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Adv."],"published-print":{"date-parts":[[2026,2,13]]},"abstract":"<jats:p>\n                    Here, we have used a comprehensive, system-wide approach to delineate the function of the virulence-associated proteins B and C 36 (VapBC36) toxin-antitoxin (TA) system in\n                    <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                    pathophysiology. We show that VapC36 interacts with cognate and noncognate antitoxins. We demonstrate that\n                    <jats:italic toggle=\"yes\">serX<\/jats:italic>\n                    is degraded in vitro by VapC36. We show that VapC36 binds copper, which enhances its ribonuclease activity. Furthermore, we report that deletion of\n                    <jats:italic toggle=\"yes\">vapBC36<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">vapC36<\/jats:italic>\n                    enhances the susceptibility of\n                    <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                    upon exposure to copper in vitro. Compared to the wild-type strain, \u0394\n                    <jats:italic toggle=\"yes\">BC36<\/jats:italic>\n                    was attenuated for growth in guinea pigs. However, deletion of either\n                    <jats:italic toggle=\"yes\">vapC36<\/jats:italic>\n                    or\n                    <jats:italic toggle=\"yes\">vapBC36<\/jats:italic>\n                    did not affect\n                    <jats:italic toggle=\"yes\">M. tuberculosis<\/jats:italic>\n                    growth in mice. Compared to the wild-type strain, the in vivo susceptibility of \u0394\n                    <jats:italic toggle=\"yes\">C36 and<\/jats:italic>\n                    \u0394\n                    <jats:italic toggle=\"yes\">BC36<\/jats:italic>\n                    strains was increased in copper-fed mice. Together, these findings have enhanced our understanding of the regulation and contribution of TA systems in mycobacterial pathophysiology.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adw7134","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T18:58:47Z","timestamp":1770836327000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":6,"title":["VapC36-mediated intrinsic stress adaption is required for copper tolerance and pathogenesis of\n                    <i>Mycobacterium tuberculosis<\/i>"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4491-8732","authenticated-orcid":true,"given":"Arun","family":"Sharma","sequence":"first","affiliation":[{"name":"BRIC-Translational Health Science and Technology Institute, Faridabad-Gurugram expressway, Faridabad, Haryana, 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