Co-inhibition of Plasmodium falciparum
S-adenosylmethionine decarboxylase/ornithine
decarboxylase reveals perturbation-specific
compensatory mechanisms by transcriptome,
proteome and metabolome analyses

primary data clusters 
supplementary material  
figures and tables from manuscript  
and contributors  



Polyamines are ubiquitous components of all living cells and their depletion usually causes cytostasis, a strategy employed for treatment of West-African trypanosomiasis. To evaluate polyamine-depletion as an antimalarial strategy, cytostasis caused by the co-inhibition of S-adenosylmethionine decarboxylase/ornithine decarboxylase (PfAdoMetDC/ODC) in Plasmodium falciparum was studied with a comprehensive transcriptome, proteome and metabolome investigation. Highly synchronized cultures were sampled just before and during cytostasis and a novel zero time point definition was used to enable interpretation of results in lieu of the developmentally regulated control of gene expression in P. falciparum. Transcriptome analysis revealed the occurrence of a generalized transcriptional arrest just prior to the growth arrest due to polyamine-depletion. However, the abundance of 538 transcripts was differentially affected and included three perturbation-specific compensatory transcriptional responses: the increased abundance of the transcripts for lysine decarboxylase (LDC) and ornithine aminotransferase (OAT) as well as the decreased abundance of that for S-adenosylmethionine synthetase (AdoMet synthetase). Moreover, the latter two compensatory mechanisms were confirmed on both protein and metabolite levels confirming their biological relevance. In contrast with previous reports, the results provide evidence that P. falciparum respond to alleviate the detrimental effects of polyamine-depletion via regulation of its transcriptome and subsequently the proteome and metabolome.

[Home | Explore | Supplement | Download | Authors]
Last updated: 1 September 2008