Parasite Sensing of Host Nutrients and Environmental Cues

Zuzarte‐Luís, Vanessa; Mota, Maria M.

doi:10.1016/j.chom.2018.05.018

Cited by 74 publications

(63 citation statements)

References 116 publications

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“…For metabolic labeling experiments using [1][2][3][4][5][6][7][8][9][10][11][12][13] In order to assess dolichol and polyprenol profiles in trophozoite stage of the PfPPRD or PfCPT conditional knockdowns, parasites were grown in media supplemented either with 2.5 µg/mL Blasticidin S and 0.5 µM aTc, or only 2.5 µg/mL Blasticidin S for the indicated times ( Fig. 7 and 9).…”

Section: Stable Isotope Labeling Of P Falciparum-infected and Uninfementioning

confidence: 99%

Metabolomics profiling reveals new aspects of dolichol biosynthesis inPlasmodium falciparum

Zimbres¹,

Valenciano²,

Merino³

et al. 2019

Preprint

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The cis-polyisoprenoid lipids namely polyprenols, dolichols and their derivatives are linear polymers of several isoprene units. In eukaryotes, polyprenols and dolichols are synthesized as a mixture of four or more homologues of different length with one or two predominant species with sizes varying among organisms. Polyprenols have been hardly detectable in eukaryotic cells under normal conditions with the exception of plants and sporulating yeast. Our metabolomics studies revealed that cis-polyisoprenoids are more prevalent and diverse in the parasite Plasmodium falciparum than previously postulated as we uncovered active de novo biosynthesis and substantial levels of accumulation of polyprenols and dolichols of 15 to 19 isoprene units. A distinctive polyprenol and dolichol profile both within the intraerythrocytic asexual cycle and between asexual and gametocyte stages was also observed suggesting that cis-polyisoprenoid biosynthesis changes throughout parasite's development. In addition, we confirmed the presence of an active cisprenyltransferase (PfCPT) and that dolichol biosynthesis occurs via reduction of the polyprenol to dolichol by an active polyprenol reductase (PfPPRD) in the malaria parasite. Isotopic labeling and metabolomic analyses of a conditional mutant of PfCPT or PfPPRD suggest that polyprenols may be able to substitute dolichols in their biological functions when dolichol synthesis is impaired in Plasmodium.Malaria is caused by protozoan parasites of the genus Plasmodium and most cases of lifethreatening malaria are attributable to infection with Plasmodium falciparum. The parasite has a complex life cycle that involves the human host and its vector, the Anopheles mosquitoes. All clinical features are caused during the asexual intraerythrocytic life cycle due to the repeated invasion of human red blood cells (RBCs). The asexual intraerythrocytic developmental cycle of P. falciparum lasts around 48 h, during which the parasite progresses through four morphologically different stages: ring, trophozoite, and schizont stages, ending with rupture of the erythrocyte and release of merozoites that will invade new erythrocytes. Transmission of the malaria parasite requires development of male and female gametocytes (gametocytogenesis), which are ingested by female mosquitoes during a blood meal and undergo sexual reproduction in the mosquito's midgut. Nondividing P. falciparum gametocytes take between 10 and 12 2 days to fully mature and progress through five morphologically distinct forms (stages I to V), which are different from other Plasmodium species.During their complex life cycle malaria parasites encounter different nutritional environments within and between hosts. The presence of de novo and salvage pathways gives parasites a great metabolic flexibility to cope with those changes 1,2 . For example, mature RBCs are capable of only a few metabolic functions since transcription and translation is not present in these cells. However, a wide variety of metabolites are available to the parasite i...

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Section: Stable Isotope Labeling Of P Falciparum-infected and Uninfementioning

confidence: 99%

Metabolomics profiling reveals new aspects of dolichol biosynthesis inPlasmodium falciparum

Zimbres¹,

Valenciano²,

Merino³

et al. 2019

Preprint

View full text Add to dashboard Cite

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“…However, as is the case with many other intracellular pathogens, the intruder is not unnoticed, as evidenced by transcriptomic and metabolomic disturbances within the host. The latter uses these cues to counteract the infection on biochemical as well as immunological levels (for review, see 1 – 3 ).…”

Section: Introductionmentioning

confidence: 99%

Metabolic interactions between Toxoplasma gondii and its host

Blume

Seeber

2018

F1000Res

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Toxoplasma gondii is an obligate intracellular parasite belonging to the phylum Apicomplexa that infects all warm-blooded animals, including humans. T. gondii can replicate in every nucleated host cell by orchestrating metabolic interactions to derive crucial nutrients. In this review, we summarize the current status of known metabolic interactions of T. gondii with its host cell and discuss open questions and promising experimental approaches that will allow further dissection of the host–parasite interface and discovery of ways to efficiently target both tachyzoite and bradyzoite forms of T. gondii, which are associated with acute and chronic infection, respectively.

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“…Observed changes may be a direct result of infection or host manipulation, or simply a consequence of host damage during infection [1]. When examining the impacts of parasite infection, most studies focus on the pathological aspects of infection, which include a reduction in available nutrients due to parasite feeding [2], cytokine-driven sickness [3], injected or secreted toxins [4], physical tissue damage either directly from the parasite or indirectly via inflammation [5] and/or the redistribution of resources such as upregulation of the immune response [6]. The indirect, physical aspects of parasites are often not addressed, despite their conspicuous appearance as changes in host shape and size.…”

Section: Introductionmentioning

confidence: 99%

The cost of infection:Argulus foliaceusand its impact on the swimming performance of the three-spined stickleback (Gasterosteus aculeatus)

Stewart

Hunt

Mitchell

et al. 2018

J. R. Soc. Interface.

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For fish, there can be multiple consequences of parasitic infections, including the physical impacts on swimming and the pathological costs of infection. This study used the three-spined stickleback ( Gasterosteus aculeatus ) and the ectoparasitic fish louse, Argulus foliaceus , to assess both physical (including form drag and mass) and pathological effects of infection. Both sustained (prolonged swimming within an open channel flume) and burst (C-start) swimming performance were measured on individual fish before (trials 1–2) and after infection (trials 3–5). Experimental infection occurred shortly before the third trial, when the physical impacts of infection could be separated from any subsequent pathology as transmission of adult parasites causes instantaneous drag effects prior to observable pathology. Despite the relatively large size of the parasite and corresponding increase in hydrodynamic drag for the host, there were no observable physical effects of infection on either sustained or burst host swimming. By contrast, parasite-induced pathology is the most probable explanation for reduced swimming performance across both tests. All sticklebacks displayed a preference for flow refugia, swimming in low-velocity regions of the flume, and this preference increased with both flow rate and infection time. This study suggests that even with large, physically demanding parasites their induced pathology is of greater concern than direct physical impact.

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Parasite Sensing of Host Nutrients and Environmental Cues

Cited by 74 publications

References 116 publications

Metabolomics profiling reveals new aspects of dolichol biosynthesis inPlasmodium falciparum

Metabolomics profiling reveals new aspects of dolichol biosynthesis inPlasmodium falciparum

Metabolic interactions between Toxoplasma gondii and its host

The cost of infection:Argulus foliaceusand its impact on the swimming performance of the three-spined stickleback (Gasterosteus aculeatus)

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