The mosquito-stage transcriptome of the neglected malaria parasite Plasmodium malariae reveals species-specific gene expression signatures and functional adaptations

Abstract

ABSTRACT To survive and multiply in different host niches, malaria parasites require sets of proteins that are expressed during the life cycle in a timely manner. Plasmodium malariae is a human malaria parasite that is present in most malaria-endemic regions. However, this species remains enigmatic because it is very challenging to culture, its low parasitaemia in human infections, and frequent co-infection with other malarias. We investigate the transcriptome of P. malariae during transmission in the vector by analyzing RNA-seq data from midgut and salivary gland parasite stages obtained in two experimental mosquito infections with field P. malariae isolates. Our analysis resulted in 3,699 expressed genes, of which 263 are developmentally regulated and 1,338 are P. malariae specific, including genes with unknown functions and without orthologs in other Plasmodium . We detected unique expression patterns of the ApiAP2 family of transcription factors, many of which appear to function as master regulators during sporogony. We found expressed several members of multigene families, like PIR, PHIST, fam-l, and described new families potentially showing transcriptional heterogeneity. Our findings point to the uniqueness of the P. malariae transcriptome, probably related to different transmission traits in the vector, and the lower pathogenicity and virulence in the human.