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This is done by utilization of a highly flexible and integrated network of metabolic pathways. Phosphoglucomutase A (\n                      <jats:italic toggle=\"yes\">pgmA<\/jats:italic>\n                      ) is essential for glycogen biosynthesis, which acts as a nutrient reservoir and is known to modulate carbon flux in various pathogens. We, for the first time, investigated the role of\n                      <jats:italic toggle=\"yes\">pgmA<\/jats:italic>\n                      in Mtb by creating a strain lacking this gene. The absence of\n                      <jats:italic toggle=\"yes\">pgmA<\/jats:italic>\n                      hinders the survival of pathogens under nutrient-limiting and reactivation conditions. Our study shows that the lack of cell membrane-associated glycolipids in \u0394\n                      <jats:italic toggle=\"yes\">pgmA<\/jats:italic>\n                      compromises cell wall integrity and increases susceptibility to stress. Interestingly, \u0394\n                      <jats:italic toggle=\"yes\">pgmA<\/jats:italic>\n                      exhibits an enhanced growth phenotype on cholesterol compared to the wild type due to low cyclic adenosine monophosphate (cAMP) levels. Differential gene expression and\n                      <jats:sup>13<\/jats:sup>\n                      C\n                      <jats:sub>3<\/jats:sub>\n                      carbon dilution analyses indicate that stored carbon as glycogen is crucial for Mtb survival under nutrient-limiting conditions. We demonstrate that\n                      <jats:italic toggle=\"yes\">pgmA<\/jats:italic>\n                      is vital for Mtb growth within the host. This study highlights the critical role of\n                      <jats:italic toggle=\"yes\">pgmA<\/jats:italic>\n                      in metabolic adaptation during nutrient starvation and reactivation and its implication on antibiotic and disease persistence. These insights are crucial for developing novel, shorter, and more effective anti-tuberculosis strategies.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        This study for the first time investigated the role of metabolic enzyme phosphoglucomutase A (\n                        <jats:italic toggle=\"yes\">pgmA<\/jats:italic>\n                        ) in\n                        <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                        (Mtb), revealing its crucial functions as a toggle switch between biosynthesis and growth. This work highlights the importance of\n                        <jats:italic toggle=\"yes\">pgmA<\/jats:italic>\n                        in maintaining the metabolic flexibility of Mtb during the nutritional switch. The presence of\n                        <jats:italic toggle=\"yes\">pgmA<\/jats:italic>\n                        is critical for the production of membrane-associated glycolipid, which helps maintain the cell wall integrity under various growth and stress conditions. This adaptability is pivotal for generating starvation-induced antibiotic tolerance in Mtb. In addition to the clinical context, these findings provide a mechanistic foundation for understanding adaptive strategies by Mtb to harsh environments and the development of drug-tolerant bacilli.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/msystems.00420-25","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T09:01:08Z","timestamp":1751274068000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["Phosphoglucomutase A-mediated metabolic adaptation is essential for antibiotic and disease persistence in\n                    <i>Mycobacterium 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