Surface Export of GAPDH/SDH, a Glycolytic Enzyme, Is Essential for <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Virulence

ABSTRACT Streptococcal surface dehydrogenase (SDH) (glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) is an anchorless major multifunctional surface protein in group A Streptococcus (GAS) with the ability to bind important mammalian proteins, including plasmin(ogen). Although several biological prop...

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Autores principales:	Hong Jin, Shivangi Agarwal, Shivani Agarwal, Vijay Pancholi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/475bd77e75094422b3ec7a7b0060a654
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spelling	oai:doaj.org-article:475bd77e75094422b3ec7a7b0060a6542021-11-15T15:38:49ZSurface Export of GAPDH/SDH, a Glycolytic Enzyme, Is Essential for <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Virulence10.1128/mBio.00068-112150-7511https://doaj.org/article/475bd77e75094422b3ec7a7b0060a6542011-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00068-11https://doaj.org/toc/2150-7511ABSTRACT Streptococcal surface dehydrogenase (SDH) (glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) is an anchorless major multifunctional surface protein in group A Streptococcus (GAS) with the ability to bind important mammalian proteins, including plasmin(ogen). Although several biological properties of SDH are suggestive of its possible role in GAS virulence, its direct role in GAS pathogenesis has not been ascertained because it is essential for GAS survival. Thus, it has remained enigmatic as to “how and why” SDH/GAPDH is exported onto the bacterial surface. The present investigation highlights “why” SDH is exported onto the GAS surface. Differential microarray-based genome-wide transcript abundance analysis was carried out using a specific mutant, which was created by inserting a hydrophobic tail at the C-terminal end of SDH (M1-SDHHBtail) and thus preventing its exportation onto the GAS surface. This analysis revealed downregulation of the majority of genes involved in GAS virulence and genes belonging to carbohydrate and amino acid metabolism and upregulation of those related to lipid metabolism. The complete attenuation of this mutant for virulence in the mouse model and the decreased and increased virulence of the wild-type and mutant strains postcomplementation with SDHHBtail and SDH, respectively, indicated that the SDH surface export indeed regulates GAS virulence. M1-SDHHBtail also displayed unaltered growth patterns, increased intracellular ATP concentration and Hpr double phosphorylation, and significantly reduced pH tolerance, streptolysin S, and SpeB activities. These phenotypic and physiological changes observed in the mutant despite the unaltered expression levels of established transcriptional regulators further highlight the fact that SDH interfaces with many regulators and its surface exportation is essential for GAS virulence. IMPORTANCE Streptococcal surface dehydrogenase (SDH), a classical anchorless cytoplasmically localized glycolytic enzyme, is exported onto the group A Streptococcus (GAS) surface through a hitherto unknown mechanism(s). It has not been known why GAS or other prokaryotes should export this protein onto the surface. By genetic manipulations, we created a novel GAS mutant strain expressing SDH with a 12-amino-acid hydrophobic tail at its C-terminal end and thus were able to prevent its surface exportation without altering its enzymatic activity or growth pattern. Interestingly, the mutant was completely attenuated for virulence in a mouse peritonitis model. The global gene expression profiles of this mutant reveal that the surface exportation of SDH is mandatory to maintain GAS virulence. The ability of GAS as a successful pathogen to localize SDH in the cytoplasm as well as on the surface is physiologically relevant and dynamically obligatory to fine-tune the functions of many transcriptional regulators and also to exploit its virulence properties for infection.Hong JinShivangi AgarwalShivani AgarwalVijay PancholiAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 3 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Hong Jin Shivangi Agarwal Shivani Agarwal Vijay Pancholi Surface Export of GAPDH/SDH, a Glycolytic Enzyme, Is Essential for <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Virulence
description	ABSTRACT Streptococcal surface dehydrogenase (SDH) (glyceraldehyde-3-phosphate dehydrogenase [GAPDH]) is an anchorless major multifunctional surface protein in group A Streptococcus (GAS) with the ability to bind important mammalian proteins, including plasmin(ogen). Although several biological properties of SDH are suggestive of its possible role in GAS virulence, its direct role in GAS pathogenesis has not been ascertained because it is essential for GAS survival. Thus, it has remained enigmatic as to “how and why” SDH/GAPDH is exported onto the bacterial surface. The present investigation highlights “why” SDH is exported onto the GAS surface. Differential microarray-based genome-wide transcript abundance analysis was carried out using a specific mutant, which was created by inserting a hydrophobic tail at the C-terminal end of SDH (M1-SDHHBtail) and thus preventing its exportation onto the GAS surface. This analysis revealed downregulation of the majority of genes involved in GAS virulence and genes belonging to carbohydrate and amino acid metabolism and upregulation of those related to lipid metabolism. The complete attenuation of this mutant for virulence in the mouse model and the decreased and increased virulence of the wild-type and mutant strains postcomplementation with SDHHBtail and SDH, respectively, indicated that the SDH surface export indeed regulates GAS virulence. M1-SDHHBtail also displayed unaltered growth patterns, increased intracellular ATP concentration and Hpr double phosphorylation, and significantly reduced pH tolerance, streptolysin S, and SpeB activities. These phenotypic and physiological changes observed in the mutant despite the unaltered expression levels of established transcriptional regulators further highlight the fact that SDH interfaces with many regulators and its surface exportation is essential for GAS virulence. IMPORTANCE Streptococcal surface dehydrogenase (SDH), a classical anchorless cytoplasmically localized glycolytic enzyme, is exported onto the group A Streptococcus (GAS) surface through a hitherto unknown mechanism(s). It has not been known why GAS or other prokaryotes should export this protein onto the surface. By genetic manipulations, we created a novel GAS mutant strain expressing SDH with a 12-amino-acid hydrophobic tail at its C-terminal end and thus were able to prevent its surface exportation without altering its enzymatic activity or growth pattern. Interestingly, the mutant was completely attenuated for virulence in a mouse peritonitis model. The global gene expression profiles of this mutant reveal that the surface exportation of SDH is mandatory to maintain GAS virulence. The ability of GAS as a successful pathogen to localize SDH in the cytoplasm as well as on the surface is physiologically relevant and dynamically obligatory to fine-tune the functions of many transcriptional regulators and also to exploit its virulence properties for infection.
format	article
author	Hong Jin Shivangi Agarwal Shivani Agarwal Vijay Pancholi
author_facet	Hong Jin Shivangi Agarwal Shivani Agarwal Vijay Pancholi
author_sort	Hong Jin
title	Surface Export of GAPDH/SDH, a Glycolytic Enzyme, Is Essential for <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Virulence
title_short	Surface Export of GAPDH/SDH, a Glycolytic Enzyme, Is Essential for <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Virulence
title_full	Surface Export of GAPDH/SDH, a Glycolytic Enzyme, Is Essential for <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Virulence
title_fullStr	Surface Export of GAPDH/SDH, a Glycolytic Enzyme, Is Essential for <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Virulence
title_full_unstemmed	Surface Export of GAPDH/SDH, a Glycolytic Enzyme, Is Essential for <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Virulence
title_sort	surface export of gapdh/sdh, a glycolytic enzyme, is essential for <named-content content-type="genus-species">streptococcus pyogenes</named-content> virulence
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/475bd77e75094422b3ec7a7b0060a654
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Surface Export of GAPDH/SDH, a Glycolytic Enzyme, Is Essential for <named-content content-type="genus-species">Streptococcus pyogenes</named-content> Virulence

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