The Plasmodium falciparum sexual development transcriptome: A microarray analysis using ontology-based pattern identification

Young, Jason A.; Fivelman, Quinton L.; Blair, Peter L.; Vega, Patricia de la; Roch, Karine G. Le; Zhou, Yingyao; Carucci, Daniel J.; Baker, David A.; Winzeler, Elizabeth A.

doi:10.1016/j.molbiopara.2005.05.007

Cited by 311 publications

(353 citation statements)

References 68 publications

Supporting

Mentioning

336

Contrasting

Order By: Relevance

“…Because there are no available measurements for the unidentified form of sexually committed rings (29), we use the expression profiles of early stage gametocytes as a proxy for committed gametocytes, ẑ g . The most complete expression profile of early gametocyte stages without contaminants from asexual stages is day 4 of the gametocyte time course obtained by Young et al (20). We note that the days of the Young et al time course consisting of 100% gametocytes (days 4 -12) are highly correlated, and results vary little using different sexual reference strains.…”

Section: Microscopymentioning

confidence: 57%

“…We note that because the relative mRNA expression of sexual and asexual cells is unknown, the estimate of ␣ corresponds to total fraction of mRNA rather than a true proportion of sexual cells. To validate this model, we applied it to 3 reference time courses from Young et al (20), which represent a mixture of sexual and asexual stages in proportions subsequently measured by light and fluorescence microscopy. In all 3 cases, the model yielded estimates of gametocyte mRNA fraction, ␣, which were highly correlated with the measured percentage of gametocytes in the culture (Fig.…”

Section: Analysis Of Published In Vivo Expression Profilesmentioning

confidence: 99%

“…S7 D-G). As a control, in vitro asexual stages (6,17) and in vitro gametocytes (20) are plotted in the same space. The estimated fraction of the culture developing sexually is strongly associated with cluster membership from the Daily et al (2) study (F test, P Ͻ 0.0001).…”

Section: Analysis Of Published In Vivo Expression Profilesmentioning

confidence: 99%

See 2 more Smart Citations

Statistical estimation of cell-cycle progression and lineage commitment in Plasmodium falciparum reveals a homogeneous pattern of transcription in ex vivo culture

Lemieux

Gomez-Escobar

Feller

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

135

View full text Add to dashboard Cite

We have cultured Plasmodium falciparum directly from the blood of infected individuals to examine patterns of mature-stage gene expression in patient isolates. Analysis of the transcriptome of P. falciparum is complicated by the highly periodic nature of gene expression because small variations in the stage of parasite development between samples can lead to an apparent difference in gene expression values. To address this issue, we have developed statistical likelihood-based methods to estimate cell cycle progression and commitment to asexual or sexual development lineages in our samples based on microscopy and gene expression patterns. In cases subsequently matched for temporal development, we find that transcriptional patterns in ex vivo culture display little variation across patients with diverse clinical profiles and closely resemble transcriptional profiles that occur in vitro. These statistical methods, available to the research community, assist in the design and interpretation of P. falciparum expression profiling experiments where it is difficult to separate true differential expression from cell-cycle dependent expression. We reanalyze an existing dataset of in vivo patient expression profiles and conclude that previously observed discrete variation is consistent with the commitment of a varying proportion of the parasite population to the sexual development lineage. malaria ͉ microarray

show abstract

Section: Microscopymentioning

confidence: 57%

Section: Analysis Of Published In Vivo Expression Profilesmentioning

confidence: 99%

See 1 more Smart Citation

Statistical estimation of cell-cycle progression and lineage commitment in Plasmodium falciparum reveals a homogeneous pattern of transcription in ex vivo culture

Lemieux

Gomez-Escobar

Feller

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

135

View full text Add to dashboard Cite

show abstract

“…The genome of P . falciparum encodes for four putative cyclic nucleotide PDEs, PDEα‐δ (Young et al ., 2005). Chemical inhibition of PDE activity stimulates rounding up of mature gametocytes in the absence of XA, thereby verifying that increased cGMP‐levels trigger gametogenesis (McRobert et al ., 2008) (Fig.…”

Section: The Initiation Of Gametogenesismentioning

confidence: 99%

The development of malaria parasites in the mosquito midgut

Bennink

Kiesow

Pradel

2016

Cellular Microbiology

167

155

View full text Add to dashboard Cite

SummaryThe mosquito midgut stages of malaria parasites are crucial for establishing an infection in the insect vector and to thus ensure further spread of the pathogen. Parasite development in the midgut starts with the activation of the intraerythrocytic gametocytes immediately after take‐up and ends with traversal of the midgut epithelium by the invasive ookinetes less than 24 h later. During this time period, the plasmodia undergo two processes of stage conversion, from gametocytes to gametes and from zygotes to ookinetes, both accompanied by dramatic morphological changes. Further, gamete formation requires parasite egress from the enveloping erythrocytes, rendering them vulnerable to the aggressive factors of the insect gut, like components of the human blood meal. The mosquito midgut stages of malaria parasites are unprecedented objects to study a variety of cell biological aspects, including signal perception, cell conversion, parasite/host co‐adaptation and immune evasion. This review highlights recent insights into the molecules involved in gametocyte activation and gamete formation as well as in zygote‐to‐ookinete conversion and ookinete midgut exit; it further discusses factors that can harm the extracellular midgut stages as well as the measures of the parasites to protect themselves from any damage.

