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  1. Article ; Online: A novel computational pipeline for

    Andradi-Brown, Clare / Wichers-Misterek, Jan Stephan / von Thien, Heidrun / Höppner, Yannick D / Scholz, Judith A M / Hansson, Helle / Filtenborg Hocke, Emma / Gilberger, Tim Wolf / Duffy, Michael F / Lavstsen, Thomas / Baum, Jake / Otto, Thomas D / Cunnington, Aubrey J / Bachmann, Anna

    eLife

    2024  Volume 12

    Abstract: The pathogenesis of ... ...

    Abstract The pathogenesis of severe
    MeSH term(s) Humans ; Plasmodium falciparum/genetics ; Transcriptome ; Malaria, Falciparum ; Benchmarking ; Emotions
    Language English
    Publishing date 2024-01-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2687154-3
    ISSN 2050-084X ; 2050-084X
    ISSN (online) 2050-084X
    ISSN 2050-084X
    DOI 10.7554/eLife.87726
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: A Microtubule-Associated Protein Is Essential for Malaria Parasite Transmission.

    Wichers-Misterek, Jan Stephan / Binder, Annika M / Mesén-Ramírez, Paolo / Dorner, Lilian Patrick / Safavi, Soraya / Fuchs, Gwendolin / Lenz, Tobias L / Bachmann, Anna / Wilson, Danny / Frischknecht, Friedrich / Gilberger, Tim-Wolf

    mBio

    2023  Volume 14, Issue 1, Page(s) e0331822

    Abstract: Mature gametocytes of Plasmodium falciparum display a banana (falciform) shape conferred by a complex array of subpellicular microtubules (SPMT) associated with the inner membrane complex (IMC). Microtubule-associated proteins (MAPs) define MT ... ...

    Abstract Mature gametocytes of Plasmodium falciparum display a banana (falciform) shape conferred by a complex array of subpellicular microtubules (SPMT) associated with the inner membrane complex (IMC). Microtubule-associated proteins (MAPs) define MT populations and modulate interaction with pellicular components. Several MAPs have been identified in Toxoplasma gondii, and homologues can be found in the genomes of
    MeSH term(s) Animals ; Humans ; Parasites/metabolism ; Microtubule-Associated Proteins ; Plasmodium falciparum/metabolism ; Malaria ; Plasmodium berghei ; Sporozoites ; Protozoan Proteins/metabolism
    Chemical Substances Microtubule-Associated Proteins ; Protozoan Proteins
    Language English
    Publishing date 2023-01-10
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.03318-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Erratum for Wichers-Misterek et al., "A Microtubule-Associated Protein Is Essential for Malaria Parasite Transmission".

    Wichers-Misterek, Jan Stephan / Binder, Annika M / Mesén-Ramírez, Paolo / Dorner, Lilian Patrick / Safavi, Soraya / Fuchs, Gwendolin / Lenz, Tobias L / Bachmann, Anna / Wilson, Danny / Frischknecht, Friedrich / Gilberger, Tim-Wolf

    mBio

    2023  Volume 14, Issue 5, Page(s) e0178623

    Language English
    Publishing date 2023-09-29
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.01786-23
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The Kelch13 compartment contains highly divergent vesicle trafficking proteins in malaria parasites.

    Schmidt, Sabine / Wichers-Misterek, Jan Stephan / Behrens, Hannah Michaela / Birnbaum, Jakob / Henshall, Isabelle G / Dröge, Jana / Jonscher, Ernst / Flemming, Sven / Castro-Peña, Carolina / Mesén-Ramírez, Paolo / Spielmann, Tobias

    PLoS pathogens

    2023  Volume 19, Issue 12, Page(s) e1011814

    Abstract: Single amino acid changes in the parasite protein Kelch13 (K13) result in reduced susceptibility of P. falciparum parasites to artemisinin and its derivatives (ART). Recent work indicated that K13 and other proteins co-localising with K13 (K13 ... ...

