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  1. Article ; Online: Deciphering protein prenylation in endocytic trafficking in

    Carruthers, Vern B / Dou, Zhicheng

    mBio

    2024  Volume 15, Issue 4, Page(s) e0028324

    Abstract: Toxoplasma ... ...

    Abstract Toxoplasma gondii
    MeSH term(s) Animals ; Toxoplasma/metabolism ; Protein Prenylation ; Proteins/metabolism ; Organelles/metabolism ; Protein Transport
    Chemical Substances Proteins
    Language English
    Publishing date 2024-02-26
    Publishing country United States
    Document type Journal Article ; Comment
    ZDB-ID 2557172-2
    ISSN 2150-7511 ; 2161-2129
    ISSN (online) 2150-7511
    ISSN 2161-2129
    DOI 10.1128/mbio.00283-24
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Interrupting Toxoplasma's Regularly Scheduled Program of Egress.

    Carruthers, Vern B

    Trends in parasitology

    2019  Volume 35, Issue 5, Page(s) 338–340

    Abstract: Although many cellular components of the ... ...

    Abstract Although many cellular components of the Ca
    MeSH term(s) Guanylate Cyclase ; Phosphatidic Acids ; Signal Transduction ; Toxoplasma
    Chemical Substances Phosphatidic Acids ; Guanylate Cyclase (EC 4.6.1.2)
    Language English
    Publishing date 2019-04-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Comment
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2019.03.007
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Toxoplasma gondii excretion of glycolytic products is associated with acidification of the parasitophorous vacuole during parasite egress.

    Huynh, My-Hang / Carruthers, Vern B

    PLoS pathogens

    2022  Volume 18, Issue 5, Page(s) e1010139

    Abstract: The Toxoplasma gondii lytic cycle is a repetition of host cell invasion, replication, egress, and re-invasion into the next host cell. While the molecular players involved in egress have been studied in greater detail in recent years, the signals and ... ...

    Abstract The Toxoplasma gondii lytic cycle is a repetition of host cell invasion, replication, egress, and re-invasion into the next host cell. While the molecular players involved in egress have been studied in greater detail in recent years, the signals and pathways for triggering egress from the host cell have not been fully elucidated. A perforin-like protein, PLP1, has been shown to be necessary for permeabilizing the parasitophorous vacuole (PV) membrane or exit from the host cell. In vitro studies indicated that PLP1 is most active in acidic conditions, and indirect evidence using superecliptic pHluorin indicated that the PV pH drops prior to parasite egress. Using ratiometric pHluorin, a GFP variant that responds to changes in pH with changes in its bimodal excitation spectrum peaks, allowed us to directly measure the pH in the PV prior to and during egress by live-imaging microscopy. A statistically significant change was observed in PV pH during ionomycin or zaprinast induced egress in both wild-type RH and Δplp1 vacuoles compared to DMSO-treated vacuoles. Interestingly, if parasites are chemically paralyzed, a pH drop is still observed in RH but not in Δplp1 tachyzoites. This indicates that the pH drop is dependent on the presence of PLP1 or motility. Efforts to determine transporters, exchangers, or pumps that could contribute to the drop in PV pH identified two formate-nitrite transporters (FNTs). Auxin induced conditional knockdown and knockouts of FNT1 and FNT2 reduced the levels of lactate and pyruvate released by the parasites and lead to an abatement of vacuolar acidification. While additional transporters and molecules are undoubtedly involved, we provide evidence of a definitive reduction in vacuolar pH associated with induced and natural egress and characterize two transporters that contribute to the acidification.
    MeSH term(s) Animals ; Hydrogen-Ion Concentration ; Parasites/metabolism ; Perforin/metabolism ; Protozoan Proteins/metabolism ; Toxoplasma/metabolism ; Vacuoles/metabolism
    Chemical Substances Protozoan Proteins ; Perforin (126465-35-8)
    Language English
    Publishing date 2022-05-05
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1010139
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: The multifaceted interactions between pathogens and host ESCRT machinery.

    Rivera-Cuevas, Yolanda / Carruthers, Vern B

    PLoS pathogens

    2023  Volume 19, Issue 5, Page(s) e1011344

    Abstract: The Endosomal Sorting Complex Required for Transport (ESCRT) machinery consists of multiple protein complexes that coordinate vesicle budding away from the host cytosol. ESCRTs function in many fundamental cellular processes including the biogenesis of ... ...

