{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:14:03Z","timestamp":1790795643953,"version":"4.1.0"},"reference-count":44,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"The Natural Science Fund of China","award":["82472290"],"award-info":[{"award-number":["82472290"]}]},{"name":"The Beijing Public Health Experts Project","award":["G2023-2-002"],"award-info":[{"award-number":["G2023-2-002"]}]},{"name":"The Key Project of Tongzhou District Science and Technology Plan","award":["KJ2024CX061"],"award-info":[{"award-number":["KJ2024CX061"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"published-print":{"date-parts":[[2026,5,19]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Central carbon metabolism is fundamental to the growth and virulence of\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (Mtb). The\n                      <jats:italic toggle=\"yes\">aceE<\/jats:italic>\n                      gene encodes the E1 subunit of the pyruvate dehydrogenase complex that irreversibly converts pyruvate to acetyl-CoA. There, we investigated the impact of\n                      <jats:italic toggle=\"yes\">aceE<\/jats:italic>\n                      inactivation on the physiological metabolism of Mtb. An\n                      <jats:italic toggle=\"yes\">aceE<\/jats:italic>\n                      deletion in Mtb H37Rv was constructed, and the mutant was compared to wild type (WT) by\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      growth assays, colony morphology, biofilm formation, stress tolerance, lipidomics, RNA-seq, and BALB\/c mouse infection. Mtb \u0394\n                      <jats:italic toggle=\"yes\">aceE<\/jats:italic>\n                      exhibited markedly slower planktonic growth, smooth colony morphology, impaired biofilm formation, and was more sensitive to acid, NaNO\n                      <jats:sub>2<\/jats:sub>\n                      , and some commonly used antibiotics. Lipidomics revealed global depletion of mycolic acids and major phospholipids in Mtb \u0394\n                      <jats:italic toggle=\"yes\">aceE<\/jats:italic>\n                      mutant. Transcriptome analysis showed downregulation of TCA cycle and fatty-acid biosynthetic genes. Two weeks after intravenous infection, lung bacillary loads were 0.6 log10 lower for \u0394\n                      <jats:italic toggle=\"yes\">aceE<\/jats:italic>\n                      than in WT, and spleen enlargement was absent, yet the mutant persisted, and pathology was otherwise comparable to WT. AceE is required for robust lipid anabolism, biofilm formation, and maximal growth of Mtb\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      , especially on carbohydrate-based media, but its absence only modestly attenuates acute virulence in mice, underscoring the pathogen\u2019s metabolic plasticity during infection.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        The present study demonstrated that the\n                        <jats:italic toggle=\"yes\">aceE<\/jats:italic>\n                        gene, a crucial enzyme that links glycolysis and the TCA cycle, plays a vital role in regulating the normal physiological metabolism of\n                        <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                        (Mtb). The\n                        <jats:italic toggle=\"yes\">aceE<\/jats:italic>\n                        gene not only aids in the bacteria\u2019s energy metabolism but also promotes lipid synthesis, forming a thicker cell wall that helps Mtb resist various intracellular stresses, further favoring its survival within the host cells. During\n                        <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                        survival, the increased expression of the\n                        <jats:italic toggle=\"yes\">aceE<\/jats:italic>\n                        gene in the virulent Mtb H37Rv strain may enhance the conversion of pyruvate into acetyl-CoA, thereby providing more precursor materials for the synthesis of lipids and amino acids.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.01732-25","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T13:00:40Z","timestamp":1776690040000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["<i>AceE<\/i>\n                    affects the optimum growth and biofilm formation of\n                    <i>Mycobacterium tuberculosis<\/i>\n                    via cell wall lipid remodeling"],"prefix":"10.1128","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2800-1983","authenticated-orcid":true,"given":"Suting","family":"Chen","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jifang","family":"Zheng","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor 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China"]},{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Respiratory and Critical Care Medicine, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Yang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"National Clinical Laboratory on Tuberculosis, Beijing Key Laboratory for Drug-resistant Tuberculosis Research, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengmin","family":"Huo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013xs5b60","id-type":"ROR","asserted-by":"publisher"}],"name":"National Clinical 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