Abstract
BackgroundMicroarray studies using in vitro cultures of synchronized, blood-stage Plasmodium falciparum malaria parasites have revealed a ‘just-in-time’ cascade of gene expression with some indication that these transcriptional patterns remain stable even in the presence of external stressors. However, direct analysis of transcription in P. falciparum blood-stage parasites obtained from the blood of infected patients suggests that parasite gene expression may be modulated by factors present in the in vivo environment of the host. The aim of this study was to examine changes in gene expression of the rodent malaria parasite, Plasmodium yoelii 17X, while varying the in vivo setting of replication.MethodsUsing P. yoelii 17X parasites replicating in vivo, differential gene expression in parasites isolated from individual mice, from independent infections, during ascending, peak and descending parasitaemia and in the presence and absence of host antibody responses was examined using P. yoelii DNA microarrays. A genome-wide analysis to identify coordinated changes in groups of genes associated with specific biological pathways was a primary focus, although an analysis of the expression patterns of two multi-gene families in P. yoelii, the yir and pyst-a families, was also completed.ResultsAcross experimental conditions, transcription was surprisingly stable with little evidence for distinct transcriptional states or for consistent changes in specific pathways. Differential gene expression was greatest when comparing differences due to parasite load and/or host cell availability. However, the number of differentially expressed genes was generally low. Of genes that were differentially expressed, many involved biologically diverse pathways. There was little to no differential expression of members of the yir and pyst-a multigene families that encode polymorphic proteins associated with the membrane of infected erythrocytes. However, a relatively large number of these genes were expressed during blood-stage infection regardless of experimental condition.ConclusionsTaken together, these results indicate that 1) P. yoelii gene expression remains stable in the presence of a changing host environment, and 2) concurrent expression of a large number of the polymorphic yir and pyst-a genes, rather than differential expression in response to specific host factors, may in itself limit the effectiveness of host immune responses.
Highlights
Microarray studies using in vitro cultures of synchronized, blood-stage Plasmodium falciparum malaria parasites have revealed a ‘just-in-time’ cascade of gene expression with some indication that these transcriptional patterns remain stable even in the presence of external stressors
Little variation in gene expression in Plasmodium yoelii 17X blood-stage parasites obtained from individual mice challenged with the same inoculum of infected red blood cell (iRBC) In the P. yoelii 17X model, peak parasitaemia generally occurs on day 14–16, reaching parasitaemias of 40-45% in BALB/c mice
As a starting point in evaluating variability in gene expression in blood-stage parasites replicating in vivo in different hosts, three mice were simultaneously infected with 1x105 P. yoelii 17X iRBCs from a single donor mouse
Summary
Microarray studies using in vitro cultures of synchronized, blood-stage Plasmodium falciparum malaria parasites have revealed a ‘just-in-time’ cascade of gene expression with some indication that these transcriptional patterns remain stable even in the presence of external stressors. Most genes are expressed only once during the asexual cycle and groups of genes involved in similar processes are active at the same time [4,5] This highly coordinated expression profile implies tightly controlled regulation, as relatively few transcription factors have been identified in Plasmodium, precisely how gene regulation occurs remains incompletely understood. In these transcriptional studies, in vitro cultured P. falciparum parasites were tightly synchronized to evaluate gene expression at distinct points during the life cycle, and growth conditions were controlled to avoid introducing unwanted stressors and other confounding factors
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