Sylke Müller, Christian Doerig
The life cycle of malaria parasites comprises a complex succession of developmental stages occurring in two different hosts, the human patient and the mosquito vector. In both hosts, the parasite encounters hostile environments and must deal with stresses such as immune responses, sharp temperature shifts and exposure to drugs; partly because of large-scale haemoglobin degradation in the infected erythrocyte and resulting haeme release, oxidative stress is another challenge that the parasite must face. In contrast to other eukaryotes where stress response is largely mediated through a well-defined and robust transcriptional response, it appears that malaria parasites opted for a different strategy. In line with the largely fixed transcriptional programme that characterises the progression of the organisms through their life cycle stages, the transcriptional response to several stresses (such as drug treatments) consists primarily of low-amplitude, genome-wide changes of transcript abundance. However, recent findings suggest that specific transcriptome adaptations, that affect selected aspects of the parasites' physiology, also occur. Overall, the absence in the parasite's kinome of classical stress response mediators such as SAPKs/JNKs, together with the relative scarcity in transcription factors, suggest a low level of flexibility of the parasite in implementing classical eukaryotic stress response pathways. Post-transcriptional mechanisms are expected to play crucial roles in stress response in Plasmodium as exemplified by the demonstrated involvement of an eIF2alpha kinases in response to starvation stress.
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