Plasmodium Parasites Viewed through Proteomics

Swearingen, Kristian E.; Lindner, Scott E.

doi:10.1016/j.pt.2018.08.003

Cited by 21 publications

(23 citation statements)

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“…Systems analysis of translational repression in sporozoites requires knowledge of their global transcriptomes and proteomes, but such analyses were greatly restricted due to substantial contamination with material from the mosquito vector and its microbiome in sporozoite samples 23–25 (reviewed in ref. 26,27 ). To address this, we have developed a scalable, discontinuous density gradient purification approach for sporozoites that greatly reduces contamination from the mosquito and its microbes 28 .…”

Section: Introductionmentioning

confidence: 99%

Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites

et al. 2019

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Plasmodium sporozoites are transmitted from infected mosquitoes to mammals, and must navigate the host skin and vasculature to infect the liver. This journey requires distinct proteomes. Here, we report the dynamic transcriptomes and proteomes of both oocyst sporozoites and salivary gland sporozoites in both rodent-infectious Plasmodium yoelii parasites and human-infectious Plasmodium falciparum parasites. The data robustly define mRNAs and proteins that are upregulated in oocyst sporozoites (UOS) or upregulated in infectious sporozoites (UIS) within the salivary glands, including many that are essential for sporozoite functions in the vector and host. Moreover, we find that malaria parasites use two overlapping, extensive, and independent programs of translational repression across sporozoite maturation to temporally regulate protein expression. Together with gene-specific validation experiments, these data indicate that two waves of translational repression are implemented and relieved at different times during sporozoite maturation, migration and infection, thus promoting their successful development and vector-to-host transition.

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Section: Introductionmentioning

confidence: 99%

Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites

et al. 2019

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“…Mass-spectrometry (MS) qualifies as an excellent tool for the identification and quantification of differentially regulated proteins that provide information about altered pathways and deeper insights into disease biology. Global and stage-specific mass spectrometric analyses of P. falciparum in culture have revealed important features of the parasite's biology [10] including sexual stages [11]. In 2012, Ray and coworkers applied a quantitative proteomics approach to identify differentially expressed host serum proteins in vivax and falciparum malaria patients.…”

Section: Introductionmentioning

confidence: 99%

Comprehensive proteomics investigation of P. vivax-infected human plasma and parasite isolates

et al. 2020

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Background: In recent times, Plasmodium vivax (P. vivax) has become a serious threat to public health due to its ability to cause severe infection with fatal outcomes. Its unique biology makes it resilient to control measures that are otherwise effective against P. falciparum. A deeper understanding of P. vivax biology and pathogenesis is, therefore, essential for developing the right control strategies. Proteomics of P. falciparum has been helpful in studying disease biology and elucidating molecular mechanisms involved in the development of disease. However, unlike P. falciparum, proteomics data for P. vivax infection is minimal due to the absence of a continuous culture system. The dependence on clinical samples and animal models has drastically limited P. vivax research, creating critical knowledge gaps in our understanding of the disease. This study describes an in-depth proteomics analysis of P. vivax-infected human plasma and parasite isolates, to understand parasite biology, pathogenesis, and to identify new diagnostic targets for P. vivax malaria. Methods: A mass-spectrometry-(MS) based proteomics approach (Q Exactive) was applied to analyze human plasma and parasite isolates from vivax malaria patients visiting a primary health centre in India. Additionally, a targeted proteomics assay was standardized for validating unique peptides of most recurring parasite proteins. Results: Thirty-eight P. vivax proteins were detected in human plasma with high confidence. Several glycolytic enzymes were found along with hypothetical, cytoskeletal, ribosomal, and nuclear proteins. Additionally, 103 highly abundant P. vivax proteins were detected in parasite isolates. This represents the highest number of parasite proteins to be reported from clinical samples so far. Interestingly, five of these; three Plasmodium exported proteins (PVX_003545, PVX_003555 and PVX_121935), a hypothetical protein (PVX_083555) and Pvstp1 (subtelomeric transmembrane protein 1, PVX_094303) were found in both plasma and parasite isolates. Conclusions: A parasite proteomics investigation is essential to understand disease pathobiology and design novel interventions. Control strategies against P. vivax also depend on early diagnosis. This work provides deeper insights into the biology of P. vivax by identifying proteins expressed by the parasite during its complex life-cycle within the human host. The study also reports antigens that may be explored as diagnostic candidates.

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“…Proteomic analyses of the parasite's plasma membrane and/or organelles are also beginning to contribute valuable insights into the likely subcellular locations of Plasmodium transporters (reviewed by (Swearingen & Lindner, ). These studies have included characterisations of the protein contents of the digestive vacuole (Lamarque et al ., ), the parasitophorous vacuole (Schnider et al ., ), the apicoplast (Boucher et al ., ), and the sporozoite surface (Swearingen et al ., ).…”

Section: The Plasmodium Transportomementioning

confidence: 99%

The transportome of the malaria parasite

Martin

2019

Biological Reviews

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Membrane transport proteins, also known as transporters, control the movement of ions, nutrients, metabolites, and waste products across the membranes of a cell and are central to its biology. Proteins of this type also serve as drug targets and are key players in the phenomenon of drug resistance. The malaria parasite has a relatively reduced transportome, with only approximately 2.5% of its genes encoding transporters. Even so, assigning functions and physiological roles to these proteins, and ascertaining their contributions to drug action and drug resistance, has been very challenging. This review presents a detailed critique and synthesis of the disruption phenotypes, protein subcellular localisations, protein functions (observed or predicted), and links to antimalarial drug resistance for each of the parasite's transporter genes. The breadth and depth of the gene disruption data are particularly impressive, with at least one phenotype determined in the parasite's asexual blood stage for each transporter gene, and multiple phenotypes available for 76% of the genes. Analysis of the curated data set revealed there to be relatively little redundancy in the Plasmodium transportome; almost two‐thirds of the parasite's transporter genes are essential or required for normal growth in the asexual blood stage of the parasite, and this proportion increased to 78% when the disruption phenotypes available for the other parasite life stages were included in the analysis. These observations, together with the finding that 22% of the transportome is implicated in the parasite's resistance to existing antimalarials and/or drugs within the development pipeline, indicate that transporters are likely to serve, or are already serving, as drug targets. Integration of the different biological and bioinformatic data sets also enabled the selection of candidates for transport processes known to be essential for parasite survival, but for which the underlying proteins have thus far remained undiscovered. These include potential transporters of pantothenate, isoleucine, or isopentenyl diphosphate, as well as putative anion‐selective channels that may serve as the pore component of the parasite's ‘new permeation pathways’. Other novel insights into the parasite's biology included the identification of transporters for the potential development of antimalarial treatments, transmission‐blocking drugs, prophylactics, and genetically attenuated vaccines. The syntheses presented herein set a foundation for elucidating the functions and physiological roles of key members of the Plasmodium transportome and, ultimately, to explore and realise their potential as therapeutic targets.

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Plasmodium Parasites Viewed through Proteomics

Cited by 21 publications

References 99 publications

Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites

Transcriptomics and proteomics reveal two waves of translational repression during the maturation of malaria parasite sporozoites

Comprehensive proteomics investigation of P. vivax-infected human plasma and parasite isolates

The transportome of the malaria parasite

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