gms | German Medical Science

11th Malaria Meeting

Malaria Group / Section Antiparasitic Chemotherapy of the Paul-Ehrlich-Society (PEG e. V.) in cooperation with the German Society for Tropical Medicine and International Health (DTG e. V.) and the German Society for Parasitology (DGP e. V.)

08.11. - 09.11.2013, Aachen

Effect of DPAP-specific inhibitors on gametogenesis in Plasmodium falciparum

Meeting Abstract

  • Tim Weißbach - Institute for Molecular Biotechnology, RWTH Aachen University, Aachen, Germany
  • Ludmilla Sologub - Research Center for Infectious Diseases, University of Würzburg, Würzburg, Germany
  • Rainer Fischer - Institute for Molecular Biotechnology, RWTH Aachen University, Aachen, Germany
  • Gabriele Pradel - Institute for Molecular Biotechnology, RWTH Aachen University, Aachen, Germany

11th Malaria Meeting. Aachen, 08.-09.11.2013. Düsseldorf: German Medical Science GMS Publishing House; 2014. Doc13mal20

doi: 10.3205/13mal20, urn:nbn:de:0183-13mal208

Published: January 29, 2014

© 2014 Weißbach et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



The transmission of the malaria parasite Plasmodium falciparum from humans to mosquitoes is mediated by sexual precursor cells, the intraerythrocytic gametocytes, which become activated in the mosquito midgut by environmental stimuli and then undergo gametogenesis. Egress of the gametocytes from the enveloping erythrocyte is a crucial step for the parasites to prepare for fertilization, but the molecular mechanisms of gametocyte egress are not well understood. Previous studies indicated that plasmodial proteases are involved in this process [1], [2], but these proteases have not yet been identified. A new study showed that inhibition of the dipeptidyl aminopeptidases PfDPAP1 and PfDPAP3 resulted in blocked transmission of P. falciparum to the mosquito [3]. We now aimed to investigate, if the DPAPs play a role in gametocyte egress. We studied the effect of two DPAP-specific inhibitors (ML4118S and JCP410) on gametogenesis via exflagellation inhibition assay and electron microscopy. Both inhibitors were able to completely inhibit gametogenesis by impairing the rupture of the parasitophorous vacuole membrane. Noteworthy, while the asexual replication cycle DPAP3 activates the subtilisin-like protease PfSUB1, which in consequence processes the egress molecule PfSERA5 [4] these two proteins cannot be detected in gametocytes via immunofluorescence assays. Our data indicate that plasmodial DPAPs mediate the egress of the gametocytes from the enveloping erythrocyte in a PfSUB1/PfSERA5-independent pathway.


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