Back

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.

2021-03-09 microbiology
10.1101/2021.03.09.434570 bioRxiv
Show 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.

Matching journals

The top 1 journal accounts for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.