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Drug efficacy varies depending on inoculum and the timing of treatment initiation. These differences reflect, in part, physiological adaptations of\n                      <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                      (\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      ) to host immune pressure. We used novel molecular markers of pathogen health (RS ratio and SEARCH-TB) to contrast\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      phenotypes in the BALB\/c high dose aerosol (HDA) subacute TB and low dose aerosol (LDA) chronic TB infection models, focusing on the onset of adaptive immunity. 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The HDA model is shown to be a mixed model, spanning immune phases with initial treatment acting on replicating bacteria and later treatment acting on immune-constrained populations. Together, the two models offer complementary perspectives on therapeutic activity across the spectrum of bacterial states and provide a framework for designing regimens that are effective against both active and immune-constrained\n                      <jats:italic toggle=\"yes\">Mtb<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/aac.00421-26","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:00:10Z","timestamp":1785506410000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Adaptive immunity shapes baseline physiology of\n                    <i>M. tuberculosis<\/i>\n                    in high-dose versus low-dose infection BALB\/c mouse drug treatment 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