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Chem Biol. 2010 Oct 29;17(10):1122-31. doi: 10.1016/j.chembiol.2010.08.009.

Metabolomics of Mycobacterium tuberculosis reveals compartmentalized co-catabolism of carbon substrates.

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1
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, USA.

Abstract

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 ¹³C-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.

PMID:
21035735
DOI:
10.1016/j.chembiol.2010.08.009
[Indexed for MEDLINE]
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