<italic toggle="yes">Staphylococcus aureus</italic> Responds to the Central Metabolite Pyruvate To Regulate Virulence

ABSTRACT Staphylococcus aureus is a versatile bacterial pathogen that can cause significant disease burden and mortality. Like other pathogens, S. aureus must adapt to its environment to produce virulence factors to survive the immune responses evoked by infection. Despite the importance of environm...

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Autores principales:	Lamia Harper, Divya Balasubramanian, Elizabeth A. Ohneck, William E. Sause, Jessica Chapman, Bryan Mejia-Sosa, Tenzin Lhakhang, Adriana Heguy, Aristotelis Tsirigos, Beatrix Ueberheide, Jeffrey M. Boyd, Desmond S. Lun, Victor J. Torres
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Staphylococcus aureus gene regulation infection metabolite pathogenesis pyruvate Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/886e6fd740334048b685bd4b0f4aa6f0
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spelling	oai:doaj.org-article:886e6fd740334048b685bd4b0f4aa6f02021-11-15T15:53:26Z<italic toggle="yes">Staphylococcus aureus</italic> Responds to the Central Metabolite Pyruvate To Regulate Virulence10.1128/mBio.02272-172150-7511https://doaj.org/article/886e6fd740334048b685bd4b0f4aa6f02018-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02272-17https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus aureus is a versatile bacterial pathogen that can cause significant disease burden and mortality. Like other pathogens, S. aureus must adapt to its environment to produce virulence factors to survive the immune responses evoked by infection. Despite the importance of environmental signals for S. aureus pathogenicity, only a limited number of these signals have been investigated in detail for their ability to modulate virulence. Here we show that pyruvate, a central metabolite, causes alterations in the overall metabolic flux of S. aureus and enhances its pathogenicity. We demonstrate that pyruvate induces the production of virulence factors such as the pore-forming leucocidins and that this induction results in increased virulence of community-acquired methicillin-resistant S. aureus (CA-MRSA) clone USA300. Specifically, we show that an efficient “pyruvate response” requires the activation of S. aureus master regulators AgrAC and SaeRS as well as the ArlRS two-component system. Altogether, our report further establishes a strong relationship between metabolism and virulence and identifies pyruvate as a novel regulatory signal for the coordination of the S. aureus virulon through intricate regulatory networks. IMPORTANCE Delineation of the influence of host-derived small molecules on the makeup of human pathogens is a growing field in understanding host-pathogen interactions. S. aureus is a prominent pathogen that colonizes up to one-third of the human population and can cause serious infections that result in mortality in ~15% of cases. Here, we show that pyruvate, a key nutrient and central metabolite, causes global changes to the metabolic flux of S. aureus and activates regulatory networks that allow significant increases in the production of leucocidins. These and other virulence factors are critical for S. aureus to infect diverse host niches, initiate infections, and effectively subvert host immune responses. Understanding how environmental signals, particularly ones that are essential to and prominent in the human host, affect virulence will allow us to better understand pathogenicity and consider more-targeted approaches to tackling the current S. aureus epidemic.Lamia HarperDivya BalasubramanianElizabeth A. OhneckWilliam E. SauseJessica ChapmanBryan Mejia-SosaTenzin LhakhangAdriana HeguyAristotelis TsirigosBeatrix UeberheideJeffrey M. BoydDesmond S. LunVictor J. TorresAmerican Society for MicrobiologyarticleStaphylococcus aureusgene regulationinfectionmetabolitepathogenesispyruvateMicrobiologyQR1-502ENmBio, Vol 9, Iss 1 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus aureus gene regulation infection metabolite pathogenesis pyruvate Microbiology QR1-502
