A combined transcriptome and proteome survey of malaria parasite liver stages

Tarun, Alice S.; Peng, Xinxia; Dumpit, Ronald F.; Ogata, Yuko; Silva-Rivera, Hilda; Camargo, Nelly; Daly, Thomas M.; Bergman, Lawrence W.; Kappe, Stefan H. I.

doi:10.1073/pnas.0710780104

Cited by 345 publications

(409 citation statements)

References 42 publications

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“…However, treatment of parasites later in development, from 24 hpi, would not block this initial production of transcripts, meaning that drugs targeting translation, but not blocking transcription would be successful in blocking production of apicoplast proteins and leading to prevention of parasite maturation. As we observed an effect of rifampicin on HepG2 cell proliferation, it is also possible that when rifampicin is applied early (Tarun et al, 2008) compared with late (present study) in exo-erythrocytic Plasmodium infection, parasites are more susceptible to effects on the HepG2 cell stemming from rifampicin treatment.…”

Section: Treatment Of Exo-erythrocytic Parasites With the Anti-microbmentioning

confidence: 55%

“…In contrast with this, using rifampicin at a concentration more than 6 times higher than any of the IC 50 values determined for P. falciparum, we failed to see an effect of the antibiotic on the growth of the apicoplast and failed to see a block in the development of the mature form of the exo-erythrocytic stage parasite. Recently, it has been observed that rifampicin leads to a block in the development of exo-erythrocytic parasites, as determined 40 hpi and when treatment of parasites was carried out from the starting point of infection (Tarun et al, 2008). This finding may reveal a higher sensitivity of the extracellular sporozoite to the antibiotic, preventing invasion or successful establishment of an exo-erythrocytic infection.…”

Section: Treatment Of Exo-erythrocytic Parasites With the Anti-microbmentioning

confidence: 94%

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GFP‐targeting allows visualization of the apicoplast throughout the life cycle of live malaria parasites

Stanway

Witt

Zobiak

et al. 2009

Biology of the Cell

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Background information. The Plasmodium parasite, during its life cycle, undergoes three phases of asexual reproduction, these being repeated rounds of erythrocytic schizogony, sporogony within oocysts on the mosquito midgut wall and exo-erythrocytic schizogony within the hepatocyte. During each phase of asexual reproduction, the parasite must ensure that every new daughter cell contains an apicoplast, as this organelle cannot be formed de novo and is essential for parasite survival. To date, studies visualizing the apicoplast in live Plasmodium parasites have been restricted to the blood stages of Plasmodium falciparum.Results. In the present study, we have generated Plasmodium berghei parasites in which GFP (green fluorescent protein) is targeted to the apicoplast using the specific targeting sequence of ACP (acyl carrier protein), which has allowed us to visualize this organelle in live Plasmodium parasites. During each phase of asexual reproduction, the apicoplast becomes highly branched, but remains as a single organelle until the completion of nuclear division, whereupon it divides and is rapidly segregated into newly forming daughter cells. We have shown that the antimicrobial agents azithromycin, clindamycin and doxycycline block development of the apicoplast during exo-erythrocytic schizogony in vitro, leading to impaired parasite maturation.Conclusions. Using a range of powerful live microscopy techniques, we show for the first time the development of a Plasmodium organelle through the entire life cycle of the parasite. Evidence is provided that interference with the development of the Plasmodium apicoplast results in the failure to produce red-blood-cell-infective merozoites.

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Section: Treatment Of Exo-erythrocytic Parasites With the Anti-microbmentioning

confidence: 55%

Section: Treatment Of Exo-erythrocytic Parasites With the Anti-microbmentioning

confidence: 94%

GFP‐targeting allows visualization of the apicoplast throughout the life cycle of live malaria parasites

Stanway

Witt

Zobiak

et al. 2009

Biology of the Cell

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“…29 Overall, our predicted data provide a strong rationale for developing asexual blood-stage vaccine component as part of a multivalent effective malaria vaccine that may need to incorporate antigens of several life-cycle stages including liver stage. [64][65][66][67] …”

Section: Resultsmentioning

confidence: 99%

Characterization of Plasmodium falciparum Proteome at Asexual Blood Stages for Screening of Effective Vaccine Candidates: An Immunoinformatics Approach

Singh

Verma

Mishra

2015

Immunol Immunogenet Insights

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Malaria is a complex parasitic disease that is currently causing great concerns globally owing to the resistance to antimalarial drugs and lack of an effective vaccine. The present study involves the characterization of extracellular secretory proteins as vaccine candidates derived from proteome analysis of Plasmodium falciparum at asexual blood stages of malaria. Among the screened 32 proteins, 31 were predicted as antigens by the VaxiJen program, and 26 proteins had less than two transmembrane spanning regions predicted using the THMMM program. Moreover, 10 and 5 proteins were predicted to contain secretory signals by SignalP and TargetP, respectively. T-cell epitope prediction using MULTIPRED2 and NetCTL programs revealed that most of the predicted antigens are immunogenic and contain more than 10% supertype and 5% promiscuous epitopes of HLA-A, -B, or -DR. We anticipate that T-cell immune responses against asexual blood stages of Plasmodium are dispersed on a relatively large number of parasite antigens. This is the first report, to the best of our knowledge, offering new insights, at the proteome level, for the putative screening of effective vaccine candidates against the malaria pathogen. The findings also suggest new ways forward for the modern omics-guided vaccine target discovery using reverse vaccinology.

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“…Triclosan inhibits fatty acid synthesis in bacteria by specifically targeting FabI (31)(32)(33). Recent proteomic (34), genomic (21), and real-time PCR analysis (22) of liver-stage parasites have shown the upregulation of enzymes of Type-II fatty acid synthesis. Blocking the activity of these upregulated enzymes may provide a solution for treating liver-stage infection.…”

Section: Discussionmentioning

confidence: 99%

Triclosan inhibit the growth of the late liver‐stage of Plasmodium

Singh

Surolia

2009

IUBMB Life

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SummaryAnnually, approximately two million human deaths are caused worldwide by malaria, most of them being children. Plasmodium falciparum is the leading cause of cerebral malaria, the most severe and fatal form of disease. Moreover, the emergence of resistant strains to the existing drugs has worsened the situation. Currently, primaquine is the only drug available for eliminating liver-stage parasites. Because of the emergence of resistant parasite strains, it becomes necessary to find new targets unique to the malaria parasites. In the Plasmodium species, the discovery of a distinct Type-II fatty-acid synthesis pathway has created an opportunity to target this pathway for the development of new inhibitors of malaria parasite growth. The present study explored the growth inhibition potential of triclosan in the case of liver-stage parasites. Liver-stage of Plasmodium is an excellent target for intervention due to very small parasite load as well as possibility of eliminating parasites before it can cause blood-stage infection. Here we report that triclosan inhibits the development of the Plasmodium liver-stage parasites.2009 IUBMB IUBMB Life, 61(9): 923-928, 2009

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A combined transcriptome and proteome survey of malaria parasite liver stages

Cited by 345 publications

References 42 publications

GFP‐targeting allows visualization of the apicoplast throughout the life cycle of live malaria parasites

GFP‐targeting allows visualization of the apicoplast throughout the life cycle of live malaria parasites

Characterization of Plasmodium falciparum Proteome at Asexual Blood Stages for Screening of Effective Vaccine Candidates: An Immunoinformatics Approach

Triclosan inhibit the growth of the late liver‐stage of Plasmodium

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