Metabolomics of Mycobacterium tuberculosis Reveals Compartmentalized Co-Catabolism of Carbon Substrates

Metabolic adaptation to the host environment is a defining feature of the pathogenicity of Mycobacterium tuberculosis (Mtb), but we lack biochemical knowledge of its metabolic networks Many bacteria use catabolite repression as a regulatory mechanism to maximize growth by consuming individual carbon substrates in a preferred sequence and growing with diauxic kinetics Surprisingly, untargeted metabolite profiling of Mtb growing on C-13-labeled carbon substrates revealed that Mtb could catabolize multiple carbon sources simultaneously to achieve enhanced monophasic growth Moreover, when co-catabolizing multiple carbon sources, Mtb differentially catabolized each carbon source through the glycolytic, pentose phosphate, and/or tricarboxylic acid pathways to distinct metabolic fates This unusual topologic organization of bacterial intermediary metabolism has not been previously observed and may subserve the pathogenicity of Mtb