spellingShingle	Staphylococcus aureus gene regulation infection metabolite pathogenesis pyruvate Microbiology QR1-502 Lamia Harper Divya Balasubramanian Elizabeth A. Ohneck William E. Sause Jessica Chapman Bryan Mejia-Sosa Tenzin Lhakhang Adriana Heguy Aristotelis Tsirigos Beatrix Ueberheide Jeffrey M. Boyd Desmond S. Lun Victor J. Torres <italic toggle="yes">Staphylococcus aureus</italic> Responds to the Central Metabolite Pyruvate To Regulate Virulence
description	ABSTRACT Staphylococcus aureus is a versatile bacterial pathogen that can cause significant disease burden and mortality. Like other pathogens, S. aureus must adapt to its environment to produce virulence factors to survive the immune responses evoked by infection. Despite the importance of environmental signals for S. aureus pathogenicity, only a limited number of these signals have been investigated in detail for their ability to modulate virulence. Here we show that pyruvate, a central metabolite, causes alterations in the overall metabolic flux of S. aureus and enhances its pathogenicity. We demonstrate that pyruvate induces the production of virulence factors such as the pore-forming leucocidins and that this induction results in increased virulence of community-acquired methicillin-resistant S. aureus (CA-MRSA) clone USA300. Specifically, we show that an efficient “pyruvate response” requires the activation of S. aureus master regulators AgrAC and SaeRS as well as the ArlRS two-component system. Altogether, our report further establishes a strong relationship between metabolism and virulence and identifies pyruvate as a novel regulatory signal for the coordination of the S. aureus virulon through intricate regulatory networks. IMPORTANCE Delineation of the influence of host-derived small molecules on the makeup of human pathogens is a growing field in understanding host-pathogen interactions. S. aureus is a prominent pathogen that colonizes up to one-third of the human population and can cause serious infections that result in mortality in ~15% of cases. Here, we show that pyruvate, a key nutrient and central metabolite, causes global changes to the metabolic flux of S. aureus and activates regulatory networks that allow significant increases in the production of leucocidins. These and other virulence factors are critical for S. aureus to infect diverse host niches, initiate infections, and effectively subvert host immune responses. Understanding how environmental signals, particularly ones that are essential to and prominent in the human host, affect virulence will allow us to better understand pathogenicity and consider more-targeted approaches to tackling the current S. aureus epidemic.
format	article
author	Lamia Harper Divya Balasubramanian Elizabeth A. Ohneck William E. Sause Jessica Chapman Bryan Mejia-Sosa Tenzin Lhakhang Adriana Heguy Aristotelis Tsirigos Beatrix Ueberheide Jeffrey M. Boyd Desmond S. Lun Victor J. Torres
author_facet	Lamia Harper Divya Balasubramanian Elizabeth A. Ohneck William E. Sause Jessica Chapman Bryan Mejia-Sosa Tenzin Lhakhang Adriana Heguy Aristotelis Tsirigos Beatrix Ueberheide Jeffrey M. Boyd Desmond S. Lun Victor J. Torres
author_sort	Lamia Harper
title	<italic toggle="yes">Staphylococcus aureus</italic> Responds to the Central Metabolite Pyruvate To Regulate Virulence
title_short	<italic toggle="yes">Staphylococcus aureus</italic> Responds to the Central Metabolite Pyruvate To Regulate Virulence
title_full	<italic toggle="yes">Staphylococcus aureus</italic> Responds to the Central Metabolite Pyruvate To Regulate Virulence
title_fullStr	<italic toggle="yes">Staphylococcus aureus</italic> Responds to the Central Metabolite Pyruvate To Regulate Virulence
title_full_unstemmed	<italic toggle="yes">Staphylococcus aureus</italic> Responds to the Central Metabolite Pyruvate To Regulate Virulence
title_sort	<italic toggle="yes">staphylococcus aureus</italic> responds to the central metabolite pyruvate to regulate virulence
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/886e6fd740334048b685bd4b0f4aa6f0
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<italic toggle="yes">Staphylococcus aureus</italic> Responds to the Central Metabolite Pyruvate To Regulate Virulence

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