Metabolic interactions: gut microbiome and host-pathogen interactions

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One of the next frontiers of microbial research are metabolic interactions between species. In several collaborative projects we investigate fundamental questions on which metabolites are exchanged between microbes and with the host, and how their own metabolism operates in such consortia.

Specifically we focus on the pathogen Mycobacterium tuberculosis in the context of the TbX project and on natural consortia in food biotechnology. A huge challenge are the complex metabolic interactions in the human gut microbiome (about 1 kg of bacteria) that influence our well being in many ways. In close collaboration with the Macpherson lab at the Inselspital in Bern, we investigate this metabolic handshake between the gut microbiome and gnotobiological mice as well as humans. To this end we employ dynamic stable tracer labeling experiments and a high-throughput metabolomics platform that allows us to detect about 500 metabolites in a given sample per minute. Thus, we go beyond simply counting who is there but venture into what are they doing by focusing on mechanisms and causality.

Scheme of the extensive metabolite exchange between gut microbes and with the host
Scheme of the extensive metabolite exchange between gut microbes and with the host

References

  • Machova I, Snasel J, Zimmermann M, Laibitz D, Plocinski P, Oehlmann W, Singh M, Dostal J, Sauer U, Pichova I (2014). Mycobacterium tuberculosis phosphoenolpyruvate carboxykinase is regulated by redox mechanisms and interaction with thioredoxin. J Biol Chem. 289:13066-78. Pubmed
  • Zimmermann M, Thormann V, Sauer U & Zamboni N (2013). Non-targeted profiling of coenzyme A thioesters in biological samples by tandem mass spectrometry. Anal Chem. 85:8284-90.
  • Watanabe S, Zimmermann M, Goodwin MB, Sauer U, Barry CE 3rd, Boshoff HI (2011). Fumarate reductase activity maintains an energized membrane in anaerobic M. tuberculosis. PLoS Pathogens. 7:e1002287.
  • Rühl M, Hardt WD, Sauer U (2011). Revealing subpopulation specific metabolic pathway usage in mixed cultures by reporter protein-based 13C analysis. Appl Environ Microbiol. 77(5):1816-21. Pubmed

 
 
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16.08.2017
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