    Abstract The Endosomal Sorting Complex Required for Transport (ESCRT) machinery consists of multiple protein complexes that coordinate vesicle budding away from the host cytosol. ESCRTs function in many fundamental cellular processes including the biogenesis of multivesicular bodies and exosomes, membrane repair and restoration, and cell abscission during cytokinesis. Work over the past 2 decades has shown that a diverse cohort of viruses critically rely upon host ESCRT machinery for virus replication and envelopment. More recent studies reported that intracellular bacteria and the intracellular parasite Toxoplasma gondii benefit from, antagonize, or exploit host ESCRT machinery to preserve their intracellular niche, gain resources, or egress from infected cells. Here, we review how intracellular pathogens interact with the ESCRT machinery of their hosts, highlighting the variety of strategies they use to bind ESCRT complexes using short linear amino acid motifs like those used by ESCRTs to sequentially assemble on target membranes. Future work exposing new mechanisms of this molecular mimicry will yield novel insight of how pathogens exploit host ESCRT machinery and how ESCRTs facilitate key cellular processes.
    MeSH term(s) Humans ; Protein Transport ; Virus Replication ; Exosomes/metabolism ; Cell Movement ; Endosomal Sorting Complexes Required for Transport/metabolism
    Chemical Substances Endosomal Sorting Complexes Required for Transport
    Language English
    Publishing date 2023-05-04
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 2205412-1
    ISSN 1553-7374 ; 1553-7374
    ISSN (online) 1553-7374
    ISSN 1553-7374
    DOI 10.1371/journal.ppat.1011344
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The multifaceted interactions between pathogens and host ESCRT machinery.

    Yolanda Rivera-Cuevas / Vern B Carruthers

    PLoS Pathogens, Vol 19, Iss 5, p e

    2023  Volume 1011344

    Abstract: The Endosomal Sorting Complex Required for Transport (ESCRT) machinery consists of multiple protein complexes that coordinate vesicle budding away from the host cytosol. ESCRTs function in many fundamental cellular processes including the biogenesis of ... ...

    Abstract The Endosomal Sorting Complex Required for Transport (ESCRT) machinery consists of multiple protein complexes that coordinate vesicle budding away from the host cytosol. ESCRTs function in many fundamental cellular processes including the biogenesis of multivesicular bodies and exosomes, membrane repair and restoration, and cell abscission during cytokinesis. Work over the past 2 decades has shown that a diverse cohort of viruses critically rely upon host ESCRT machinery for virus replication and envelopment. More recent studies reported that intracellular bacteria and the intracellular parasite Toxoplasma gondii benefit from, antagonize, or exploit host ESCRT machinery to preserve their intracellular niche, gain resources, or egress from infected cells. Here, we review how intracellular pathogens interact with the ESCRT machinery of their hosts, highlighting the variety of strategies they use to bind ESCRT complexes using short linear amino acid motifs like those used by ESCRTs to sequentially assemble on target membranes. Future work exposing new mechanisms of this molecular mimicry will yield novel insight of how pathogens exploit host ESCRT machinery and how ESCRTs facilitate key cellular processes.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: TgTKL4 Is a Novel Kinase That Plays an Important Role in

    Montano, Hilary / Anandkrishnan, Ramu / Carruthers, Vern B / Gaji, Rajshekhar Y

    mSphere

    2023  Volume 8, Issue 2, Page(s) e0064922

    Abstract: Protein kinases of the protozoan parasite Toxoplasma gondii have been shown to play key roles in regulating parasite motility, invasion, replication, egress and survival within the host. The tyrosine kinase-like (TKL) kinase family of proteins are a set ... ...

    Abstract Protein kinases of the protozoan parasite Toxoplasma gondii have been shown to play key roles in regulating parasite motility, invasion, replication, egress and survival within the host. The tyrosine kinase-like (TKL) kinase family of proteins are a set of poorly studied kinases that our recent studies have indicated play a critical role in
    MeSH term(s) Animals ; Mice ; Toxoplasma/metabolism ; Proteome/metabolism ; Protozoan Proteins/metabolism ; Toxoplasmosis/parasitology ; Cell Cycle ; Mammals
    Chemical Substances Proteome ; Protozoan Proteins
    Language English
    Publishing date 2023-02-14
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ISSN 2379-5042
    ISSN (online) 2379-5042
    DOI 10.1128/msphere.00649-22
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: A

    Piro, Federica / Masci, Silvia / Kannan, Geetha / Focaia, Riccardo / Schultz, Tracey L / Carruthers, Vern B / Di Cristina, Manlio

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Toxoplasma gondii: Importance: T. ... ...

