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Previous \u201comics\u201d studies highlighted the role MTP potentially plays in\n                      <jats:italic>Mtb<\/jats:italic>\n                      central carbon metabolism (CCM). However, its precise contribution to metabolism remains unknown.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      This study aimed to examine the role of MTP in the bioenergetic metabolism of\n                      <jats:italic>Mtb<\/jats:italic>\n                      , using bedaquiline (BDQ) to inhibit ATP production through oxidative phosphorylation (OXPHOS), extracellular flux analysis,\n                      <jats:italic>Mtb<\/jats:italic>\n                      wildtype (WT), \u2206\n                      <jats:italic>mtp<\/jats:italic>\n                      deletion mutant, and\n                      <jats:italic>mtp-<\/jats:italic>\n                      complemented strains. The role of MTP in regulation of CCM was assessed using\n                      <jats:sup>13<\/jats:sup>\n                      C\n                      <jats:sub>6<\/jats:sub>\n                      -metabolic flux analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      MTP was associated with increased bacterial respiration and decreased carbon catabolism via glycolysis in response to the inhibition of ATP synthase by BDQ. The dependence of\n                      <jats:italic>Mtb<\/jats:italic>\n                      \u0394\n                      <jats:italic>mtp<\/jats:italic>\n                      on OXPHOS for energy production was demonstrated to be greater than the WT and\n                      <jats:italic>mtp-<\/jats:italic>\n                      complemented strains. In addition, metabolic flux profiles revealed that in the \u0394\n                      <jats:italic>mtp<\/jats:italic>\n                      mutant, CCM was dysregulated by decreasing flux through glycolysis, tricarboxylic acid cycle, glyoxylate and dicarboxylate metabolism, and the pentose phosphate pathway in comparison to the WT.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These novel findings show that MTP is associated with the regulation of bioenergetics and metabolism pathways and substantiate MTP as a potential biomarker for TB diagnostics\/therapeutics, and a novel target for vaccine\/drug development.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s11306-025-02320-5","type":"journal-article","created":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T13:01:21Z","timestamp":1755003681000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mycobacterium tuberculosis curli pili facilitates pathogenicity by modulating central carbon metabolism"],"prefix":"10.1007","volume":"21","author":[{"given":"Tarien J.","family":"Naidoo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinese","family":"Ashokcoomar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry","family":"Truebody","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jared S.","family":"Mackenzie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrie J. 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