    Abstract Single amino acid changes in the parasite protein Kelch13 (K13) result in reduced susceptibility of P. falciparum parasites to artemisinin and its derivatives (ART). Recent work indicated that K13 and other proteins co-localising with K13 (K13 compartment proteins) are involved in the endocytic uptake of host cell cytosol (HCCU) and that a reduction in HCCU results in reduced susceptibility to ART. HCCU is critical for parasite survival but is poorly understood, with the K13 compartment proteins among the few proteins so far functionally linked to this process. Here we further defined the composition of the K13 compartment by analysing more hits from a previous BioID, showing that MyoF and MCA2 as well as Kelch13 interaction candidate (KIC) 11 and 12 are found at this site. Functional analyses, tests for ART susceptibility as well as comparisons of structural similarities using AlphaFold2 predictions of these and previously identified proteins showed that vesicle trafficking and endocytosis domains were frequent in proteins involved in resistance or endocytosis (or both), comprising one group of K13 compartment proteins. While this strengthened the link of the K13 compartment to endocytosis, many proteins of this group showed unusual domain combinations and large parasite-specific regions, indicating a high level of taxon-specific adaptation of this process. Another group of K13 compartment proteins did not influence endocytosis or ART susceptibility and lacked detectable vesicle trafficking domains. We here identified the first protein of this group that is important for asexual blood stage development and showed that it likely is involved in invasion. Overall, this work identified novel proteins functioning in endocytosis and at the K13 compartment. Together with comparisons of structural predictions it provides a repertoire of functional domains at the K13 compartment that indicate a high level of adaption of endocytosis in malaria parasites.
    MeSH term(s) Animals ; Antimalarials/pharmacology ; Plasmodium falciparum/metabolism ; Parasites/metabolism ; Protozoan Proteins/genetics ; Protozoan Proteins/metabolism ; Drug Resistance ; Malaria, Falciparum/parasitology ; Mutation
    Chemical Substances Antimalarials ; Protozoan Proteins
    Language English
    Publishing date 2023-12-01
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011814
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Gene-by-gene screen of the unknown proteins encoded on Plasmodium falciparum chromosome 3.

    Kimmel, Jessica / Schmitt, Marius / Sinner, Alexej / Jansen, Pascal Wilhelmus Theodorus Christianus / Mainye, Sheila / Ramón-Zamorano, Gala / Toenhake, Christa Geeke / Wichers-Misterek, Jan Stephan / Cronshagen, Jakob / Sabitzki, Ricarda / Mesén-Ramírez, Paolo / Behrens, Hannah Michaela / Bártfai, Richárd / Spielmann, Tobias

    Cell systems

    2023  Volume 14, Issue 1, Page(s) 9–23.e7

    Abstract: Taxon-specific proteins are key determinants defining the biology of all organisms and represent prime drug targets in pathogens. However, lacking comparability with proteins in other lineages makes them particularly difficult to study. In malaria ... ...

    Abstract Taxon-specific proteins are key determinants defining the biology of all organisms and represent prime drug targets in pathogens. However, lacking comparability with proteins in other lineages makes them particularly difficult to study. In malaria parasites, this is exacerbated by technical limitations. Here, we analyzed the cellular location, essentiality, function, and, in selected cases, interactome of all unknown non-secretory proteins encoded on an entire P. falciparum chromosome. The nucleus was the most common localization, indicating that it is a hotspot of parasite-specific biology. More in-depth functional studies with four proteins revealed essential roles in DNA replication and mitosis. The mitosis proteins defined a possible orphan complex and a highly diverged complex needed for spindle-kinetochore connection. Structure-function comparisons indicated that the taxon-specific proteins evolved by different mechanisms. This work demonstrates the feasibility of gene-by-gene screens to elucidate the biology of malaria parasites and reveal critical parasite-specific processes of interest as drug targets.
    MeSH term(s) Humans ; Plasmodium falciparum/genetics ; Chromosomes, Human, Pair 3 ; Kinetochores ; Mitosis ; Malaria
    Language English
    Publishing date 2023-01-19
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2854138-8
    ISSN 2405-4720 ; 2405-4712
    ISSN (online) 2405-4720
    ISSN 2405-4712
    DOI 10.1016/j.cels.2022.12.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: The exception that proves the rule: Virulence gene expression at the onset of Plasmodium falciparum blood stage infections.

