain.&amp;rdquo; This branched pathway includes both a classical and an alternative respiratory chain. The latter involves an alternative oxidase. Though the Plasmodium falciparum alternative oxidase is not yet identified, a specific inhibitor of this enzyme, salicylhydroxamic acid (SHAM), showed a drug effect on P. falciparum respiratory function using oxygen consumption measurements. The present study aimed to highlight the metabolic pathways that are affected in P. falciparum following SHAM exposure.Design: A proteomic approach was used to analyze the P. falciparum proteome and determine the metabolic pathways altered following SHAM treatment. To evaluate the SHAM effect on parasite growth, the phenotypic alterations of P. falciparum after SHAM or/and hyperoxia exposure were observed.Results: After SHAM exposure, 26 proteins were significantly deregulated using a fluorescent two dimensional-differential gel electrophoresis. Among these deregulated proteins, some were particularly involved in energetic metabolism. And the combinatory effect of SHAM/hyperoxia seems deleterious for the growth of P. falciparum.Conclusion: Our results indicated that SHAM appears to activate glycolysis and decrease stress defense systems. These data provide a better understanding of parasite biology.Keywords: Plasmodium falciparum, salicylhydroxamic acid, hyperoxia, glycolysis, proteomi