The cytosolic glyoxalases of Plasmodium falciparum are dispensable during asexual blood-stage development
Authors:Cletus A. Wezena1, Romy Alisch1, Alexandra Golzmann2, Linda Liedgens1, Verena Staudacher1,3, Gabriele Pradel2 and Marcel Deponte1,3
doi: 10.15698/mic2018.01.608
Volume 5, pp. 32 to 41, published 20/11/2017.
1 Department of Parasitology, Ruprecht-Karls University, D-69120 Heidelberg, Germany.
2 Division of Cellular and Applied Infection Biology, Institute of Zoology, RWTH Aachen University, D-52074 Aachen, Germany.
3 Department of Chemistry/Biochemistry, University of Kaiserslautern, D-67663 Kaiserslautern, Germany.
Keywords:
Plasmodium falciparum, malaria, glyoxalase, drug target, CRISPR/Cas9
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
Cletus A. Wezena, Romy Alisch, Alexandra Golzmann, Linda Liedgens, Verena Staudacher, Gabriele Pradel and Marcel Deponte (2017). The cytosolic glyoxalases of Plasmodium falciparum are dispensable during asexual blood-stage development. Microbial Cell: 5(1): 32-41. doi: 10.15698/mic2018.01.608
© 2017 Wezena et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
The enzymes glyoxalase 1 and 2 (Glo1 and Glo2) are found in most eukaryotes and catalyze the glutathione-dependent conversion of 2-oxoaldehydes to 2-hydroxycarboxylic acids. Four glyoxalases are encoded in the genome of the malaria parasite Plasmodium falciparum, the cytosolic enzymes PfGlo1 and PfcGlo2, the apicoplast enzyme PftGlo2, and an inactive Glo1-like protein that also carries an apicoplast-targeting sequence. Inhibition or knockout of the Plasmodium glyoxalases was hypothesized to lead to an accumulation of 2-oxoaldehydes and advanced glycation end-products (AGE) in the host-parasite unit and to result in parasite death. Here, we generated clonal P. falciparum strain 3D7 knockout lines for PFGLO1 and PFcGLO2 using the CRISPR-Cas9 system. Although 3D7Δglo1 knockout clones had an increased susceptibility to external glyoxal, all 3D7Δglo1 and 3D7Δcglo2 knockout lines were viable and showed no significant growth phenotype under standard growth conditions. Furthermore, the lack of PfcGlo2, but not PfGlo1, increased gametocyte commitment in the knockout lines. In summary, PfGlo1 and PfcGlo2 are dispensable during asexual blood-stage development while the loss of PfcGlo2 may induce the formation of transmissible gametocytes. These combined data show that PfGlo1 and PfcGlo2 are most likely not suited as targets for selective drug development.