{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:53:07Z","timestamp":1785433987435,"version":"3.56.0"},"reference-count":84,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T00:00:00Z","timestamp":1773187200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21AI125475, R21AI163580"],"award-info":[{"award-number":["R21AI125475, R21AI163580"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI175106"],"award-info":[{"award-number":["R01AI175106"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UMN | Office of the Vice President for Research, University of Minnesota","award":["Bridge Award"],"award-info":[{"award-number":["Bridge Award"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,3,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      uses several ESX type VII protein secretion systems for pathogenesis.\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      ESX-5 is only partially characterized because it is essential for growth in standard lab culture conditions. To circumvent ESX-5 essentiality, we made an\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      strain in which the central ESX-5 membrane component EccD\n                      <jats:sub>5<\/jats:sub>\n                      can be conditionally depleted. Here, we use this strain to demonstrate that\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      requires the ESX-5 secretion system to grow using specific carbon sources\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      , to grow in cultured macrophages, and to replicate and disseminate in aerosol-infected mice.\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      requires ESX-5 to use glycerol or glucose as the sole carbon source. Use of glycerol and glucose also depends on the outer membrane protein PPE51. We show that\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      requires ESX-5 activity for outer membrane export and surface exposure of PPE51. Expression of the outer membrane porin MspA enabled growth of ESX-5-deficient\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      on glycerol, suggesting that the main function of ESX-5\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      is to export nutrient transporters to the outer membrane. Depletion of EccD\n                      <jats:sub>5<\/jats:sub>\n                      in acutely infected mice caused clearance of\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      from lung tissues, demonstrating the critical importance of ESX-5 activity during infection. Our findings suggest that ESX-5 promotes\n                      <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                      pathogenesis by mediating export of outer membrane proteins that enable nutrient acquisition.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                        ESX type VII secretion systems play important roles in pathogenesis, but the functions of ESX-5 are not well characterized because it is essential for growth in standard lab culture conditions. We used a strain that conditionally expresses a central membrane component of the ESX-5 secretion apparatus to determine how ESX-5 impacts growth in lab cultures and in a mouse infection model. We found that\n                        <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                        requires ESX-5 to grow using several carbon sources and to grow in the lungs of infected mice. Inhibiting production of the ESX-5 secretion system in mice also led to clearance of\n                        <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                        from lung tissues. Our results demonstrate that the\n                        <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                        ESX-5 system is a critical virulence factor and suggest that ESX-5 is a strong candidate for antitubercular drug development.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.03500-25","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T21:02:12Z","timestamp":1769806932000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["The\n                    <i>Mycobacterium tuberculosis<\/i>\n                    ESX-5 secretion system enables carbon source utilization and growth in mice"],"prefix":"10.1128","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0987-9181","authenticated-orcid":false,"given":"Alisha 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