{"id":107621,"date":"2025-01-01T14:52:31","date_gmt":"2025-01-01T19:52:31","guid":{"rendered":"https:\/\/med.virginia.edu\/cell-biology\/?p=107621"},"modified":"2026-05-22T17:01:07","modified_gmt":"2026-05-22T21:01:07","slug":"salmonella-induced-cholesterol-accumulation-in-infected-macrophages-suppresses-autophagy-via-mtorc1-activation","status":"publish","type":"post","link":"https:\/\/med.virginia.edu\/cell-biology\/2025\/01\/01\/salmonella-induced-cholesterol-accumulation-in-infected-macrophages-suppresses-autophagy-via-mtorc1-activation\/","title":{"rendered":"Salmonella-induced cholesterol accumulation in infected macrophages suppresses autophagy via mTORC1 activation"},"content":{"rendered":"<p><strong>Authors:<\/strong> <span class=\"authors-list-item \"><a class=\"full-name\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Torsilieri+HM&amp;cauthor_id=39602284\" data-ga-category=\"search\" data-ga-action=\"author_link\" data-ga-label=\"Holly M Torsilieri\">Holly M Torsilieri<\/a><sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span><a class=\"affiliation-link\" title=\"Department of Microbiology, Immunology, and Cancer Biology, University of Virginia School of Medicine, Charlottesville, VA 22903.\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39602284\/#full-view-affiliation-1\">1<\/a><span class=\"author-sup-separator\">\u00a0<\/span><a class=\"affiliation-link\" title=\"Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA 22903.\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39602284\/#full-view-affiliation-2\">2<\/a><\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \"><a class=\"full-name\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Upchurch+CM&amp;cauthor_id=39602284\" data-ga-category=\"search\" data-ga-action=\"author_link\" data-ga-label=\"Clint M Upchurch\">Clint M Upchurch<\/a><sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span><a class=\"affiliation-link\" title=\"Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22903.\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39602284\/#full-view-affiliation-3\">3<\/a><\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \"><a class=\"full-name\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Leitinger+N&amp;cauthor_id=39602284\" data-ga-category=\"search\" data-ga-action=\"author_link\" data-ga-label=\"Norbert Leitinger\">Norbert Leitinger<\/a><sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span><a class=\"affiliation-link\" title=\"Department of Pharmacology, University of Virginia School of Medicine, Charlottesville, VA 22903.\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/39602284\/#full-view-affiliation-3\">3<\/a><\/sup><span class=\"comma\">,\u00a0<\/span><\/span><span class=\"authors-list-item \"><a class=\"full-name\" href=\"https:\/\/pubmed.ncbi.nlm.nih.gov\/?sort=date&amp;term=Casanova+JE&amp;cauthor_id=39602284\" data-ga-category=\"search\" data-ga-action=\"author_link\" data-ga-label=\"James E Casanova\">James E Casanova<\/a><sup class=\"affiliation-links\"><span class=\"author-sup-separator\">\u00a0<\/span><\/sup><\/span><\/p>\n<p><strong>Citation:<\/strong> Torsilieri HM, Upchurch CM, Leitinger N, Casanova JE.\u00a0<i>Salmonella<\/i>-induced cholesterol accumulation in infected macrophages suppresses autophagy via mTORC1 activation. Mol Biol Cell. 2025 Jan 1;36(1):ar3. doi: 10.1091\/mbc.E24-06-0283. Epub 2024 Nov 27. PMID: 39602284; PMCID: PMC11742112.<\/p>\n<p><strong>DOI: <\/strong>10.1091\/mbc.E24-06-0283<\/p>\n<p><strong>Pub-Med Number<\/strong>: 39602284<\/p>\n<hr \/>\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\n<div id=\"abstract\" class=\"abstract\">\n<div id=\"eng-abstract\" class=\"abstract-content selected\">\n<p><i>Salmonella enterica<\/i>\u00a0serovar Typhimurium is a Gram-negative bacillus that infects the host intestinal epithelium and resident macrophages. Many intracellular pathogens induce an autophagic response in host cells but have evolved mechanisms to subvert that response. Autophagy is closely linked to cellular cholesterol levels; mTORC1 senses increased cholesterol in lysosomal membranes, leading to its hyperactivity and suppression of autophagy. Previous studies indicate that\u00a0<i>Salmonella<\/i>\u00a0infection induces dramatic accumulation of cholesterol in macrophages, a fraction of which localizes to\u00a0<i>Salmonella<\/i>\u00a0containing vacuoles (SCVs). We previously reported that the bacterial effector protein SseJ triggers cholesterol accumulation through a signaling cascade involving focal adhesion kinase (FAK) and Akt. Here we show that mTORC1 is recruited to SCVs and is hyperactivated in a cholesterol-dependent manner. If cholesterol accumulation is prevented pharmacologically or through mutation of\u00a0<i>sseJ<\/i>, autophagy is induced and bacterial survival is attenuated. Notably, the host lipid transfer protein OSBP (oxysterol binding protein 1) is also recruited to SCVs and its activity is necessary for both cholesterol transfer to SCVs and mTORC1 activation during infection. Finally, lipidomic analysis of\u00a0<i>Salmonella<\/i>-infected macrophages revealed new insights into how\u00a0<i>Salmonella<\/i>\u00a0may manipulate lipid homeostasis to benefit its survival. We propose that\u00a0<i>S.<\/i>\u00a0Typhimurium induces cholesterol accumulation through SseJ to activate mTORC1, preventing autophagic clearance of bacteria.<\/p>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Authors: Holly M Torsilieri\u00a01\u00a02,\u00a0Clint M Upchurch\u00a03,\u00a0Norbert Leitinger\u00a03,\u00a0James E Casanova\u00a0 Citation: Torsilieri HM, Upchurch CM, Leitinger N, Casanova JE.\u00a0Salmonella-induced cholesterol accumulation in infected macrophages suppresses autophagy via mTORC1 activation. Mol Biol Cell. 2025 Jan 1;36(1):ar3. doi: 10.1091\/mbc.E24-06-0283. Epub 2024 Nov 27. PMID: 39602284; PMCID: PMC11742112. DOI: 10.1091\/mbc.E24-06-0283 Pub-Med Number: 39602284 Salmonella enterica\u00a0serovar Typhimurium is a Gram-negative [&hellip;]<\/p>\n","protected":false},"author":1740,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[13],"tags":[22],"class_list":["post-107621","post","type-post","status-publish","format-standard","hentry","category-featured-publications","tag-intranet"],"acf":false,"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.4 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Salmonella-induced cholesterol accumulation in infected macrophages suppresses autophagy via mTORC1 activation - Department of Cell Biology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/med.virginia.edu\/cell-biology\/2025\/01\/01\/salmonella-induced-cholesterol-accumulation-in-infected-macrophages-suppresses-autophagy-via-mtorc1-activation\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Salmonella-induced cholesterol accumulation in infected macrophages suppresses autophagy via mTORC1 activation - Department of Cell Biology\" \/>\n<meta property=\"og:description\" content=\"Authors: Holly M Torsilieri\u00a01\u00a02,\u00a0Clint M Upchurch\u00a03,\u00a0Norbert Leitinger\u00a03,\u00a0James E Casanova\u00a0 Citation: Torsilieri HM, Upchurch CM, Leitinger N, Casanova JE.\u00a0Salmonella-induced cholesterol accumulation in infected macrophages suppresses autophagy via mTORC1 activation. Mol Biol Cell. 2025 Jan 1;36(1):ar3. doi: 10.1091\/mbc.E24-06-0283. Epub 2024 Nov 27. PMID: 39602284; PMCID: PMC11742112. 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