A Toxoplasma gondii putative amino acid transporter localizes to the plant-like vacuolar compartment and controls parasite extracellular survival and stage differentiation
is a protozoan parasite that infects a broad spectrum of hosts and can colonize many organs and cell types. The ability to reside within a wide range of different niches requires substantial adaptability to diverse microenvironments. Very little is known about how this parasite senses various milieu...
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description | is a protozoan parasite that infects a broad spectrum of hosts and can colonize many organs and cell types. The ability to reside within a wide range of different niches requires substantial adaptability to diverse microenvironments. Very little is known about how this parasite senses various milieus and adapts its metabolism to survive, replicate during the acute stage, and then differentiate to the chronic stage.
possesses a lysosome-like organelle known as the plant-like vacuolar compartment (PLVAC), which serves various functions, including digestion, ion storage and homeostasis, endocytosis, and autophagy. Lysosomes are critical for maintaining cellular health and function by degrading waste materials and recycling components. To supply the cell with the essential building blocks and energy sources required for the maintenance of its functions and structures, the digested solutes generated within the lysosome are transported into the cytosol by proteins embedded in the lysosomal membrane. Currently, a limited number of PLVAC transporters have been characterized, with TgCRT being the sole potential transporter of amino acids and small peptides identified thus far. To bridge this knowledge gap, we used lysosomal amino acid transporters from other organisms as queries to search the
proteome. This led to the identification of four potential amino acid transporters, which we have designated as TgAAT1-4. Assessing their expression and sub-cellular localization, we found that one of them, TgAAT1, localized to the PLVAC and is necessary for normal parasite extracellular survival and bradyzoite differentiation. Moreover, we present preliminary data showing the possible involvement of TgAAT1 in the PLVAC transport of arginine.IMPORTANCE
is a highly successful parasite infecting a broad range of warm-blooded organisms, including about one-third of all humans. Although
infections rarely result in symptomatic disease in individuals with a healthy immune system, the incredibly high number of persons infected, along with the risk of severe infection in immunocompromised patients and the potential link of chronic infection to mental disorders, makes this infection a significant public health concern. As a result, there is a pressing need for new treatment approaches that are both effective and well tolerated. The limitations in understanding how
manages its metabolism to adapt to changing environments and triggers its transformation into bradyzoites have hindered the |
doi_str_mv | 10.1128/msphere.00597-23 |
format | Article |
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possesses a lysosome-like organelle known as the plant-like vacuolar compartment (PLVAC), which serves various functions, including digestion, ion storage and homeostasis, endocytosis, and autophagy. Lysosomes are critical for maintaining cellular health and function by degrading waste materials and recycling components. To supply the cell with the essential building blocks and energy sources required for the maintenance of its functions and structures, the digested solutes generated within the lysosome are transported into the cytosol by proteins embedded in the lysosomal membrane. Currently, a limited number of PLVAC transporters have been characterized, with TgCRT being the sole potential transporter of amino acids and small peptides identified thus far. To bridge this knowledge gap, we used lysosomal amino acid transporters from other organisms as queries to search the
proteome. This led to the identification of four potential amino acid transporters, which we have designated as TgAAT1-4. Assessing their expression and sub-cellular localization, we found that one of them, TgAAT1, localized to the PLVAC and is necessary for normal parasite extracellular survival and bradyzoite differentiation. Moreover, we present preliminary data showing the possible involvement of TgAAT1 in the PLVAC transport of arginine.IMPORTANCE
is a highly successful parasite infecting a broad range of warm-blooded organisms, including about one-third of all humans. Although
infections rarely result in symptomatic disease in individuals with a healthy immune system, the incredibly high number of persons infected, along with the risk of severe infection in immunocompromised patients and the potential link of chronic infection to mental disorders, makes this infection a significant public health concern. As a result, there is a pressing need for new treatment approaches that are both effective and well tolerated. The limitations in understanding how
