Dynamic exometabolome analysis reveals active metabolic pathways in non-replicating mycobacteria

摘要: An organism's metabolic activity leaves an extracellular footprint and dynamic changes in this exometabolome inform about nutrient uptake, waste disposal signalling activities. Using non-targeted mass spectrometry, we report dynamics of hypoxia-induced, non-replicating mycobacteria that are thought to play a role latent tuberculosis. Despite evidence active metabolism, little is known the mechanisms enabling obligate aerobic cope with hypoxia, resulting long-term survival increased chemotherapeutic tolerance. The 379 compounds Mycobacterium smegmatis were deconvoluted genome-scale reaction-pair network generate hypotheses intracellular pathway usage. Time-resolved (13) C-tracing mutant experiments then demonstrated crucial, energy-generating asparagine utilization non-generic usage glyoxylate shunt for hypoxic fitness. Experiments M. bovis M. tuberculosis revealed general relevance fermentation variable contribution non-replicative, between three species.