Triosephosphate isomerase is dispensable in vitro yet essential for Mycobacterium tuberculosis to establish infection

Trujillo, Carolina, Blumenthal, Antje, Marrero, Joeli, Rhee, Kyu Y., Schnappinger, Dirk and Ehrt, Sabine (2014) Triosephosphate isomerase is dispensable in vitro yet essential for Mycobacterium tuberculosis to establish infection. mBio, 5 2: e00085-14.1-e00085-14.12. doi:10.1128/mBio.00085-14


Author Trujillo, Carolina
Blumenthal, Antje
Marrero, Joeli
Rhee, Kyu Y.
Schnappinger, Dirk
Ehrt, Sabine
Title Triosephosphate isomerase is dispensable in vitro yet essential for Mycobacterium tuberculosis to establish infection
Formatted title
Triosephosphate isomerase is dispensable in vitro yet essential for Mycobacterium tuberculosis to establish infection
Journal name mBio   Check publisher's open access policy
ISSN 2161-2129
2150-7511
Publication date 2014-04-22
Sub-type Article (original research)
DOI 10.1128/mBio.00085-14
Open Access Status DOI
Volume 5
Issue 2
Start page e00085-14.1
End page e00085-14.12
Total pages 12
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Formatted abstract
Triosephosphate isomerase (TPI) catalyzes the interconversion of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). This reaction is required for glycolysis and gluconeogenesis, and tpi has been predicted to be essential for growth of Mycobacterium tuberculosis. However, when studying a conditionally regulated tpi knockdown mutant, we noticed that depletion of TPI reduced growth of M. tuberculosis in media containing a single carbon source but not in media that contained both a glycolytic and a gluconeogenic carbon source. We used such two-carbon-source media to isolate a tpi deletion (Δtpi) mutant. The Δtpi mutant did not survive with single carbon substrates but grew like wild-type (WT) M. tuberculosis in the presence of both a glycolytic and a gluconeogenic carbon source. 13C metabolite tracing revealed the accumulation of TPI substrates in Δtpi and the absence of alternative triosephosphate isomerases and metabolic bypass reactions, which confirmed the requirement of TPI for glycolysis and gluconeogenesis in M. tuberculosis. The Δtpi strain was furthermore severely attenuated in the mouse model of tuberculosis, suggesting that M. tuberculosis cannot simultaneously access sufficient quantities of glycolytic and gluconeogenic carbon substrates to establish infection in mice.  
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 9 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 15 times in Scopus Article | Citations
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Created: Sat, 17 May 2014, 00:44:39 EST by Kylie Hengst on behalf of UQ Diamantina Institute