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

Hypusine in Plasmodium: a molecule determing the severity of malaria

Meeting Abstract

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  • Annette Kaiser - Institute for Pharmacogenetics, Medizinisches Forschungszentrum, Essen, Germany
  • David Kersting - Institute for Pharmacogenetics, Medizinisches Forschungszentrum, Essen, Germany
  • Mirco Krüger - Institute for Pharmacogenetics, Medizinisches Forschungszentrum, Essen, Germany

11th Malaria Meeting. Aachen, 08.-09.11.2013. Düsseldorf: German Medical Science GMS Publishing House; 2014. Doc13mal07

doi: 10.3205/13mal07, urn:nbn:de:0183-13mal076

Published: January 29, 2014

© 2014 Kaiser 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.



Hypusination in eukaryotic initiation factor 5A (EIF5A) is a unique posttranslational modification which so far has only been discovered in this protein. Hypusine was first isolated by Shiba et al. (1971) from brain cells and identified as a 4-amino-2-hydroxybutyl)lysine-derivative. This posttranslational modification is formed within two consecutive enzymatic steps i.e. deoxyhypusine synthase (DHS) and deoxyhypusine hydroxylase. Deoxyhypusine synthase transfers the aminobutyl moiety from the triamine spermidine to a specific lysine residue in EIF-5A while deoxyhypusine hydroxylase catalyzes hydroxylation in the side chain.

Over recent years we have identified both enzymes in the human malaria parasites P. falciparum and P. vivax. Both enzymes were evaluated as druggable targets [1]. Currently, investigations on the biological function of this unique posttranslational modification are performed. In recent experiments we showed that downregulation by silencing eiF-5A, dhs and dohh genes with shorthairpin RNAs leads to an impaired hypusine biosynthesis and to growth retardation of the parasite. Infection of NMRI mice with schizonts from the lethal P. berghei ANKA wildtype strain transgenic for plasmodial eIF-5A-specific shRNA or DHS-specific shRNA resulted in low parasitemia 2–9 days post infection before animals succumbed to hyperparasitemia similar to infections with the related but non-lethal phenotype P. berghei strain NK65. RT-PCR and Western blot experiments performed with blood from the transfected erythrocytic stages showed that both genes are important for the proliferation of the parasite. Moreover, these experiments clearly demonstrate that the hypusine pathway in Plasmodium is linked to human iNos induction .

Preliminary results of an in vivo knockdown show that eif-5A and dhs genes are essential for the proliferation of the parasite thus revisiting an old acquaintance for their importance in cell proliferation. This findings were even more supported in phenotyping experiments. To exclude any resistance association with the gene locus of eif-5A and dhs genes “knock in” experiments will be performed.


Atemnkeng VA, Pink M, Schmitz-Spanke S, Wu XJ, Dong LL, Zhao KH, May C, Laufer S, Langer B, Kaiser A. Deoxyhypusine hydroxylase from Plasmodium vivax, the neglected human malaria parasite: molecular cloning, expression and specific inhibition by the 5-LOX inhibitor zileuton. PLoS One. 2013;8(3):e58318. DOI: 10.1371/journal.pone.0058318 External link
Schwentke A, Krepstakies M, Mueller AK, Hammerschmidt-Kamper C, Motaal BA, Bernhard T, Hauber J, Kaiser A. In vitro and in vivo silencing of plasmodial dhs and eIf-5a genes in a putative, non-canonical RNAi-related pathway. BMC Microbiol. 2012 Jun 13;12:107. DOI: 10.1186/1471-2180-12-107 External link