Regulation of proline metabolism in mycobacteria and its role in carbon metabolism under hypoxia

Michael Berney, Marion R. Weimar, Adam Heikal, Gregory M. Cook

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Genes with a role in proline metabolism are strongly expressed when mycobacterial cells are exposed to nutrient starvation and hypoxia. Here we show that proline metabolism in mycobacteria is mediated by the monofunctional enzymes Δ 1-pyrroline-5-carboxylate dehydrogenase (PruA) and proline dehydrogenase (PruB). Proline metabolism was controlled by a unique membrane-associated DNA-binding protein PruC. Under hypoxia, addition of proline led to higher biomass production than in the absence of proline despite excess carbon and nitrogen. To identify the mechanism responsible for this enhanced growth, microarray analysis of wild-type Mycobacterium smegmatis versus pruC mutant was performed. Expression of the DNA repair machinery and glyoxalases was increased in the pruC mutant. Glyoxalases are proposed to degrade methylglyoxal, a toxic metabolite produced by various bacteria due to an imbalance in intermediary metabolism, suggesting the pruC mutant was under methylglyoxal stress. Consistent with this notion, pruB and pruC mutants were hypersensitive to methylglyoxal Δ 1-pyrroline-5-carboxylate is reported to react with methylglyoxal to form non-toxic 2-acetyl-1-pyrroline, thus providing a link between proline metabolism and methylglyoxal detoxification. In support of this mechanism, we show that proline metabolism protects mycobacterial cells from methylglyoxal toxicity and that functional proline dehydrogenase, but not Δ 1-pyrroline-5-carboxylate dehydrogenase, is essential for this protective effect.

Original languageEnglish (US)
Pages (from-to)664-681
Number of pages18
JournalMolecular Microbiology
Volume84
Issue number4
DOIs
StatePublished - May 2012
Externally publishedYes

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Pyruvaldehyde
Mycobacterium
Proline
Carbon
1-Pyrroline-5-Carboxylate Dehydrogenase
Proline Oxidase
Mycobacterium smegmatis
Poisons
DNA-Binding Proteins
Microarray Analysis
Starvation
Hypoxia
DNA Repair
Biomass
Membrane Proteins
Nitrogen
Bacteria
Food
Enzymes
Growth

ASJC Scopus subject areas

  • Molecular Biology
  • Microbiology

Cite this

Regulation of proline metabolism in mycobacteria and its role in carbon metabolism under hypoxia. / Berney, Michael; Weimar, Marion R.; Heikal, Adam; Cook, Gregory M.

In: Molecular Microbiology, Vol. 84, No. 4, 05.2012, p. 664-681.

Research output: Contribution to journalArticle

Berney, Michael ; Weimar, Marion R. ; Heikal, Adam ; Cook, Gregory M. / Regulation of proline metabolism in mycobacteria and its role in carbon metabolism under hypoxia. In: Molecular Microbiology. 2012 ; Vol. 84, No. 4. pp. 664-681.
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