A Dopamine-Responsive Signal Transduction Controls Transcription of <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium Virulence Genes

ABSTRACT We have shown that the ligand-responsive MarR family member SlyA plays an important role in transcription activation of multiple virulence genes in Salmonella enterica serovar Typhimurium by responding to guanosine tetraphosphate (ppGpp). Here, we demonstrate that another MarR family member...

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Autores principales:	Dezhi Yang, Ying Kong, Wei Sun, Wei Kong, Yixin Shi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	bacterial signal transduction catecholamine neurotransmitter dopamine MarR family virulence regulator EmrR PhoP/PhoQ and SlyA feedforward loop Salmonella pathogenicity island 2 (SPI-2) Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/9301ad17c75a413e8f1d950d49fa6d12
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spelling	oai:doaj.org-article:9301ad17c75a413e8f1d950d49fa6d122021-11-15T15:55:25ZA Dopamine-Responsive Signal Transduction Controls Transcription of <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium Virulence Genes10.1128/mBio.02772-182150-7511https://doaj.org/article/9301ad17c75a413e8f1d950d49fa6d122019-04-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02772-18https://doaj.org/toc/2150-7511ABSTRACT We have shown that the ligand-responsive MarR family member SlyA plays an important role in transcription activation of multiple virulence genes in Salmonella enterica serovar Typhimurium by responding to guanosine tetraphosphate (ppGpp). Here, we demonstrate that another MarR family member, EmrR, is required for virulence of S. Typhimurium and another enteric bacterium, Yersinia pestis. EmrR is found to activate transcription of an array of virulence determinants, including Salmonella pathogenicity island 2 (SPI-2) genes and several divergent operons, which have been shown to be activated by SlyA and the PhoP/PhoQ two-component system. We studied the regulatory effect of EmrR on one of these genetic loci, i.e., the pagC-pagD divergent operon, and characterized a catecholamine neurotransmitter, dopamine, as an EmrR-sensed signal. Dopamine acts on EmrR to reduce its ability to bind to the target promoters, thus functioning as a negative signal to downregulate this EmrR-activated transcription. EmrR can bind to AT-rich sequences, which particularly overlap the SlyA and PhoP binding sites in the pagC-pagD divergent promoter. EmrR is a priming transcription regulator that binds its target promoters prior to successive transcription activators, by which it displaces universal silencer H-NS from these promoters and facilitates successive regulators to bind these regions. Regulation of the Salmonella-specific gene in Escherichia coli and Y. pestis reveals that EmrR-dependent regulation is conserved in enteric bacteria. These observations suggest that EmrR is a transcription activator to control the expression of virulence genes, including the SPI-2 genes. Dopamine can act on the EmrR-mediated signal transduction, thus downregulating expression of these virulence factors. IMPORTANCE In this study, MarR family regulator EmrR is identified as a novel virulence factor of enteric bacteria, here exemplified by Salmonella enterica serovar Typhimurium and Yersinia pestis. EmrR exerts an essential effect as a transcription activator for expression of virulence determinants, including Salmonella pathogenicity island 2 genes and a set of horizontally acquired genetic loci that formed divergent operons. EmrR senses the neurotransmitter dopamine and is subsequently released from target promoters, resulting in downregulation of the virulence gene expression. Through this action on EmrR, dopamine can weaken Salmonella resistance against host defense mechanisms. This provides an explanation for the previous observation that dopamine inhibits bacterial infection in animal gastrointestinal tracts. Our findings provide evidence that this neurotransmitter can modulate bacterial gene expression through interaction with virulence regulator EmrR.Dezhi YangYing KongWei SunWei KongYixin ShiAmerican Society for Microbiologyarticlebacterial signal transductioncatecholamine neurotransmitter dopamineMarR family virulence regulator EmrRPhoP/PhoQ and SlyA feedforward loopSalmonella pathogenicity island 2 (SPI-2)MicrobiologyQR1-502ENmBio, Vol 10, Iss 2 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	bacterial signal transduction catecholamine neurotransmitter dopamine MarR family virulence regulator EmrR PhoP/PhoQ and SlyA feedforward loop Salmonella pathogenicity island 2 (SPI-2) Microbiology QR1-502
