{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T15:10:29Z","timestamp":1788793829660,"version":"build-2803163510"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"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>\n                    <jats:italic>Coxiella burnetii<\/jats:italic>\n                    is a Gram-negative, obligate intracellular pathogen and the causative agent of the zoonotic disease Q fever. Resident alveolar macrophages are the first target cells, but\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    spreads to other cell types. While we have information about\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    uptake and the establishment of the replication-competent phagolysosomal-like\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    -containing vacuole (CCV), it is not well studied how\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    exits its host cell. Here, we show that an infection with\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    also triggers the activation of TFEB, a master regulator of autophagy and lysosomal development. The activation occurs in a time-dependent manner and depends on the size of the CCV. Crucially, TFEB activation during\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    infection depends on MCOLN1, which channels Ca\n                    <jats:sup>2+<\/jats:sup>\n                    across the lysosomal membrane into the cytosol. Knock-down of MCOLN1 resulted in reduced TFEB activation and smaller CCVs, while MCOLN1 activation boosted bacterial egress. Indeed, peripheral CCVs are positive for LAMP1\/2 and release bacteria, without inducing host cell death. Importantly, LAMP1\/2 and\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    were stainable in non-permeabilized cells at sites of bacterial release, demonstrating fusion of the lysosome with the plasma membrane. Crucially, while replication of\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    is not inhibited in cells lacking LAMP1\/2, egress is impaired. Taken together, our data indicates that with increasing CCV size, TFEB is activated by the release of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    from lysosomes via the MCOLN1 channel, which in turn enables further CCV development and damage of the CCV membrane. This triggers lysosomal exocytosis and egress of\n                    <jats:italic>C. burnetii<\/jats:italic>\n                    without cell death induction.\n                  <\/jats:p>","DOI":"10.3389\/fcimb.2026.1835140","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:22:51Z","timestamp":1786681371000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["TFEB and MCOLN1 are important for Coxiella burnetii egress via lysosomal exocytosis"],"prefix":"10.3389","volume":"16","author":[{"given":"Sven","family":"Rinkel","sequence":"first","affiliation":[{"name":"Mikrobiologisches Institut, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Schulze-Luehrmann","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhavyalakshmi","family":"Kadavil Baburaj","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiona","family":"Weber","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth M.","family":"Liebler-Tenorio","sequence":"additional","affiliation":[{"name":"Friedrich-Loeffler-Institut, Institut f\u00fcr Molekulare Pathogenese","place":["Jena, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"L\u00fchrmann","sequence":"additional","affiliation":[{"name":"Mikrobiologisches Institut, Universit\u00e4tsklinikum Erlangen, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","place":["Erlangen, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1186\/1751-0147-55-13","article-title":"Coxiella burnetii associated reproductive disorders in domestic animals--a critical review","volume":"55","author":"Agerholm","year":"2013","journal-title":"Acta Vet. 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