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Management of pulmonary tuberculosis requires at least 6 months of combination therapy for susceptible cases (and considerably longer in cases with drug resistance or intolerance). Developing shorter, more efficient regimens not prone to relapse requires a better understanding of the various phenotypic subpopulations of M. tuberculosis (MTB) that emerge in different microenvironments in vivo — and the distinct responses of these subpopulations to antibiotics. Walter et al. utilized a murine model of pulmonary tuberculosis to evaluate differences in number of colony-forming units (CFU, a measure of bacterial burden) and rRNA synthesis profiles (RS ratio, a proxy for MTB replication) among pathogens found in various host microenvironments, in…