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bioRxiv · 10.1101/2021.03.09.434570

The extracellular milieu of Toxoplasma-s lytic cycle drives lab-adaptation and promotes changes in lipid metabolism primarily driven by transcriptional reprogramming

Primo, V. A.·Rezvani, Y.·Farrell, A.·Vajdi Hoojghan, A.·Marth, G. T.·Zarringhalam, K.·Gubbels, M.-J.
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Abstract

To map host-independent in vitro virulence traits of Toxoplasma gondii, evolve and resequencing (E&R) during the lab-adaption was applied. Phenotypic assessments of the lytic cycle revealed that only traits needed in the extracellular milieu evolved. Surprisingly, only non-synonymous mutations in a P4 flippase fixed in two populations. However, dramatic changes in the transcriptional signature of extracellular parasites revealed a "pro-tachyzoite" profile as well as upregulation of fatty acid biosynthesis (FASII) pathway genes. More general, a set of 300 genes which expression profile changes during evolution mapped to specific traits. Validation of a select number of genes in this set by knock-outs indeed confirmed their role in lab-adaptation. Finally, assembly of an ApiAP2 and Myb transcription factor network revealed the transcriptional program underlying the adapting extracellular state. Overall, E&R is a new genomic tool successfully applied to map the development of polygenic traits underlying in vitro virulence of T. gondii.

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Primo, V. A., Rezvani, Y., Farrell, A., Vajdi Hoojghan, A., Marth, G. T., Zarringhalam, K., Gubbels, M.-J.. 2021-03-09. The extracellular milieu of Toxoplasma-s lytic cycle drives lab-adaptation and promotes changes in lipid metabolism primarily driven by transcriptional reprogramming. https://doi.org/10.1101/2021.03.09.434570

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