{"id":107371,"date":"2021-05-06T11:12:04","date_gmt":"2021-05-06T15:12:04","guid":{"rendered":"https:\/\/med.virginia.edu\/cell-biology\/?p=107371"},"modified":"2025-05-15T11:15:12","modified_gmt":"2025-05-15T15:15:12","slug":"salmonella-typhimurium-manipulates-macrophage-cholesterol-homeostasis-through-the-ssej-mediated-suppression-of-the-host-cholesterol-transport-protein-abca1","status":"publish","type":"post","link":"https:\/\/med.virginia.edu\/cell-biology\/2021\/05\/06\/salmonella-typhimurium-manipulates-macrophage-cholesterol-homeostasis-through-the-ssej-mediated-suppression-of-the-host-cholesterol-transport-protein-abca1\/","title":{"rendered":"Salmonella Typhimurium manipulates macrophage cholesterol homeostasis through the SseJ-mediated suppression of the host cholesterol transport protein ABCA1"},"content":{"rendered":"<p><strong>UVA Author:<\/strong> James Casanova<br \/>\n<strong>Citation:<\/strong> Greene AR, Owen KA, Casanova JE.Cell Microbiol. 2021 Mar 20:e13329. doi: 10.1111\/cmi.13329. Online ahead of print.PMID: 33742761<\/p>\n<p><strong>DOI:<\/strong> <a>https:\/\/pubmed.ncbi.nlm.nih.gov\/33742761\/<\/a><br \/>\n<strong>Pub-Med Number<\/strong>: 33742761<\/p>\n<hr \/>\n<p>Upon infection of host cells, Salmonella enterica serovar Typhimurium resides in a modified-endosomal compartment referred to as the Salmonella-containing vacuole (SCV). SCV biogenesis is driven by multiple effector proteins translocated through two type III secretion systems (T3SS-1 and T3SS-2). While many host proteins targeted by these effector proteins have been characterised, the role of host lipids in SCV dynamics remains poorly understood. Previous studies have shown that S. Typhimurium infection in macrophages leads to accumulation of intracellular cholesterol, some of which concentrates in and around SCVs; however, the underlying mechanisms remain unknown. Here, we show that S. Typhimurium utilises the T3SS-2 effector SseJ to downregulate expression of the host cholesterol transporter ABCA1 in macrophages, leading to a ~45% increase in cellular cholesterol. Mechanistically, SseJ activates a signalling cascade involving the host kinases FAK and Akt to suppress Abca1 expression. Mutational inactivation of SseJ acyltransferase activity, silencing FAK, or inhibiting Akt prevents Abca1 downregulation and the corresponding accumulation of cholesterol during infection. Importantly, RNAi-mediated silencing of ABCA1 rescued bacterial survival in FAK-deficient macrophages, suggesting that Abca1 downregulation and cholesterol accumulation are important for intracellular survival.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>UVA Author: James Casanova Citation: Greene AR, Owen KA, Casanova JE.Cell Microbiol. 2021 Mar 20:e13329. doi: 10.1111\/cmi.13329. Online ahead of print.PMID: 33742761 DOI: https:\/\/pubmed.ncbi.nlm.nih.gov\/33742761\/ Pub-Med Number: 33742761 Upon infection of host cells, Salmonella enterica serovar Typhimurium resides in a modified-endosomal compartment referred to as the Salmonella-containing vacuole (SCV). SCV biogenesis is driven by multiple effector [&hellip;]<\/p>\n","protected":false},"author":1740,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":"","_links_to":"","_links_to_target":""},"categories":[13],"tags":[],"class_list":["post-107371","post","type-post","status-publish","format-standard","hentry","category-featured-publications"],"acf":false,"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.1.1 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Salmonella Typhimurium manipulates macrophage cholesterol homeostasis through the SseJ-mediated suppression of the host cholesterol transport protein ABCA1 - 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\/2021\/05\/06\/salmonella-typhimurium-manipulates-macrophage-cholesterol-homeostasis-through-the-ssej-mediated-suppression-of-the-host-cholesterol-transport-protein-abca1\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Salmonella Typhimurium manipulates macrophage cholesterol homeostasis through the SseJ-mediated suppression of the host cholesterol transport protein ABCA1 - Department of Cell Biology\" \/>\n<meta property=\"og:description\" content=\"UVA Author: James Casanova Citation: Greene AR, Owen KA, Casanova JE.Cell Microbiol. 2021 Mar 20:e13329. doi: 10.1111\/cmi.13329. Online ahead of print.PMID: 33742761 DOI: https:\/\/pubmed.ncbi.nlm.nih.gov\/33742761\/ Pub-Med Number: 33742761 Upon infection of host cells, Salmonella enterica serovar Typhimurium resides in a modified-endosomal compartment referred to as the Salmonella-containing vacuole (SCV). SCV biogenesis is driven by multiple effector [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/med.virginia.edu\/cell-biology\/2021\/05\/06\/salmonella-typhimurium-manipulates-macrophage-cholesterol-homeostasis-through-the-ssej-mediated-suppression-of-the-host-cholesterol-transport-protein-abca1\/\" \/>\n<meta property=\"og:site_name\" content=\"Department of Cell Biology\" \/>\n<meta property=\"article:published_time\" content=\"2021-05-06T15:12:04+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2025-05-15T15:15:12+00:00\" \/>\n<meta name=\"author\" content=\"zkr7e@virginia.edu\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"zkr7e@virginia.edu\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"1 minute\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/med.virginia.edu\/cell-biology\/2021\/05\/06\/salmonella-typhimurium-manipulates-macrophage-cholesterol-homeostasis-through-the-ssej-mediated-suppression-of-the-host-cholesterol-transport-protein-abca1\/\",\"url\":\"https:\/\/med.virginia.edu\/cell-biology\/2021\/05\/06\/salmonella-typhimurium-manipulates-macrophage-cholesterol-homeostasis-through-the-ssej-mediated-suppression-of-the-host-cholesterol-transport-protein-abca1\/\",\"name\":\"Salmonella Typhimurium manipulates macrophage cholesterol homeostasis through the SseJ-mediated suppression of the host cholesterol transport protein ABCA1 - 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