spellingShingle	bacterial signal transduction catecholamine neurotransmitter dopamine MarR family virulence regulator EmrR PhoP/PhoQ and SlyA feedforward loop Salmonella pathogenicity island 2 (SPI-2) Microbiology QR1-502 Dezhi Yang Ying Kong Wei Sun Wei Kong Yixin Shi A Dopamine-Responsive Signal Transduction Controls Transcription of <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium Virulence Genes
description	ABSTRACT We have shown that the ligand-responsive MarR family member SlyA plays an important role in transcription activation of multiple virulence genes in Salmonella enterica serovar Typhimurium by responding to guanosine tetraphosphate (ppGpp). Here, we demonstrate that another MarR family member, EmrR, is required for virulence of S. Typhimurium and another enteric bacterium, Yersinia pestis. EmrR is found to activate transcription of an array of virulence determinants, including Salmonella pathogenicity island 2 (SPI-2) genes and several divergent operons, which have been shown to be activated by SlyA and the PhoP/PhoQ two-component system. We studied the regulatory effect of EmrR on one of these genetic loci, i.e., the pagC-pagD divergent operon, and characterized a catecholamine neurotransmitter, dopamine, as an EmrR-sensed signal. Dopamine acts on EmrR to reduce its ability to bind to the target promoters, thus functioning as a negative signal to downregulate this EmrR-activated transcription. EmrR can bind to AT-rich sequences, which particularly overlap the SlyA and PhoP binding sites in the pagC-pagD divergent promoter. EmrR is a priming transcription regulator that binds its target promoters prior to successive transcription activators, by which it displaces universal silencer H-NS from these promoters and facilitates successive regulators to bind these regions. Regulation of the Salmonella-specific gene in Escherichia coli and Y. pestis reveals that EmrR-dependent regulation is conserved in enteric bacteria. These observations suggest that EmrR is a transcription activator to control the expression of virulence genes, including the SPI-2 genes. Dopamine can act on the EmrR-mediated signal transduction, thus downregulating expression of these virulence factors. IMPORTANCE In this study, MarR family regulator EmrR is identified as a novel virulence factor of enteric bacteria, here exemplified by Salmonella enterica serovar Typhimurium and Yersinia pestis. EmrR exerts an essential effect as a transcription activator for expression of virulence determinants, including Salmonella pathogenicity island 2 genes and a set of horizontally acquired genetic loci that formed divergent operons. EmrR senses the neurotransmitter dopamine and is subsequently released from target promoters, resulting in downregulation of the virulence gene expression. Through this action on EmrR, dopamine can weaken Salmonella resistance against host defense mechanisms. This provides an explanation for the previous observation that dopamine inhibits bacterial infection in animal gastrointestinal tracts. Our findings provide evidence that this neurotransmitter can modulate bacterial gene expression through interaction with virulence regulator EmrR.
format	article
author	Dezhi Yang Ying Kong Wei Sun Wei Kong Yixin Shi
author_facet	Dezhi Yang Ying Kong Wei Sun Wei Kong Yixin Shi
author_sort	Dezhi Yang
title	A Dopamine-Responsive Signal Transduction Controls Transcription of <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium Virulence Genes
title_short	A Dopamine-Responsive Signal Transduction Controls Transcription of <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium Virulence Genes
title_full	A Dopamine-Responsive Signal Transduction Controls Transcription of <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium Virulence Genes
title_fullStr	A Dopamine-Responsive Signal Transduction Controls Transcription of <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium Virulence Genes
title_full_unstemmed	A Dopamine-Responsive Signal Transduction Controls Transcription of <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium Virulence Genes
title_sort	dopamine-responsive signal transduction controls transcription of <named-content content-type="genus-species">salmonella enterica</named-content> serovar typhimurium virulence genes
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/9301ad17c75a413e8f1d950d49fa6d12
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A Dopamine-Responsive Signal Transduction Controls Transcription of <named-content content-type="genus-species">Salmonella enterica</named-content> Serovar Typhimurium Virulence Genes

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