Host Reticulocytes Provide Metabolic Reservoirs That Can Be Exploited by Malaria Parasites

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Malaria, caused by the Apicomplexan parasites Plasmodium spp., is a deadly disease which poses a huge health and economic burden over many populations in the world, mostly in sub-Saharan Africa and Asia. To design new intervention strategies and to improve upon existing drugs against malaria, it is useful to understand the biochemistry of the Plasmodium parasite and its metabolic interplay with the host. Some species of Plasmodium such as P. vivax grow exclusively in reticulocytes (immature erythrocytes) whereas others e.g. P. falciparum will also readily multiply in mature erythrocytes. We asked the questions, do these two classes of host cell offer different resources for parasite survival and could these resources influence antimalarial drug efficacy? We used metabolomics to compare rodent reticulocytes and mature erythrocytes and identified that the metabolome of the former is more diverse and enriched. Gene disruption in the reticulocyte preferring rodent malaria parasite P. berghei was used to demonstrate that Plasmodium can utilise the elements of the metabolic reserves of reticulocytes that mature erythrocytes cannot provide. Our data suggests that the availability of the reticulocyte metabolome might reduce or block the efficacy of antimalarial drugs that target parasite metabolism and drugs tested against P. falciparum might have significantly reduced activity against P. vivax.

Vyšlo v časopise: Host Reticulocytes Provide Metabolic Reservoirs That Can Be Exploited by Malaria Parasites. PLoS Pathog 11(6): e32767. doi:10.1371/journal.ppat.1004882
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004882

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