Changes in the transcriptome of the malaria parasite Plasmodium falciparumduring the initial phase of transmission from the human to the mosquito

Abstract

BackgroundThe transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by dormant sexual precursor cells, the gametocytes, which become activated in the mosquito midgut. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they play a crucial role in spreading the tropical disease. The human-to-mosquito transmission triggers important molecular changes in the gametocytes, which initiate gametogenesis and prepare the parasite for life-cycle progression in the insect vector.ResultsTo better understand gene regulations during the initial phase of malaria parasite transmission, we focused on the transcriptome changes that occur within the first half hour of parasite development in the mosquito. Comparison of mRNA levels of P. falciparum gametocytes before and 30 min following activation using suppression subtractive hybridization (SSH) identified 126 genes, which changed in expression during gametogenesis. Among these, 17.5% had putative functions in signaling, 14.3% were assigned to cell cycle and gene expression, 8.7% were linked to the cytoskeleton or inner membrane complex, 7.9% were involved in proteostasis and 6.4% in metabolism, 12.7% were cell surface-associated proteins, 11.9% were assigned to other functions, and 20.6% represented genes of unknown function. For 40% of the identified genes there has as yet not been any protein evidence.For a subset of 27 genes, transcript changes during gametogenesis were studied in detail by real-time RT-PCR. Of these, 22 genes were expressed in gametocytes, and for 15 genes transcript expression in gametocytes was increased compared to asexual blood stage parasites. Transcript levels of seven genes were particularly high in activated gametocytes, pointing at functions downstream of gametocyte transmission to the mosquito. For selected genes, a regulated expression during gametogenesis was confirmed on the protein level, using quantitative confocal microscopy.ConclusionsThe obtained transcriptome data demonstrate the regulations of gene expression immediately following malaria parasite transmission to the mosquito. Our findings support the identification of proteins important for sexual reproduction and further development of the mosquito midgut stages and provide insights into the genetic basis of the rapid adaption of Plasmodium to the insect vector.

Translational repression of the cpw-wpc gene family in the malaria parasite Plasmodium

“…However, transcripts of the cpw-wpc genes PF3D7_1234700, PF3D7_1429300, PF3D7_0630000 and PF3D7_1331400 are downregulated in stage V PfPuf2 knockout gametocytes, indicating that some other mode of translational repression is likely to regulate these genes. Ngwa et al [62] [17,18].…”

Lysine Acetylation in Sexual Stage Malaria Parasites Is a Target for Antimalarial Small Molecules

“…Recent work has also identified the P. falciparum gametocyte development 1 (Pfgdv1) gene as being critical for gametocyte production (24). In addition, transcriptomic data demonstrate significant changes in a subset of genes immediately following malaria parasite transmission to the mosquito (17).…”

“…This suggests that mature gametocytes do turn on the different proteins and pathways needed for rapid development into gametes. During gametocytogenesis and transmission, P. falciparum parasites express new sets of genes and proteins likely to be important for sexual development, survival, and reproduction in the mosquito vector (12)(13)(14)(15)(16)(17)(18)(19). For example, gametocyte maturation and gametocytogenesis are accompanied by the coordinated expression of adhesive proteins, such as the epidermal growth factor domain-containing proteins P. falciparum s25 (Pfs25) and P. falciparum s28 (Pfs28), the 6-Cys proteins P. falciparum s230 (Pfs230) and P. falciparum s48/45 (Pfs48/45), and the LCCL domain-containing P. falciparum CCp (PfCCp) proteins (20)(21)(22)(23).…”

Protein phosphorylation during Plasmodium berghei gametogenesis

“…In the vertebrate, gamete-precursor parasite stages (gametocytes) develop and are transferred to the mosquito midgut with the bloodmeal when females feed on infected vertebrates. Gametocytes rapidly exit erythrocytes and transform into gametes; male gametocytes undergo three rounds of genome replication and mitotic division, resulting in the release of eight highly-motile flagellated microgametes, whereas female gametocytes differentiate into macrogametes (Kuehn and Pradel, 2010; Ngwa et al, 2013). Gametes fertilize and give rise to zygotes that transform into motile ookinetes, which actively penetrate the mosquito midgut epithelium and develop into oocysts.…”