{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T05:23:30Z","timestamp":1777440210177,"version":"3.51.4"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T00:00:00Z","timestamp":1704931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Coxiella burnetii<\/jats:italic> is an obligate intracellular bacterium that causes Q fever, a zoonotic disease typically manifests as a severe flu-illness. After invading into the host cells, <jats:italic>C. burnetii<\/jats:italic> delivers effectors to regulate the vesicle trafficking and fusion events to form a large and mature <jats:italic>Coxiella<\/jats:italic>-containing vacuole (CCV), providing sufficient space and nutrition for its intracellular growth and proliferation. Lysosomal trafficking regulator (LYST) is a member of the Beige and Chediak-Higashi syndrome (BEACH) family, which regulates the transport of vesicles to lysosomes and regulates TLR signaling pathway, but the effect of LYST on <jats:italic>C. burnetii<\/jats:italic> infection is unclear. In this study, a series of experiments has been conducted to investigate the influence of LYST on intracellular growth of <jats:italic>C. burnetii<\/jats:italic>. Our results showed that <jats:italic>lyst<\/jats:italic> transcription was up-regulated in the host cells after <jats:italic>C. burnetii<\/jats:italic> infection, but there is no significant change in <jats:italic>lyst<\/jats:italic> expression level after infection with the Dot\/Icm type IV secretion system (T4SS) mutant strain, while CCVs expansion and significantly increasing load of <jats:italic>C. burnetii<\/jats:italic> appeared in the host cells with a silenced <jats:italic>lyst<\/jats:italic> gene, suggesting LYST inhibits the intracellular proliferation of <jats:italic>C. burnetii<\/jats:italic> by reducing CCVs size. Then, the size of CCVs and the load of <jats:italic>C. burnetii<\/jats:italic> in the HeLa cells pretreated with E-64d were significantly decreased. In addition, the level of iNOS was decreased significantly in LYST knockout THP-1 cells, which was conducive to the intracellular replication of <jats:italic>C. burnetii<\/jats:italic>. This data is consistent with the phenotype of L-NMMA-treated THP-1 cells infected with <jats:italic>C. burnetii<\/jats:italic>. Our results revealed that the upregulation of <jats:italic>lyst<\/jats:italic> transcription after infection is due to effector secretion of <jats:italic>C. burnetii<\/jats:italic> and LYST inhibit the intracellular replication of <jats:italic>C. burnetii<\/jats:italic> by reducing the size of CCVs and inducing <jats:italic>nos2<\/jats:italic> expression.<\/jats:p>","DOI":"10.3389\/fcimb.2023.1336600","type":"journal-article","created":{"date-parts":[[2024,1,11]],"date-time":"2024-01-11T05:22:30Z","timestamp":1704950550000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Lysosomal trafficking regulator restricts intracellular growth of Coxiella burnetii by inhibiting the expansion of Coxiella-containing vacuole and upregulating nos2 expression"],"prefix":"10.3389","volume":"13","author":[{"given":"Weiqiang","family":"Wan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingliang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"OuYang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghui","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolu","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ning","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/382262a0","article-title":"Identification of the homologous beige and Chediak\u2013Higashi syndrome genes","volume":"382","author":"Barbosa","year":"1996","journal-title":"Nature"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00175-11","article-title":"Dot\/Icm type IVB secretion system requirements for coxiella burnetii growth in human macrophages","volume":"2","author":"Beare","year":"2011","journal-title":"mBio"},{"key":"B3","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1016\/j.tim.2018.12.012","article-title":"Nutrition and bipartite metabolism of intracellular pathogens","volume":"27","author":"Best","year":"2019","journal-title":"Trends Microbiol."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000179","article-title":"Control of parasitophorous vacuole expansion by LYST\/beige restricts the intracellular growth of leishmania amazonensis","volume":"4","author":"Beverley","year":"2008","journal-title":"PloS Pathog."},{"key":"B5","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1016\/j.it.2015.01.003","article-title":"Nitric oxide synthase in innate and adaptive immunity: an update","volume":"36","author":"Bogdan","year":"2015","journal-title":"Trends Immunol."},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3791\/52851","article-title":"Generation and multi-phenotypic high-content screening of coxiella burnetii transposon mutants","author":"Bonazzi","year":"2015","journal-title":"J. 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