Programmed Delay of a Virulence Circuit Promotes <italic toggle="yes">Salmonella</italic> Pathogenicity

ABSTRACT Signal transduction systems dictate various cellular behaviors in response to environmental changes. To operate cellular programs appropriately, organisms have sophisticated regulatory factors to optimize the signal response. The PhoP/PhoQ master virulence regulatory system of the intracell...

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Autores principales:	Jeongjoon Choi, Heeju Kim, Yoonjee Chang, Woongjae Yoo, Dajeong Kim, Sangryeol Ryu
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	PhoP Salmonella ptsN virulence regulation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/0fc9fb1c4ca445c499f742103ae25679
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spelling	oai:doaj.org-article:0fc9fb1c4ca445c499f742103ae256792021-11-15T15:55:24ZProgrammed Delay of a Virulence Circuit Promotes <italic toggle="yes">Salmonella</italic> Pathogenicity10.1128/mBio.00291-192150-7511https://doaj.org/article/0fc9fb1c4ca445c499f742103ae256792019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00291-19https://doaj.org/toc/2150-7511ABSTRACT Signal transduction systems dictate various cellular behaviors in response to environmental changes. To operate cellular programs appropriately, organisms have sophisticated regulatory factors to optimize the signal response. The PhoP/PhoQ master virulence regulatory system of the intracellular pathogen Salmonella enterica is activated inside acidic macrophage phagosomes. Here we report that Salmonella delays the activation of this system inside macrophages using an inhibitory protein, EIIANtr (a component of the nitrogen-metabolic phosphotransferase system). We establish that EIIANtr directly restrains PhoP binding to its target promoter, thereby negatively controlling the expression of PhoP-activated genes. PhoP furthers its activation by promoting Lon-mediated degradation of EIIANtr at acidic pH. These results suggest that Salmonella ensures robust activation of its virulence system by suspending the activation of PhoP until a sufficient level of active PhoP is present to overcome the inhibitory effect of EIIANtr. Our findings reveal how a pathogen precisely and efficiently operates its virulence program during infection. IMPORTANCE To accomplish successful infection, pathogens must operate their virulence programs in a precise, time-sensitive, and coordinated manner. A major question is how pathogens control the timing of virulence gene expression during infection. Here we report that the intracellular pathogen Salmonella controls the timing and level of virulence gene expression by using an inhibitory protein, EIIANtr. A DNA binding master virulence regulator, PhoP, controls various virulence genes inside acidic phagosomes. Salmonella decreases EIIANtr amounts at acidic pH in a Lon- and PhoP-dependent manner. This, in turn, promotes expression of the PhoP-activated virulence program because EIIANtr hampers activation of PhoP-regulated genes by interfering with PhoP binding to DNA. EIIANtr enables Salmonella to impede the activation of PhoP-regulated gene expression inside macrophages. Our findings suggest that Salmonella achieves programmed delay of virulence gene activation by adjusting levels of an inhibitory factor.Jeongjoon ChoiHeeju KimYoonjee ChangWoongjae YooDajeong KimSangryeol RyuAmerican Society for MicrobiologyarticlePhoPSalmonellaptsNvirulence regulationMicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	PhoP Salmonella ptsN virulence regulation Microbiology QR1-502
spellingShingle	PhoP Salmonella ptsN virulence regulation Microbiology QR1-502 Jeongjoon Choi Heeju Kim Yoonjee Chang Woongjae Yoo Dajeong Kim Sangryeol Ryu Programmed Delay of a Virulence Circuit Promotes <italic toggle="yes">Salmonella</italic> Pathogenicity
description	ABSTRACT Signal transduction systems dictate various cellular behaviors in response to environmental changes. To operate cellular programs appropriately, organisms have sophisticated regulatory factors to optimize the signal response. The PhoP/PhoQ master virulence regulatory system of the intracellular pathogen Salmonella enterica is activated inside acidic macrophage phagosomes. Here we report that Salmonella delays the activation of this system inside macrophages using an inhibitory protein, EIIANtr (a component of the nitrogen-metabolic phosphotransferase system). We establish that EIIANtr directly restrains PhoP binding to its target promoter, thereby negatively controlling the expression of PhoP-activated genes. PhoP furthers its activation by promoting Lon-mediated degradation of EIIANtr at acidic pH. These results suggest that Salmonella ensures robust activation of its virulence system by suspending the activation of PhoP until a sufficient level of active PhoP is present to overcome the inhibitory effect of EIIANtr. Our findings reveal how a pathogen precisely and efficiently operates its virulence program during infection. IMPORTANCE To accomplish successful infection, pathogens must operate their virulence programs in a precise, time-sensitive, and coordinated manner. A major question is how pathogens control the timing of virulence gene expression during infection. Here we report that the intracellular pathogen Salmonella controls the timing and level of virulence gene expression by using an inhibitory protein, EIIANtr. A DNA binding master virulence regulator, PhoP, controls various virulence genes inside acidic phagosomes. Salmonella decreases EIIANtr amounts at acidic pH in a Lon- and PhoP-dependent manner. This, in turn, promotes expression of the PhoP-activated virulence program because EIIANtr hampers activation of PhoP-regulated genes by interfering with PhoP binding to DNA. EIIANtr enables Salmonella to impede the activation of PhoP-regulated gene expression inside macrophages. Our findings suggest that Salmonella achieves programmed delay of virulence gene activation by adjusting levels of an inhibitory factor.
format	article
author	Jeongjoon Choi Heeju Kim Yoonjee Chang Woongjae Yoo Dajeong Kim Sangryeol Ryu
author_facet	Jeongjoon Choi Heeju Kim Yoonjee Chang Woongjae Yoo Dajeong Kim Sangryeol Ryu
author_sort	Jeongjoon Choi
title	Programmed Delay of a Virulence Circuit Promotes <italic toggle="yes">Salmonella</italic> Pathogenicity
title_short	Programmed Delay of a Virulence Circuit Promotes <italic toggle="yes">Salmonella</italic> Pathogenicity
title_full	Programmed Delay of a Virulence Circuit Promotes <italic toggle="yes">Salmonella</italic> Pathogenicity
title_fullStr	Programmed Delay of a Virulence Circuit Promotes <italic toggle="yes">Salmonella</italic> Pathogenicity
title_full_unstemmed	Programmed Delay of a Virulence Circuit Promotes <italic toggle="yes">Salmonella</italic> Pathogenicity
title_sort	programmed delay of a virulence circuit promotes <italic toggle="yes">salmonella</italic> pathogenicity
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/0fc9fb1c4ca445c499f742103ae25679
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Programmed Delay of a Virulence Circuit Promotes <italic toggle="yes">Salmonella</italic> Pathogenicity

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