Defence against methylglyoxal in Group A Streptococcus: a role for Glyoxylase I in bacterial virulence and survival in neutrophils?

Zhang, May M., Ong, Cheryl-lynn, Walker, Mark J. and McEwan, Alastair G. (2015) Defence against methylglyoxal in Group A Streptococcus: a role for Glyoxylase I in bacterial virulence and survival in neutrophils?. Pathogens and Disease, 74 2: . doi:10.1093/femspd/ftv122


Author Zhang, May M.
Ong, Cheryl-lynn
Walker, Mark J.
McEwan, Alastair G.
Title Defence against methylglyoxal in Group A Streptococcus: a role for Glyoxylase I in bacterial virulence and survival in neutrophils?
Journal name Pathogens and Disease   Check publisher's open access policy
ISSN 2049-632X
Publication date 2015-12-23
Year available 2015
Sub-type Article (original research)
DOI 10.1093/femspd/ftv122
Open Access Status Not yet assessed
Volume 74
Issue 2
Total pages 8
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Methylglyoxal is a dicarbonyl compound that acts as a toxic electrophile in biological systems. Methylglyoxal is produced in certain bacteria as a byproduct of glycolysis through methylglyoxal synthase. Like many bacteria, Group A Streptococcus (GAS), a Gram-positive human pathogen responsible for a wide spectrum of diseases, uses a two-step glyoxalase system to remove methylglyoxal. However, bioinformatic analysis revealed that no homologue of methylglyoxal synthase is present in GAS, suggesting that the role of the glyoxalase system is to detoxify methylglyoxal produced by the host. In this study, we investigated the role of methylglyoxal detoxification in the pathogenesis of GAS. A mutant (5448ΔgloA), deficient in glyoxylase I (S-lactoylglutathione lyase), was constructed and tested for susceptibility to methylglyoxal, human neutrophil survival and virulence in a murine model of infection. 5448ΔgloA was more sensitive to methylglyoxal and was also more susceptible to human neutrophil killing. Inhibition of neutrophil myeloperoxidase rescued the gloA-deficient mutant indicating that this enzyme was required for methylglyoxal production. Furthermore, the 5448ΔgloA mutant was slower at disseminating into the blood in the murine model. These data suggest that neutrophils produce methylglyoxal as an antimicrobial agent during bacterial infection, and the glyoxalase system is part of the GAS defence against the innate immune system during pathogenesis.
Keyword GloA
Methylglyoxal
Glyoxalase system
Aldehyde stress response
Group A Streptococcus
Streptococcus pyogenes
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
 
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