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

BACKGROUND: 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. This species remains enigmatic due to the inability to maintain it in long-term culture, the low parasitemia observed in human infections, and its frequent co-infection with other malaria species. METHODOLOGY/PRINCIPAL FINDINGS: 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 identified 3,699 expressed genes, of which 263 are developmentally regulated and 309 are P. malariae-specific, including genes with unknown functions and without orthologs in other Plasmodium spp. We detected unique expression patterns of the ApiAP2 family of transcription factors, many of which appear to function as master regulators during sporogony. Several members of multigene families, such as PIR, PHIST, and fam-l, were found to be expressed, and new families potentially showing transcriptional heterogeneity were described. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that the P. malariae transcriptome is largely conserved; however, a distinct set of expressed genes lacking detectable orthologs may contribute to differences in transmission and virulence. Given the scarcity of genomic and transcriptomic data for this pathogen and considering the global distribution of P. malariae and its potential role in sustaining malaria transmission, this study has direct implications for malaria control and elimination efforts.