{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:42:40Z","timestamp":1791988960268,"version":"4.4.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,11,5]],"date-time":"2024-11-05T00:00:00Z","timestamp":1730764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,11,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              The VII secretion system is the main channel for\n              <jats:italic>Mycobacterium tuberculosis<\/jats:italic>\n              (\n              <jats:italic>MTB<\/jats:italic>\n              ) to secrete virulence proteins. The ESAT-like proteins EsxA\/B and EsxW\/V in the RD region of its genome have been used as targets for vaccine antigens. However, the function of EsxO\/P has not been explored, although it was predicted to potentially induce Th1 cell responses as a vaccine development target. In this study, the VII secretion system effector molecule Rv2347c was heterologously expressed in\n              <jats:italic>Mycobacterium smegmatis<\/jats:italic>\n              and found to inhibit the expression of the early marker RAB5 of phagosomes, thus preventing the maturation process of phagosomes toward lysosomes, and activated the host cytoplasmic sensing pathway. It inhibited autophagy and activated IFN\u03b2 transcription through the STING\/TBK1 pathway promoting the host\u2019s survival. Therefore, Rv2347c plays an important role in the pathogenesis of\n              <jats:italic>MTB<\/jats:italic>\n              with the potential to be utilized as a new target for tuberculosis vaccine development.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>IMPORTANCE<\/jats:title>\n            <jats:p>We found that the ESAT-like protein Rv2347c (EsxP) can inhibit the maturation of phagosomes, leading to mycobacterium escape from phagosomes into the cytoplasm, which triggers the host\u2019s cytoplasmic sensing pathway STING\/TBK1, inhibiting autophagy and upregulating IFN\u03b2 transcription, which contributes to the survival of mycobacterium in the host cell. We also found that Rv2347c was able to activate host immunity by activating NF-\u03baB via STING and promoting the transcription of downstream pro-inflammatory factors. Meanwhile, the host also produces IL-1\u03b2 to repair phagosome maturation arrest via the STING-mediated non-NF-\u03baB pathway.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.01188-24","type":"journal-article","created":{"date-parts":[[2024,9,23]],"date-time":"2024-09-23T23:38:07Z","timestamp":1727134687000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["<i>Mycobacterium tuberculosis<\/i>\n            VII secretion system effector molecule Rv2347c blocks the maturation of phagosomes and activates the STING\/TBK1 signaling pathway to inhibit cell autophagy"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-5255-3667","authenticated-orcid":false,"given":"Zhiyong","family":"Jiang","sequence":"first","affiliation":[{"name":"Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Environment and Bio-Resource of the Three Gorges Area, 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