Systems analysis reveals alternate metabolic states adopted by Mycobacterium tuberculosis across species

Mycobacterium tuberculosis (Mtb) persists within macrophages, yet how different host species shape bacterial state remains poorly understood. Here, we directly compared the intracellular transcriptome of Mtb during infection of human and mouse macrophages, revealing distinct host-imposed microenvironments that drive the pathogen into separable metabolic states. Lipid metabolism and regulatory circuits were prominently remodeled, with mouse macrophages inducing iron- and oxidative-stress responses while human macrophages promoted fatty acid import programs.