Joly, D. | Search bioRxiv

bioRxiv2023

Host metabolic pathways essential for malaria and related hemoparasites in the infection of nucleated cells

Apicomplexan parasite diseases, including malaria (Plasmodium) and theileriosis (Theileria), pose a significant threat to global health and the socioeconomic well-being of low-income countries. Despite recent advances, the common host metabolic proteins essential for these highly auxotrophic pathogens remain elusive. Here, we present a comprehensive investigation integrating a metabolic model of P. falciparum parasites in hepatocytes and a genome-wide CRISPR screen targeting Theileria schizont-infected macrophages. We reveal unifying host metabolic enzymes critical for the intracellular survival of these related hematozoa. We show that pathways such as host purine and heme biosynthesis are essential for both Theileria survival and Plasmodium liver development, while genes involved in glutathione and polyamine biosynthesis are predicted to be essential for Plasmodium only under certain metabolic conditions. Our work highlights the importance of host porphyrins for the viability of liver-stage Plasmodium. Shared parasite vulnerabilities provide a resource for exploring alternative therapeutic approaches to combat these crippling diseases.

microbiology↗

bioRxiv2019

Chromatin structure changes in Daphnia populations upon exposure to environmental cues - or - The discovery of Wolterecks \"Matrix\"

Phenotypic plasticity is an important feature of biological systems that is likely to play a major role in the future adaptation of organisms to the ongoing global changes. It may allow an organism to produce alternative phenotypes in responses to environmental cues. Modifications in the phenotype can be reversible but are sometimes enduring and can even span over generations. The notion of phenotypic plasticity was conceptualized in the early 20th century by Richard Woltereck. He introduced the idea that the combined relations of a phenotypic character and all environmental gradients that influence on it can be defined as \"norm of reaction\". Norms of reaction are specific to species and to lineages within species, and they are heritable. He postulated that reaction norms can progressively be shifted over generations depending on the environmental conditions. One of his biological models was the water-flee daphnia. Woltereck proposed that enduring phenotypic modifications and gene mutations could have similar adaptive effects, and he postulated that their molecular bases would be different. Mutations occurred in genes, while enduring modifications were based on something he called the Matrix. He suggested that this matrix (i) was associated with the chromosomes, (ii) that it was heritable, (iii) it changed during development of the organisms, and (iv) that changes of the matrix could be simple chemical substitutions of an unknown, but probably polymeric molecule. We reasoned that the chromatin has all postulated features of this matrix and revisited Wolterecks classical experiments with daphnia. We developed a robust and rapid ATAC-seq technique that allows for analyzing chromatin of individual daphnia and show here (i) that this technique can be used with minimal expertise in molecular biology, and (ii) we used it to identify open chromatin structure in daphnia exposed to different environmental cues. Our result indicates that chromatin structure changes consistently in daphnia upon this exposure confirming Wolterecks classical postulate.

evolutionary biology↗