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J Biol Chem. 2016 May 27;291(22):11928-38. doi: 10.1074/jbc.M115.708149. Epub 2016 Apr 1.

Role of Glyoxylate Shunt in Oxidative Stress Response.

Author information

1
From the Laboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul 02841, Republic of Korea and.
2
the Department of Microbiology, Cornell University, Ithaca, New York 14853.
3
From the Laboratory of Molecular Environmental Microbiology, Department of Environmental Science and Ecological Engineering, Korea University, Seoul 02841, Republic of Korea and wpark@korea.ac.kr.

Abstract

The glyoxylate shunt (GS) is a two-step metabolic pathway (isocitrate lyase, aceA; and malate synthase, glcB) that serves as an alternative to the tricarboxylic acid cycle. The GS bypasses the carbon dioxide-producing steps of the tricarboxylic acid cycle and is essential for acetate and fatty acid metabolism in bacteria. GS can be up-regulated under conditions of oxidative stress, antibiotic stress, and host infection, which implies that it plays important but poorly explored roles in stress defense and pathogenesis. In many bacterial species, including Pseudomonas aeruginosa, aceA and glcB are not in an operon, unlike in Escherichia coli In P. aeruginosa, we explored relationships between GS genes and growth, transcription profiles, and biofilm formation. Contrary to our expectations, deletion of aceA in P. aeruginosa improved cell growth under conditions of oxidative and antibiotic stress. Transcriptome data suggested that aceA mutants underwent a metabolic shift toward aerobic denitrification; this was supported by additional evidence, including up-regulation of denitrification-related genes, decreased oxygen consumption without lowering ATP yield, increased production of denitrification intermediates (NO and N2O), and increased cyanide resistance. The aceA mutants also produced a thicker exopolysaccharide layer; that is, a phenotype consistent with aerobic denitrification. A bioinformatic survey across known bacterial genomes showed that only microorganisms capable of aerobic metabolism possess the glyoxylate shunt. This trend is consistent with the hypothesis that the GS plays a previously unrecognized role in allowing bacteria to tolerate oxidative stress.

KEYWORDS:

Pseudomonas aeruginosa (P. aeruginosa); bacteria; biofilm; denitification; glyoxylate bypass; isocitrate lyase; oxidative stress; tricarboxylic acid cycle (TCA cycle) (Krebs cycle)

PMID:
27036942
PMCID:
PMC4882458
DOI:
10.1074/jbc.M115.708149
[Indexed for MEDLINE]
Free PMC Article

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