    Abstract Toxoplasma gondii
    Importance: T. gondii
    Language English
    Publishing date 2023-09-01
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.31.555807
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Toxoplasma gondii excretion of glycolytic products is associated with acidification of the parasitophorous vacuole during parasite egress.

    My-Hang Huynh / Vern B Carruthers

    PLoS Pathogens, Vol 18, Iss 5, p e

    2022  Volume 1010139

    Abstract: The Toxoplasma gondii lytic cycle is a repetition of host cell invasion, replication, egress, and re-invasion into the next host cell. While the molecular players involved in egress have been studied in greater detail in recent years, the signals and ... ...

    Abstract The Toxoplasma gondii lytic cycle is a repetition of host cell invasion, replication, egress, and re-invasion into the next host cell. While the molecular players involved in egress have been studied in greater detail in recent years, the signals and pathways for triggering egress from the host cell have not been fully elucidated. A perforin-like protein, PLP1, has been shown to be necessary for permeabilizing the parasitophorous vacuole (PV) membrane or exit from the host cell. In vitro studies indicated that PLP1 is most active in acidic conditions, and indirect evidence using superecliptic pHluorin indicated that the PV pH drops prior to parasite egress. Using ratiometric pHluorin, a GFP variant that responds to changes in pH with changes in its bimodal excitation spectrum peaks, allowed us to directly measure the pH in the PV prior to and during egress by live-imaging microscopy. A statistically significant change was observed in PV pH during ionomycin or zaprinast induced egress in both wild-type RH and Δplp1 vacuoles compared to DMSO-treated vacuoles. Interestingly, if parasites are chemically paralyzed, a pH drop is still observed in RH but not in Δplp1 tachyzoites. This indicates that the pH drop is dependent on the presence of PLP1 or motility. Efforts to determine transporters, exchangers, or pumps that could contribute to the drop in PV pH identified two formate-nitrite transporters (FNTs). Auxin induced conditional knockdown and knockouts of FNT1 and FNT2 reduced the levels of lactate and pyruvate released by the parasites and lead to an abatement of vacuolar acidification. While additional transporters and molecules are undoubtedly involved, we provide evidence of a definitive reduction in vacuolar pH associated with induced and natural egress and characterize two transporters that contribute to the acidification.
    Keywords Immunologic diseases. Allergy ; RC581-607 ; Biology (General) ; QH301-705.5
    Subject code 572
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  9. Article ; Online: Toxoplasma gondii

    Schultz, Aric J / Carruthers, Vern B

    mSphere

    2018  Volume 3, Issue 1

    Abstract: Egress is a crucial phase of ... ...

    Abstract Egress is a crucial phase of the
    Language English
    Publishing date 2018-02-28
    Publishing country United States
    Document type Journal Article
    ISSN 2379-5042
    ISSN (online) 2379-5042
    DOI 10.1128/mSphereDirect.00073-18
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article: Interrupting Toxoplasma’s Regularly Scheduled Program of Egress

    Carruthers, Vern B

    Trends in parasitology. 2019 May, v. 35, no. 5

    2019  

    Abstract: Although many cellular components of the Ca2+ signaling pathway dictating Toxoplasma gondii egress have been identified, whether the parasite secretes protein activators of this pathway remained unknown. Bisio et al. (Nat. Microbiol. 2019;4:420–428) ... ...

    Abstract Although many cellular components of the Ca2+ signaling pathway dictating Toxoplasma gondii egress have been identified, whether the parasite secretes protein activators of this pathway remained unknown. Bisio et al. (Nat. Microbiol. 2019;4:420–428) identify a parasite-secreted diacylglycerol kinase as a key upstream activator of signaling for ‘programmed' egress from host cells.
    Keywords calcium ; calcium signaling ; diacylglycerol kinase ; parasites ; Toxoplasma gondii
    Language English
    Dates of publication 2019-05
    Size p. 338-340.
    Publishing place Elsevier Ltd
    Document type Article
    ZDB-ID 2036227-4
    ISSN 1471-5007 ; 1471-4922
    ISSN (online) 1471-5007
    ISSN 1471-4922
    DOI 10.1016/j.pt.2019.03.007
    Database NAL-Catalogue (AGRICOLA)

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