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Ambient glucose concentration and gene expression in Plasmodium falciparum

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      This opened a debate [6] that was settled by recent studies unambiguously showing that malaria parasites can produce directed transcriptional responses when exposed to some specific external conditions. Here, we will describe only three well-defined examples of directed transcriptional responses (Figure 1), but many other studies have reported transcriptional changes after exposing parasites to different stress conditions, such as restriction of specific nutrients or exposure to drugs [30–35]. However, in many cases, the transcriptional changes occurred in genes involved in processes unrelated to protection from the stress condition and it was impossible to distinguish between authentic transcriptional responses and changes in transcript levels attributable to parasite death or growth arrest.

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      GR is a metabolic stress that has been studied in other protists and, in some cases, is associated with pathogenesis. For instance, PfEMP (var) genes, key molecules in malaria pathogenesis, are upregulated upon GR [13]. Additionally, GR induces the differentiation of trophozoites into cysts in Entamoeba invadens [14] and boosts Entamoeba histolytica virulence [15,16].

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      A large proportion of regulated genes belonged to large gene families encoding exported proteins and surface antigens. The bulk regulation of genes belonging to large, co-expressed, multi-membered gene families has also been a feature of transcriptional responses of Plasmodium to a number of other stimuli (Clark et al. 2008; Fang et al. 2004) and is likely to represent a general rather than drug-specific response. We observed such a response in Plasmodium upon treatment of parasites with the apicoplast inhibitor thiostrepton (Tarr et al. 2011).

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