    Wichers-Misterek, Jan Stephan / Krumkamp, Ralf / Held, Jana / von Thien, Heidrun / Wittmann, Irene / Höppner, Yannick Daniel / Ruge, Julia M / Moser, Kara / Dara, Antoine / Strauss, Jan / Esen, Meral / Fendel, Rolf / Sulyok, Zita / Jeninga, Myriam D / Kremsner, Peter G / Sim, B Kim Lee / Hoffman, Stephen L / Duffy, Michael F / Otto, Thomas D /
    Gilberger, Tim-Wolf / Silva, Joana C / Mordmüller, Benjamin / Petter, Michaela / Bachmann, Anna

    PLoS pathogens

    2023  Volume 19, Issue 6, Page(s) e1011468

    Abstract: Controlled human malaria infections (CHMI) are a valuable tool to study parasite gene expression in vivo under defined conditions. In previous studies, virulence gene expression was analyzed in samples from volunteers infected with the Plasmodium ... ...

    Abstract Controlled human malaria infections (CHMI) are a valuable tool to study parasite gene expression in vivo under defined conditions. In previous studies, virulence gene expression was analyzed in samples from volunteers infected with the Plasmodium falciparum (Pf) NF54 isolate, which is of African origin. Here, we provide an in-depth investigation of parasite virulence gene expression in malaria-naïve European volunteers undergoing CHMI with the genetically distinct Pf 7G8 clone, originating in Brazil. Differential expression of var genes, encoding major virulence factors of Pf, PfEMP1s, was assessed in ex vivo parasite samples as well as in parasites from the in vitro cell bank culture that was used to generate the sporozoites (SPZ) for CHMI (Sanaria PfSPZ Challenge (7G8)). We report broad activation of mainly B-type subtelomeric located var genes at the onset of a 7G8 blood stage infection in naïve volunteers, mirroring the NF54 expression study and suggesting that the expression of virulence-associated genes is generally reset during transmission from the mosquito to the human host. However, in 7G8 parasites, we additionally detected a continuously expressed single C-type variant, Pf7G8_040025600, that was most highly expressed in both pre-mosquito cell bank and volunteer samples, suggesting that 7G8, unlike NF54, maintains expression of some previously expressed var variants during transmission. This suggests that in a new host, the parasite may preferentially express the variants that previously allowed successful infection and transmission. Trial registration: ClinicalTrials.gov - NCT02704533; 2018-004523-36.
    MeSH term(s) Animals ; Humans ; Culicidae/genetics ; Gene Expression ; Malaria ; Malaria, Falciparum/genetics ; Malaria, Falciparum/parasitology ; Parasites/genetics ; Plasmodium falciparum/genetics ; Sporozoites ; Virulence/genetics
    Language English
    Publishing date 2023-06-29
    Publishing country United States
    Document type Clinical Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011468
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: The exception that proves the rule

    Wichers-Misterek, Jan Stephan / Krumkamp, Ralf / Held, Jana / Thien, Heidrun von / Wittmann, Irene / Höppner, Yannick Daniel / Ruge, Julia M. / Moser, Kara / Dara, Antoine / Strauss, Jan / Esen, Meral / Fendel, Rolf / Sulyok, Zita / Kremsner, Peter G. / Sim, B. Kim Lee / Hoffman, Stephen L. / Duffy, Michael F. / Otto, Thomas D. / Gilberger, Tim-Wolf /
    Silva, Joana C. / Mordmüller, Benjamin / Petter, Michaela / Bachmann, Anna

    Virulence gene expression at the onset of Plasmodium falciparum blood stage infections

    2022  

    Language English
    Publishing country de
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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