Division and Adaptation to Host Environment of Apicomplexan Parasites Depend on Apicoplast Lipid Metabolic Plasticity and Host Organelle Remodeling

• Published in: Cell reports (Cambridge) Vol. 30; no. 11; pp. 3778 - 3792.e9
• Main Authors: Amiar, Souad, Katris, Nicholas J., Berry, Laurence, Dass, Sheena, Duley, Samuel, Arnold, Christophe-Sebastien, Shears, Melanie J., Brunet, Camille, Touquet, Bastien, McFadden, Geoffrey I., Yamaryo-Botté, Yoshiki, Botté, Cyrille Y.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.03.2020; Elsevier
• Subjects: Acyltransferases - metabolism; Adaptation, Physiological; Animals; Apicomplexa; apicoplast; Apicoplasts - metabolism; Biochemistry, Molecular Biology; Cancer; Cell Division; Cell Membrane - metabolism; Cellular Biology; Cytokinesis; Fatty Acid Synthases - metabolism; Fatty Acids - biosynthesis; Gene Deletion; host nutritional environment; host-parasite interaction; Host-Parasite Interactions; Human health and pathology; Humans; Infectious diseases; Intracellular Space - parasitology; Life Cycle Stages; Life Sciences; Lipid Metabolism; lipid synthesis; Lipidomics; malaria; Male; Microbiology and Parasitology; Models, Biological; Multivesicular Bodies - metabolism; Multivesicular Bodies - ultrastructure; Mutation - genetics; Nutrients; Parasites - growth & development; Parasites - metabolism; Parasites - physiology; Parasites - ultrastructure; Parasitology; phosphatidic acid; Protozoan Proteins - metabolism; Quantitative Methods; Toxoplasma - growth & development; Toxoplasma - metabolism; Toxoplasma - physiology; Toxoplasma - ultrastructure; toxoplasmosis; Vegetal Biology; Apicomplexa; lipid synthesis; host nutritional environment; toxoplasmosis; cytokinesis; host-parasite interaction; phosphatidic acid; malaria; lipidomics; apicoplast
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.02.072

Apicomplexan parasites are unicellular eukaryotic pathogens that must obtain and combine lipids from both host cell scavenging and de novo synthesis to maintain parasite propagation and survival within their human host. Major questions on the role and regulation of each lipid source upon fluctuating host nutritional conditions remain unanswered. Characterization of an apicoplast acyltransferase, TgATS2, shows that the apicoplast provides (lyso)phosphatidic acid, required for the recruitment of a critical dynamin (TgDrpC) during parasite cytokinesis. Disruption of TgATS2 also leads parasites to shift metabolic lipid acquisition from de novo synthesis toward host scavenging. We show that both lipid scavenging and de novo synthesis pathways in wild-type parasites exhibit major metabolic and cellular plasticity upon sensing host lipid-deprived environments through concomitant (1) upregulation of de novo fatty acid synthesis capacities in the apicoplast and (2) parasite-driven host remodeling to generate multi-membrane-bound structures from host organelles that are imported toward the parasite. [Display omitted] •Knockout of apicoplast TgATS2 disrupts LPA/PA for DrpC recruitment during cytokinesis•T. gondii can sense host environment and adapt to low host nutritional content•Under lipid starvation, parasite FASII and other lipid metabolic genes become essential•Upon nutrient deprivation, T. gondii induces host organelle remodeling and vesiculation Apicoplast de novo lipid synthesis and lipid host scavenging are both critical for apicomplexan intracellular development. Amiar et al. show that the parasite adapts to the fluctuations of host nutritional content to regulate the metabolic activity of both apicoplast and scavenging pathways and maintain parasite development and division.