Abstract:
:An organism's metabolic activity leaves an extracellular footprint and dynamic changes in this exometabolome inform about nutrient uptake, waste disposal and signalling activities. Using non-targeted mass spectrometry, we report exometabolome dynamics of hypoxia-induced, non-replicating mycobacteria that are thought to play a role in latent tuberculosis. Despite evidence of active metabolism, little is known about the mechanisms enabling obligate aerobic mycobacteria to cope with hypoxia, resulting in long-term survival and increased chemotherapeutic tolerance. The dynamics of 379 extracellular compounds of Mycobacterium smegmatis were deconvoluted with a genome-scale metabolic reaction-pair network to generate hypotheses about intracellular pathway usage. Time-resolved (13) C-tracing and mutant experiments then demonstrated a crucial, energy-generating role of asparagine utilization and non-generic usage of the glyoxylate shunt for hypoxic fitness. Experiments with M. bovis and M. tuberculosis revealed the general relevance of asparagine fermentation and a variable contribution of the glyoxylate shunt to non-replicative, hypoxic survival between the three species.
journal_name
Environ Microbioljournal_title
Environmental microbiologyauthors
Zimmermann M,Kuehne A,Boshoff HI,Barry CE 3rd,Zamboni N,Sauer Udoi
10.1111/1462-2920.13056subject
Has Abstractpub_date
2015-11-01 00:00:00pages
4802-15issue
11eissn
1462-2912issn
1462-2920journal_volume
17pub_type
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