manages its metabolism to adapt to changing environments and triggers its transformation into bradyzoites have hindered the discovery of vulnerabilities in its metabolic pathways or nutrient acquisition mechanisms to identify new therapeutic targets. In this work, we have shown that the lysosome-like organelle plant-like vacuolar compartment (PLVAC), acting through the putative arginine transporter TgAAT1, plays a pivotal role in regulating the parasite's extracellular survival and differentiation into bradyzoites.</description><identifier>ISSN: 2379-5042</identifier><identifier>EISSN: 2379-5042</identifier><identifier>DOI: 10.1128/msphere.00597-23</identifier><identifier>PMID: 38051073</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Adaptability ; Amino Acid Transport Systems - metabolism ; Amino acids ; Animals ; Arginine - metabolism ; Autophagy ; Bradyzoites ; Chronic infection ; Cytosol ; Endocytosis ; Homeostasis ; Humans ; Hypotheses ; Immune system ; Immunocompromised hosts ; Localization ; Lysosomes ; Mental disorders ; Metabolic pathways ; Metabolism ; Microenvironments ; Parasites ; Parasitology ; Peptides ; Protein turnover ; Proteins ; Proteomes ; Protozoa ; Public health ; Research Article ; Solutes ; Therapeutic targets ; Toxicity ; Toxoplasma - metabolism ; Toxoplasma gondii ; Vacuoles - metabolism</subject><ispartof>mSphere, 2024-01, Vol.9 (1), p.e0059723-e0059723</ispartof><rights>Copyright © 2023 Piro et al.</rights><rights>Copyright © 2023 Piro et al. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a360t-c53106b34195d457fd1075ce16142fe123360b1329ecae3662452406c7aa31bf3</cites><orcidid>0000-0003-4154-5210 ; 0000-0001-6859-8895</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://journals.asm.org/doi/pdf/10.1128/msphere.00597-23$$EPDF$$P50$$Gasm2$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://journals.asm.org/doi/full/10.1128/msphere.00597-23$$EHTML$$P50$$Gasm2$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,864,3188,27924,27925,52751,52752,52753</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38051073$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Blader, Ira J.</contributor><creatorcontrib>Piro, Federica</creatorcontrib><creatorcontrib>Masci, Silvia</creatorcontrib><creatorcontrib>Kannan, Geetha</creatorcontrib><creatorcontrib>Focaia, Riccardo</creatorcontrib><creatorcontrib>Schultz, Tracey L</creatorcontrib><creatorcontrib>Thaprawat, Pariyamon</creatorcontrib><creatorcontrib>Carruthers, Vern B</creatorcontrib><creatorcontrib>Di Cristina, Manlio</creatorcontrib><title>A Toxoplasma gondii putative amino acid transporter localizes to the plant-like vacuolar compartment and controls parasite extracellular survival and stage differentiation</title><title>mSphere</title><addtitle>mSphere</addtitle><addtitle>mSphere</addtitle><description>is a protozoan parasite that infects a broad spectrum of hosts and can colonize many organs and cell types. The ability to reside within a wide range of different niches requires substantial adaptability to diverse microenvironments. Very little is known about how this parasite senses various milieus and adapts its metabolism to survive, replicate during the acute stage, and then differentiate to the chronic stage.
possesses a lysosome-like organelle known as the plant-like vacuolar compartment (PLVAC), which serves various functions, including digestion, ion storage and homeostasis, endocytosis, and autophagy. Lysosomes are critical for maintaining cellular health and function by degrading waste materials and recycling components. To supply the cell with the essential building blocks and energy sources required for the maintenance of its functions and structures, the digested solutes generated within the lysosome are transported into the cytosol by proteins embedded in the lysosomal membrane. Currently, a limited number of PLVAC transporters have been characterized, with TgCRT being the sole potential transporter of amino acids and small peptides identified thus far. To bridge this knowledge gap, we used lysosomal amino acid transporters from other organisms as queries to search the
proteome. This led to the identification of four potential amino acid transporters, which we have designated as TgAAT1-4. Assessing their expression and sub-cellular localization, we found that one of them, TgAAT1, localized to the PLVAC and is necessary for normal parasite extracellular survival and bradyzoite differentiation. Moreover, we present preliminary data showing the possible involvement of TgAAT1 in the PLVAC transport of arginine.IMPORTANCE
is a highly successful parasite infecting a broad range of warm-blooded organisms, including about one-third of all humans. Although
