Metabolomic and Transcriptomic rewiring between virus resistance and susceptibility in Ostreococcus mediterraneus

The genus Ostreococcus, comprising picoeukaryotic unicellular algae, plays a key role in many coastal marine ecosystems. These phytoplankton are infected by lytic double-stranded DNA prasinoviruses against whom they have the capacity to reliably evolve stable antiviral resistance. Regulation of virus resistance and susceptibility is hypothesized to arise through a phenotypic switch, as resistant cell lines can be isolated from susceptible lines after viral exposure and vice versa. To elucidate the molecular mechanisms underlying this resistance, we integrated untargeted metabolomic analyses and transcriptomics in virus-resistant and virus-susceptible lines of O. mediterraneus. Transcriptomic analyses corroborated previous findings in O. tauri, revealing that most gene expression changes were concentrated on a single chromosome. Specifically, a ~530 kb region was over-transcribed in virus-resistant lines, while a distinct ~110 kb region was over-expressed in virus-susceptible lines. Comparative metabolomics identified several oxidized galactolipids and oxidized sterols as biomarkers of the susceptible phenotype, while fewer biomarkers were identified for the resistant phenotype. By integrating transcriptomic and metabolomic signatures, focusing on the expression of genes within biosynthetic pathways linked to these metabolite biomarkers, we uncovered candidate molecular mechanisms underlying the cellular physiology of susceptible versus resistant phenotypes.