Phosphatidic acid as a limiting host metabolite for the proliferation of the microsporidium Tubulinosema ratisbonensis in Drosophila flies

Franchet, Adrien; Niehus, Sebastian; Caravello, Gaëtan; Ferrandon, Dominique

doi:10.1038/s41564-018-0344-y

Cited by 41 publications

(29 citation statements)

References 51 publications

(66 reference statements)

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“…Although it is currently not possible to genetically modify microsporidia, using RNAi to knockdown genes provides a powerful approach to directly study microsporidia protein function in the context of infection [44,49]. Finally, the discovery of microsporidia that infect model organisms such as C. elegans and Drosophila melanogaster provides easily cultured, genetically tractable hosts for studying how microsporidia function [2,19,35,50]. Continued use of the technological advances highlighted here is likely to provide additional insight into the function and evolution of these fascinating pathogens.…”

Section: Future Perspectivementioning

confidence: 99%

Evolution of microsporidia: An extremely successful group of eukaryotic intracellular parasites

Wadi¹,

Reinke²

2020

PLoS Pathog

104

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Microsporidia are obligate intracellular parasites that can infect a wide range of hosts. They cause death and disease in both humans and agriculturally important animals. They have also become a powerful model for understanding the evolution of intracellular parasites. Recent work has explored how microsporidia genomes have evolved, the evolutionary origins of microsporidia, and how microsporidia adapt to interact with their hosts.

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Section: Future Perspectivementioning

confidence: 99%

Evolution of microsporidia: An extremely successful group of eukaryotic intracellular parasites

Wadi¹,

Reinke²

2020

PLoS Pathog

104

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“…The importance of this metabolite was further demonstrated by injection of phosphatidic acid into flies, which resulted in increased parasite burden. This metabolite is thought to act as a precursor for membrane biosynthesis in the parasite; however, the mechanism by which microsporidia imports this host derived metabolite remains unknown (Franchet, Niehus, Caravello, & Ferrandon, 2019).…”

Section: Microsporidia Metabolismmentioning

confidence: 99%

The ins and outs of host‐microsporidia interactions during invasion, proliferation and exit

Jarkass

Reinke

2020

Cellular Microbiology

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Microsporidia are a large group of fungal-related obligate intracellular parasites. They are responsible for infections in humans as well as in agriculturally and environmentally important animals. Although microsporidia are abundant in nature, many of the molecular mechanisms employed during infection have remained enigmatic. In this review, we highlight recent work showing how microsporidia invade, proliferate and exit from host cells. During invasion, microsporidia use spore wall and polar tube proteins to interact with host receptors and adhere to the host cell surface. In turn, the host has multiple defence mechanisms to prevent and eliminate these infections. Microsporidia encode numerous transporters and steal host nutrients to facilitate proliferation within host cells. They also encode many secreted proteins which may modulate host metabolism and inhibit host cell defence mechanisms. Spores exit the host in a non-lytic manner that is dependent on host actin and endocytic recycling proteins. Together, this work provides a fuller picture of the mechanisms that these fascinating organisms use to infect their hosts.

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“…Similarly, infection of adult flies with the intracellular parasite Tubulinosema ratisbonensis leads to colonization of fat body cells and impairs triglyceride storage, directing host fatty acids to fuel parasite growth (Franchet et al, 2019). Lipid storage defects can be elicited by genetic activation of the Toll and Imd pathways, indicating that metabolic changes are dictated not only by pathogen interaction but also by signaling from the host immune system.…”

Section: Introductionmentioning

confidence: 99%

Innate immune signaling inDrosophilashifts anabolic lipid metabolism from triglyceride storage to phospholipid synthesis in an ER stress-dependent manner

Martínez

Bland

2020

Preprint

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During infection, cellular resources are allocated toward synthesis and secretion of effector proteins that neutralize and kill invading pathogens. In Drosophila, antimicrobial peptides (AMPs) are produced in the fat body, an organ that also serves as a major nutrient storage depot.Here we asked how the innate immune response activated by fat body Toll signaling alters lipid metabolism as a model for understanding how the cellular and energetic demands of the immune response are met. We find that genetic activation of fat body Toll signaling leads to a tissueautonomous reduction in triglyceride storage that is paralleled by decreased transcript levels of Lipin and midway, enzymes that carry out the final steps of triglyceride synthesis. In contrast, Kennedy pathway enzymes that synthesize phospholipids and their products, phosphatidylcholine and phosphatidylethanolamine, are induced in fat bodies with active Toll signaling. Induction of these enzymes depends on the unfolded protein response mediator Xbp1, and examination of endoplasmic reticulum (ER) morphology by transmission electron microscopy revealed significantly expanded ER in fat body cells with active Toll signaling.Together these results indicate that Toll signaling induces a metabolic switch from triglyceride storage to phospholipid synthesis and ER expansion; this occurs in response to AMP production and may sustain AMP synthesis and secretion during infection. Better understanding of how this anabolic switch in lipid metabolism is induced, as well as the long-term consequences of reduced triglyceride storage at the expense of phospholipid synthesis, should yield insight into metabolic diseases that stem from chronic inflammation.

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Phosphatidic acid as a limiting host metabolite for the proliferation of the microsporidium Tubulinosema ratisbonensis in Drosophila flies

Cited by 41 publications

References 51 publications

Evolution of microsporidia: An extremely successful group of eukaryotic intracellular parasites

Evolution of microsporidia: An extremely successful group of eukaryotic intracellular parasites

The ins and outs of host‐microsporidia interactions during invasion, proliferation and exit

Innate immune signaling inDrosophilashifts anabolic lipid metabolism from triglyceride storage to phospholipid synthesis in an ER stress-dependent manner

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