infections rarely result in symptomatic disease in individuals with a healthy immune system, the incredibly high number of persons infected, along with the risk of severe infection in immunocompromised patients and the potential link of chronic infection to mental disorders, makes this infection a significant public health concern. As a result, there is a pressing need for new treatment approaches that are both effective and well tolerated. The limitations in understanding how
manages its metabolism to adapt to changing environments and triggers its transformation into bradyzoites have hindered the discovery of vulnerabilities in its metabolic pathways or nutrient acquisition mechanisms to identify new therapeutic targets. In this work, we have shown that the lysosome-like organelle plant-like vacuolar compartment (PLVAC), acting through the putative arginine transporter TgAAT1, plays a pivotal role in regulating the parasite's extracellular survival and differentiation into bradyzoites.</description><subject>Adaptability</subject><subject>Amino Acid Transport Systems - metabolism</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Arginine - metabolism</subject><subject>Autophagy</subject><subject>Bradyzoites</subject><subject>Chronic infection</subject><subject>Cytosol</subject><subject>Endocytosis</subject><subject>Homeostasis</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Immune system</subject><subject>Immunocompromised hosts</subject><subject>Localization</subject><subject>Lysosomes</subject><subject>Mental disorders</subject><subject>Metabolic pathways</subject><subject>Metabolism</subject><subject>Microenvironments</subject><subject>Parasites</subject><subject>Parasitology</subject><subject>Peptides</subject><subject>Protein turnover</subject><subject>Proteins</subject><subject>Proteomes</subject><subject>Protozoa</subject><subject>Public health</subject><subject>Research Article</subject><subject>Solutes</subject><subject>Therapeutic targets</subject><subject>Toxicity</subject><subject>Toxoplasma - metabolism</subject><subject>Toxoplasma gondii</subject><subject>Vacuoles - metabolism</subject><issn>2379-5042</issn><issn>2379-5042</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9kTtPHDEUhS2UCNCGPlVkKU2aIX6MPTslQnlJSGlIbd313AETjz2xPSvIX8qfjJfdPERB5Ye-c-65OoS85uycc7F-P-X5FhOeM6b6rhHyiJwK2fWNYq148d_9hJzlfMcY41po3eljciLXTHHWyVPy64Jex_s4e8gT0JsYBufovBQobosUJhciBesGWhKEPMdUMFEfLXj3EzMtkZZbpFUeSuPdd6RbsEv0kKiN0wypTBgKhTDUdygp-kzrL2RXkOJ9NbXo_bLj85K2bgv-Ec4FbpAObhzrhqG4GieGV-TlCD7j2eFckW8fP1xffm6uvn76cnlx1YDUrDRWSc70Rra8V0OrunGoqyqLXPNWjMiFrNiGS9GjBZRai1aJlmnbAUi-GeWKvNv7zin-WDAXM7m8ywkB45KNWPfrXu00FX37BL2LSwo1nRG9lIqrrueVYnvKpphzwtHMyU2QHgxnZtelOXRpHrs0NeGKNHtJ7UX8M32Gf3MIsmwmHP4O-NO0_A1USK4l</recordid><startdate>20240130</startdate><enddate>20240130</enddate><creator>Piro, Federica</creator><creator>Masci, Silvia</creator><creator>Kannan, Geetha</creator><creator>Focaia, Riccardo</creator><creator>Schultz, Tracey L</creator><creator>Thaprawat, Pariyamon</creator><creator>Carruthers, Vern B</creator><creator>Di Cristina, Manlio</creator><general>American Society for Microbiology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-4154-5210</orcidid><orcidid>https://orcid.org/0000-0001-6859-8895</orcidid></search><sort><creationdate>20240130</creationdate><title>A Toxoplasma gondii putative amino acid transporter localizes to the plant-like vacuolar compartment and controls parasite extracellular survival and stage differentiation</title><author>Piro, Federica ; Masci, Silvia ; Kannan, Geetha ; Focaia, Riccardo ; Schultz, Tracey L ; Thaprawat, Pariyamon ; Carruthers, Vern B ; Di Cristina, Manlio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a360t-c53106b34195d457fd1075ce16142fe123360b1329ecae3662452406c7aa31bf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adaptability</topic><topic>Amino Acid Transport Systems - metabolism</topic><topic>Amino acids</topic><topic>Animals</topic><topic>Arginine - metabolism</topic><topic>Autophagy</topic><topic>Bradyzoites</topic><topic>Chronic infection</topic><topic>Cytosol</topic><topic>Endocytosis</topic><topic>Homeostasis</topic><topic>Humans</topic><topic>Hypotheses</topic><topic>Immune system</topic><topic>Immunocompromised hosts</topic><topic>Localization</topic><topic>Lysosomes</topic><topic>Mental disorders</topic><topic>Metabolic pathways</topic><topic>Metabolism</topic><topic>Microenvironments</topic><topic>Parasites</topic><topic>Parasitology</topic><topic>Peptides</topic><topic>Protein turnover</topic><topic>Proteins</topic><topic>Proteomes</topic><topic>Protozoa</topic><topic>Public health</topic><topic>Research Article</topic><topic>Solutes</topic><topic>Therapeutic targets</topic><topic>Toxicity</topic><topic>Toxoplasma - metabolism</topic><topic>Toxoplasma gondii</topic><topic>Vacuoles - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Piro, Federica</creatorcontrib><creatorcontrib>Masci, Silvia</creatorcontrib><creatorcontrib>Kannan, Geetha</creatorcontrib><creatorcontrib>Focaia, Riccardo</creatorcontrib><creatorcontrib>Schultz, Tracey