Zinc disrupts central carbon metabolism and capsule biosynthesis in Streptococcus pyogenes.

Ong, Cheryl-lynnY., Walker, Mark J. and McEwan, Alastair G. (2015) Zinc disrupts central carbon metabolism and capsule biosynthesis in Streptococcus pyogenes.. Scientific Reports, 5 Art No.: 10799: . doi:10.1038/srep10799.

Attached Files (Some files may be inaccessible until you login with your UQ eSpace credentials)
Name Description MIMEType Size Downloads
UQ362076_OA.pdf Open access application/pdf 1.08MB 0

Author Ong, Cheryl-lynnY.
Walker, Mark J.
McEwan, Alastair G.
Title Zinc disrupts central carbon metabolism and capsule biosynthesis in Streptococcus pyogenes.
Journal name Scientific Reports   Check publisher's open access policy
ISSN 2045-2322
Publication date 2015-06-01
Year available 2015
Sub-type Article (original research)
DOI 10.1038/srep10799.
Open Access Status DOI
Volume 5
Issue Art No.: 10799
Total pages 10
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 1000 General
Abstract Neutrophils release free zinc to eliminate the phagocytosed bacterial pathogen Streptococcus pyogenes (Group A Streptococcus; GAS). In this study, we investigated the mechanisms underpinning zinc toxicity towards this human pathogen, responsible for diseases ranging from pharyngitis and impetigo, to severe invasive infections. Using the globally-disseminated M1T1 GAS strain, we demonstrate that zinc stress impairs glucose metabolism through the inhibition of the glycolytic enzymes phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. In the presence of zinc, a metabolic shift to the tagatose-6-phosphate pathway allows conversion of D-galactose to dihydroxyacetone phosphate and glyceraldehyde phosphate, partially bypassing impaired glycolytic enzymes to generate pyruvate. Additionally, zinc inhibition of phosphoglucomutase results in decreased capsule biosynthesis. These data indicate that zinc exerts it toxicity via mechanisms that inhibit both GAS central carbon metabolism and virulence pathways.
Formatted abstract
Neutrophils release free zinc to eliminate the phagocytosed bacterial pathogen Streptococcus pyogenes (Group A Streptococcus; GAS). In this study, we investigated the mechanisms underpinning zinc toxicity towards this human pathogen, responsible for diseases ranging from pharyngitis and impetigo, to severe invasive infections. Using the globally-disseminated M1T1 GAS strain, we demonstrate that zinc stress impairs glucose metabolism through the inhibition of the glycolytic enzymes phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. In the presence of zinc, a metabolic shift to the tagatose-6-phosphate pathway allows conversion of D-galactose to dihydroxyacetone phosphate and glyceraldehyde phosphate, partially bypassing impaired glycolytic enzymes to generate pyruvate. Additionally, zinc inhibition of phosphoglucomutase results in decreased capsule biosynthesis. These data indicate that zinc exerts it toxicity via mechanisms that inhibit both GAS central carbon metabolism and virulence pathways.
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 1071659
1084460
565526
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Chemistry and Molecular Biosciences
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 20 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Fri, 05 Jun 2015, 19:53:02 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences