{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:39:29Z","timestamp":1785199169013,"version":"3.55.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,7,30]],"date-time":"2024-07-30T00:00:00Z","timestamp":1722297600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000057","name":"HHS | NIH | National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["1P20GM130447-01A1"],"award-info":[{"award-number":["1P20GM130447-01A1"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000060","name":"HHS | NIH | National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["P01A1083211"],"award-info":[{"award-number":["P01A1083211"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSphere"],"published-print":{"date-parts":[[2024,7,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              <jats:italic>Toxoplasma gondii,<\/jats:italic>\n              a widespread parasite, has the ability to infect nearly any nucleated cell in warm-blooded vertebrates. It is estimated that around 2 billion people globally have been infected by this pathogen. Although most healthy individuals can effectively control parasite replication, certain parasites may evade the immune response, establishing cysts in the brain that are refractory to the immune system and resistant to available drugs. For its chronic persistence in the brain, the parasite relies on host cells\u2019 nutrients, particularly amino acids and lipids. Therefore, understanding how latent parasites persist in the brain is crucial for identifying potential drug targets against chronic forms. While shielded within parasitophorous vacuoles (PVs) or cysts,\n              <jats:italic>Toxoplasma<\/jats:italic>\n              exploits the host endoplasmic reticulum (ER) metabolism to sustain its persistence in the brain, resulting in host neurological alterations. In this study, we demonstrate that\n              <jats:italic>T. gondii<\/jats:italic>\n              disrupts the host ER homeostasis, resulting in the accumulation of unfolded protein within the host ER. The host counters this stress by initiating an autophagic pathway known as ER-phagy, which breaks down unfolded proteins into amino acids, promoting their recycling. Our findings unveil the underlying mechanisms employed by\n              <jats:italic>T. gondii<\/jats:italic>\n              to exploit host ER and lysosomal pathways, enhancing nutrient levels during infection. These insights provide new strategies for the treatment of toxoplasmosis.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>\n              Intracellular parasites employ several mechanisms to manipulate the cellular environment, enabling them to persist in the host.\n              <jats:italic>Toxoplasma gondii<\/jats:italic>\n              , a single-celled parasite, possesses the ability to infect virtually any nucleated cell of warm-blooded vertebrates, including nearly 2 billion people worldwide. Unfortunately, existing treatments and immune responses are not entirely effective in eliminating the chronic persisting forms of the parasite. This study reveals that\n              <jats:italic>T. gondii<\/jats:italic>\n              induces the host\u2019s autophagic pathway to boost amino acid levels in infected cells. The depletion of amino acids, in turn, influences the persistence of the parasite\u2019s chronic forms. Significantly, our investigation establishes the crucial role of host endoplasmic reticulum (ER)-phagy in the parasite\u2019s persistence within the host during latent infection.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/msphere.00369-24","type":"journal-article","created":{"date-parts":[[2024,7,9]],"date-time":"2024-07-09T13:00:58Z","timestamp":1720530058000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":9,"title":["Selective host autophagy is induced during the intracellular parasite\n            <i>Toxoplasma gondii<\/i>\n            infection controlling amino acid levels"],"prefix":"10.1128","volume":"9","author":[{"given":"Matthew D.","family":"White","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajendra K.","family":"Angara","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leticia Torres","family":"Dias","sequence":"additional","affiliation":[{"name":"Program in Health Science, University of Santo Amaro (UNISA), S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhananjay D.","family":"Shinde","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7886-0727","authenticated-orcid":true,"given":"Vinai C.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0430-8216","authenticated-orcid":true,"given":"Leonardo","family":"Augusto","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of Nebraska Medical Center, Omaha, Nebraska, USA"},{"name":"Program in Health Science, University of Santo Amaro (UNISA), S\u00e3o Paulo, Brazil"},{"name":"Cognitive Neuroscience of Development &amp; Aging Center, University of Nebraska Medical Center, Omaha, Nebraska, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/encyclopedia2010012"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.abi4343"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","unstructured":"Ferrel A Romano J Panas MW Coppens I Boothroyd JC. 2022. 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