RNA-seq Analysis of Plasmodium falciparum Shows Upregulated Genes Involved in Merozoite Egress and Erythrocyte Invasion

Abstract

Malaria is a febrile disease caused by parasites of the genus Plasmodium. The most severe cases and most of the deaths of malaria are due to Plasmodium falciparum infection. Investigating transcriptional differences in P. falciparum between severe and uncomplicated cases can shed light on malaria pathogenicity and virulence. In this study we used previously acquired publicly available RNA sequencing data from severe and uncomplicated cases of P. falciparum infection. Differential expression analysis of the P. falciparum transcriptome showed that a group of gene products involved in merozoite egress and erythrocyte invasion were significantly upregulated in severe malaria. More specifically, we identified that Subtilisin-like protease 1 (SUB1), merozoite surface proteins 1 and 2 (MSP1 and MSP2), and serine repeat antigen 5 (SERA5) were upregulated in severe malaria. Upregulation of genes in merozoite egress and erythrocyte invasion suggest molecular mechanisms of malaria severity specifically during the blood stages. In addition, upregulation of tyrosine kinase-like protein (TKL) transcription in conjunction with SERA5 regulatory proteins upregulation suggests additional mechanisms of SERA5-mediated malaria severity.