show abstract

“…This includes differentiation of gametes into ookinetes, invasion of the mid-gut epithelium, oocyst formation, and, ultimately, differentiation into sporozoites [77,78]. The increased reliance on the TCA is supported by upregulation of TCA enzymes in gametocyte stages [79,80] and the profound physiological consequences of genetic disruption and/or chemical inhibition of these enzymes (Figure 1) [26,31,36,43,44,46,51,62,81].…”

Section: Mitochondrial Metabolism Across the Alveolatamentioning

confidence: 99%

Apicomplexan Energy Metabolism: Carbon Source Promiscuity and the Quiescence Hyperbole

Jacot

Waller

Soldati‐Favre

et al. 2016

Trends in Parasitology

View full text Add to dashboard Cite

Pages 15apicomplexan mitochondrion in energy generation has remained unclear, given the glucosereplete intracellular nature of the environmental niches of these parasites and the apparent reduction of mitochondrial metabolic pathways [4][5][6][7]. For example, apicomplexan mitochondria lack 'type I' NADH dehydrogenase (NDH, complex I of the ETC) and many apparently lack the enzymes and transporters required for fatty acid b-oxidation [8,9]. Furthermore, the pyruvate dehydrogenase complex (PDH) responsible for conversion of pyruvate into acetyl-CoA -an obligate fuel for the TCA cycle -is only present in the apicoplast [10]. Consequently, there was no obvious entry point to allow catalysis of glycolytic pyruvate by the TCA cycle [10][11][12][13][14]. Despite this, there is overwhelming evidence that apicomplexans rely on a functional and canonical TCA cycle (as reviewed [4,5,15]), and apicomplexan genome annotations indicate the presence of all enzymes of the TCA cycle. Only one clade of apicomplexans, Cryptosporidium spp., show evidence of outright loss of the TCA cycle, but these taxa retain only a highly reduced mitochondrion, the mitosome, and have also lost their apicoplast [5,8,16].This review highlights how metabolomics technologies coupled to genetic manipulation have helped in unraveling apicomplexan parasite plasticity in carbon source utilization through different life stages, revealing a complex and sometimes counter-intuitive pattern of metabolic gains, losses, and reassignments. These changes have presumably been tailored to allow these parasites to thrive within their various host niches, but may constitute some much-needed Achilles' heels in the fight against these devastating diseases. Plasmodium falciparum and the Glycolytic DeceitGlycolysis has long appeared to be the main source of ATP and NAD(P)H in the erythrocytic stages of the malaria parasites, [5,[17][18][19][20][21]. Indeed, glucose uptake in P. falciparum-infected red blood cells (RBCs) has been observed to increase 75-100-fold compared to uninfected RBC [22][23][24][25]. Up to 93% of glucose is converted directly to lactate in asexual stages [26][ 4 _ T D $ D I F F ] and is ultimately excreted into the surrounding host cell. Perturbation of glucose uptake is detrimental to parasite growth [27,28], suggesting that glycolysis is an important part of the parasite's strategy for rapid proliferation. In a manner analogous to the Warburg effect observed in highly-proliferative cancer lines and other rapidly-growing cells (e.g., yeast and bloodstream Trypanosoma spp.), Plasmodium (in erythrocytic stages) has opted for fast generation of ATP through substrate-level phosphorylation and secretion of lactate as an end-product (aerobic fermentative glycolysis), as opposed to the 'slow but efficient' mitochondrial oxidative phosphorylation and complete oxidation [29]. Reasons for this dependence on glycolytic fermentation remain unclear -after all, blood stages of Plasmodium certainly have access to oxygen -but it may be a way of avoiding excessiv...

show abstract

The Plasmodium falciparum sexual development transcriptome: A microarray analysis using ontology-based pattern identification

Cited by 311 publications

References 68 publications

Statistical estimation of cell-cycle progression and lineage commitment in Plasmodium falciparum reveals a homogeneous pattern of transcription in ex vivo culture

Statistical estimation of cell-cycle progression and lineage commitment in Plasmodium falciparum reveals a homogeneous pattern of transcription in ex vivo culture

The development of malaria parasites in the mosquito midgut

Apicomplexan Energy Metabolism: Carbon Source Promiscuity and the Quiescence Hyperbole

Contact Info

Product

Resources

About