@article{NgwaScheuermayerMairetal.2013,
  author    = {Ngwa, Che Julius and Scheuermayer, Matthias and Mair, Gunnar Rudolf and Kern, Selina and Br{\"u}gl, Thomas and Wirth, Christine Clara and Aminake, Makoah Nigel and Wiesner, Jochen and Fischer, Rainer and Vilcinskas, Andreas and Pradel, Gabriele},
  title     = {Changes in the transcriptome of the malaria parasite Plasmodium falciparum during the initial phase of transmission from the human to the mosquito},
  series = {BMC Genomics},
  volume    = {14},
  journal   = {BMC Genomics},
  number    = {256},
  issn      = {1471-2164},
  doi       = {10.1186/1471-2164-14-256},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121905},
  year      = {2013},
  abstract  = {Background: The 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. Results: To 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. Conclusions: The 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.},
  language  = {en}
}
@article{WirthGlushakovaScheuermayeretal.2014,
  author    = {Wirth, Christine C. and Glushakova, Svetlana and Scheuermayer, Matthias and Repnik, Urska and Garg, Swatl and Schaack, Dominik and Kachman, Marika M. and Weißbach, Tim and Zimmerberg, Joshua and Dandekar, Thomas and Griffiths, Gareth and Chitnis, Chetan E. and Singh, Shallja and Fischer, Rainer and Pradel, Gabriele},
  title     = {Perforin-like protein PPLP2 permeabilizes the red blood cell membrane during egress of Plasmodium falciparum gametocytes},
  series = {Cellular Microbiology},
  volume    = {16},
  journal   = {Cellular Microbiology},
  number    = {5},
  doi       = {10.1111/cmi.12288},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120895},
  pages     = {709-33},
  year      = {2014},
  abstract  = {Egress of malaria parasites from the host cell requires the concerted rupture of its enveloping membranes. Hence, we investigated the role of the plasmodial perforin-like protein PPLP2 in the egress of Plasmodium falciparum from erythrocytes. PPLP2 is expressed in blood stage schizonts and mature gametocytes. The protein localizes in vesicular structures, which in activated gametocytes discharge PPLP2 in a calcium-dependent manner. PPLP2 comprises a MACPF domain and recombinant PPLP2 has haemolytic activities towards erythrocytes. PPLP2-deficient [PPLP2(-)] merozoites show normal egress dynamics during the erythrocytic replication cycle, but activated PPLP2(-) gametocytes were unable to leave erythrocytes and stayed trapped within these cells. While the parasitophorous vacuole membrane ruptured normally, the activated PPLP2(-) gametocytes were unable to permeabilize the erythrocyte membrane and to release the erythrocyte cytoplasm. In consequence, transmission of PPLP2(-) parasites to the Anopheles vector was reduced. Pore-forming equinatoxin II rescued both PPLP2(-) gametocyte exflagellation and parasite transmission. The pore sealant Tetronic 90R4, on the other hand, caused trapping of activated wild-type gametocytes within the enveloping erythrocytes, thus mimicking the PPLP2(-) loss-of-function phenotype. We propose that the haemolytic activity of PPLP2 is essential for gametocyte egress due to permeabilization of the erythrocyte membrane and depletion of the erythrocyte cytoplasm.},
  language  = {en}
}