L</creatorcontrib><creatorcontrib>Thaprawat, Pariyamon</creatorcontrib><creatorcontrib>Carruthers, Vern B</creatorcontrib><creatorcontrib>Di Cristina, Manlio</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Biological Science Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><jtitle>mSphere</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Piro, Federica</au><au>Masci, Silvia</au><au>Kannan, Geetha</au><au>Focaia, Riccardo</au><au>Schultz, Tracey L</au><au>Thaprawat, Pariyamon</au><au>Carruthers, Vern B</au><au>Di Cristina, Manlio</au><au>Blader, Ira J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Toxoplasma gondii putative amino acid transporter localizes to the plant-like vacuolar compartment and controls parasite extracellular survival and stage differentiation</atitle><jtitle>mSphere</jtitle><stitle>mSphere</stitle><addtitle>mSphere</addtitle><date>2024-01-30</date><risdate>2024</risdate><volume>9</volume><issue>1</issue><spage>e0059723</spage><epage>e0059723</epage><pages>e0059723-e0059723</pages><issn>2379-5042</issn><eissn>2379-5042</eissn><abstract>is a protozoan parasite that infects a broad spectrum of hosts and can colonize many organs and cell types. The ability to reside within a wide range of different niches requires substantial adaptability to diverse microenvironments. Very little is known about how this parasite senses various milieus and adapts its metabolism to survive, replicate during the acute stage, and then differentiate to the chronic stage.
possesses a lysosome-like organelle known as the plant-like vacuolar compartment (PLVAC), which serves various functions, including digestion, ion storage and homeostasis, endocytosis, and autophagy. Lysosomes are critical for maintaining cellular health and function by degrading waste materials and recycling components. To supply the cell with the essential building blocks and energy sources required for the maintenance of its functions and structures, the digested solutes generated within the lysosome are transported into the cytosol by proteins embedded in the lysosomal membrane. Currently, a limited number of PLVAC transporters have been characterized, with TgCRT being the sole potential transporter of amino acids and small peptides identified thus far. To bridge this knowledge gap, we used lysosomal amino acid transporters from other organisms as queries to search the
proteome. This led to the identification of four potential amino acid transporters, which we have designated as TgAAT1-4. Assessing their expression and sub-cellular localization, we found that one of them, TgAAT1, localized to the PLVAC and is necessary for normal parasite extracellular survival and bradyzoite differentiation. Moreover, we present preliminary data showing the possible involvement of TgAAT1 in the PLVAC transport of arginine.IMPORTANCE
is a highly successful parasite infecting a broad range of warm-blooded organisms, including about one-third of all humans. Although
infections rarely result in symptomatic disease in individuals with a healthy immune system, the incredibly high number of persons infected, along with the risk of severe infection in immunocompromised patients and the potential link of chronic infection to mental disorders, makes this infection a significant public health concern. As a result, there is a pressing need for new treatment approaches that are both effective and well tolerated. The limitations in understanding how
manages its metabolism to adapt to changing environments and triggers its transformation into bradyzoites have hindered the discovery of vulnerabilities in its metabolic pathways or nutrient acquisition mechanisms to identify new therapeutic targets. In this work, we have shown that the lysosome-like organelle plant-like vacuolar compartment (PLVAC), acting through the putative arginine transporter TgAAT1, plays a pivotal role in regulating the parasite's extracellular survival and differentiation into bradyzoites.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>38051073</pmid><doi>10.1128/msphere.00597-23</doi><tpages>21</tpages><orcidid>https://orcid.org/0000-0003-4154-5210</orcidid><orcidid>https://orcid.org/0000-0001-6859-8895</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Adaptability Amino Acid Transport Systems - metabolism Amino acids Animals Arginine - metabolism Autophagy Bradyzoites Chronic infection Cytosol Endocytosis Homeostasis Humans Hypotheses Immune system Immunocompromised hosts Localization Lysosomes Mental disorders Metabolic pathways Metabolism Microenvironments Parasites Parasitology Peptides Protein turnover Proteins Proteomes Protozoa Public health Research Article Solutes Therapeutic targets Toxicity Toxoplasma - metabolism Toxoplasma gondii Vacuoles - metabolism |
title | A Toxoplasma gondii putative amino acid transporter localizes to the plant-like vacuolar compartment and controls parasite extracellular survival and stage differentiation |
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