Strand specific RNA sequencing of Plasmodium falciparum clinical isolates

The malaria parasite is reported to show distinct gene regulation patterns in response to its host microenvironment. In this study, we analyse gene expression across clinical isolates of Plasmodium falciparum associated with two distinct clinical manifestations: hepatic dysfunction and cerebral malaria, and compare their transcriptomic profile with parasite isolates showing uncomplicated malaria manifestations. Our data profiles disease-specific gene expression of both sense and Natural Antisense Transcripts (NATs) from the nucleus, mitochondria and apicoplast genomes. Strand-specific pooled RNA sequencing has detected approximately 90% of genes expressing both transcript types, with distinct variability between disease manifestations. Identification of NATs complementary to rRNA species indicate an important regulatory layer crucial for rRNA stability in the parasites. We have also identified novel associations between increased mitochondrial respiration and disease severity - potentially contributing to the more aggressive pathology of cerebral malaria. Our data catalogues the expression profile of both sense and NATs across all the three multigene families – var, stevor and rifins – known to contribute to parasite virulence in the host. These findings elaborate on how parasites adapt to the host environment in severe malaria and pave the way for disease-specific, informed antimalarials.