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Adv."],"published-print":{"date-parts":[[2026,1,2]]},"abstract":"<jats:p>\n                    <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                    disrupts the membrane of the\n                    <jats:italic toggle=\"yes\">Mycobacterium<\/jats:italic>\n                    -containing vacuole (MCV) via its EsxA virulence factor, secreted via the ESX-1 system. We identified how pathogenic\n                    <jats:italic toggle=\"yes\">Mycobacterium marinum<\/jats:italic>\n                    exploits host sterol-rich membrane microdomains to induce MCV damage during infection of\n                    <jats:italic toggle=\"yes\">Dictyostelium discoideum<\/jats:italic>\n                    and murine microglial BV-2 cells. Transcriptomic and protein analyses revealed that\n                    <jats:italic toggle=\"yes\">vacuolinC<\/jats:italic>\n                    is specifically induced in response to EsxA-mediated damage. Vacuolins initially associate with the MCV in a patchy distribution, coinciding with sterol-rich microdomain formation before entirely coating the MCV. Functional assays demonstrate that membrane microdomains potentiate\n                    <jats:sc>l<\/jats:sc>\n                    -leucyl\u2013\n                    <jats:sc>l<\/jats:sc>\n                    -leucine methyl ester and EsxA-mediated membrane damage. Knockout of\n                    <jats:italic toggle=\"yes\">vacuolins<\/jats:italic>\n                    and sterol depletion drastically reduce EsxA partitioning into membranes in vitro and decrease MCV damage and Mm escape to the cytosol, thereby substantially impairing Mm intracellular growth and phenocopying in Dd and microglial cells the attenuation of the Mm \u0394RD1 mutant lacking ESX-1. Our results highlight host membrane microdomains as critical platforms exploited by virulent mycobacteria across evolutionary distant host phagocytes, thus representing potential therapeutic targets.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.ady0812","type":"journal-article","created":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T18:58:31Z","timestamp":1767293911000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["Membrane microdomains are crucial for\n                    <i>Mycobacterium marinum<\/i>\n                    EsxA-dependent membrane damage, escape to the cytosol, and infection"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8445-6424","authenticated-orcid":true,"given":"Ang\u00e9lique","family":"Perret","sequence":"first","affiliation":[{"name":"D\u00e9partment de Biochimie, Facult\u00e9 des Sciences, Universit\u00e9 de Gen\u00e8ve, Sciences II, 30 quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9981-5899","authenticated-orcid":true,"given":"Cristina","family":"Bosmani","sequence":"additional","affiliation":[{"name":"D\u00e9partment de Biochimie, Facult\u00e9 des Sciences, Universit\u00e9 de Gen\u00e8ve, Sciences II, 30 quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6340-4318","authenticated-orcid":true,"given":"Florence","family":"Leuba","sequence":"additional","affiliation":[{"name":"D\u00e9partment de Biochimie, Facult\u00e9 des Sciences, Universit\u00e9 de Gen\u00e8ve, Sciences II, 30 quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6020-5356","authenticated-orcid":true,"given":"Krikor","family":"Eblighatian","sequence":"additional","affiliation":[{"name":"D\u00e9partment de Biochimie, Facult\u00e9 des Sciences, Universit\u00e9 de Gen\u00e8ve, Sciences II, 30 quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8992-8686","authenticated-orcid":true,"given":"Aur\u00e9lie","family":"Gu\u00e9ho","sequence":"additional","affiliation":[{"name":"D\u00e9partment de Biochimie, Facult\u00e9 des Sciences, Universit\u00e9 de Gen\u00e8ve, Sciences II, 30 quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7989-610X","authenticated-orcid":true,"given":"Lyudmil","family":"Raykov","sequence":"additional","affiliation":[{"name":"D\u00e9partment de Biochimie, Facult\u00e9 des Sciences, Universit\u00e9 de Gen\u00e8ve, Sciences II, 30 quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3288-5486","authenticated-orcid":true,"given":"Nabil","family":"Hanna","sequence":"additional","affiliation":[{"name":"D\u00e9partment de Biochimie, Facult\u00e9 des Sciences, Universit\u00e9 de Gen\u00e8ve, Sciences II, 30 quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2056-7931","authenticated-orcid":true,"given":"Thierry","family":"Soldati","sequence":"additional","affiliation":[{"name":"D\u00e9partment de Biochimie, Facult\u00e9 des Sciences, Universit\u00e9 de Gen\u00e8ve, Sciences II, 30 quai Ernest Ansermet, CH-1211 Geneva-4, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","unstructured":"World Health Organization Global TB Rep. 2023 (2023); 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