The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in <named-content content-type="genus-species">Yersinia pestis</named-content> during Planktonic Growth and Growth in Biofilms

ABSTRACT Cyclic AMP (cAMP) receptor protein (Crp) is an important transcriptional regulator of Yersinia pestis. Expression of crp increases during pneumonic plague as the pathogen depletes glucose and forms large biofilms within lungs. To better understand control of Y. pestis Crp, we determined a 1...

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Autores principales:	Jeremy T. Ritzert, George Minasov, Ryan Embry, Matthew J. Schipma, Karla J. F. Satchell
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Yersinia pestis plague Crp RNA-seq structure quorum sensing Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e8737ece1f6c4b319c76b873c0545702
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spelling	oai:doaj.org-article:e8737ece1f6c4b319c76b873c05457022021-11-15T15:54:47ZThe Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in <named-content content-type="genus-species">Yersinia pestis</named-content> during Planktonic Growth and Growth in Biofilms10.1128/mBio.02613-192150-7511https://doaj.org/article/e8737ece1f6c4b319c76b873c05457022019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02613-19https://doaj.org/toc/2150-7511ABSTRACT Cyclic AMP (cAMP) receptor protein (Crp) is an important transcriptional regulator of Yersinia pestis. Expression of crp increases during pneumonic plague as the pathogen depletes glucose and forms large biofilms within lungs. To better understand control of Y. pestis Crp, we determined a 1.8-Å crystal structure of the protein-cAMP complex. We found that compared to Escherichia coli Crp, C helix amino acid substitutions in Y. pestis Crp did not impact the cAMP dependency of Crp to bind DNA promoters. To investigate Y. pestis Crp-regulated genes during plague pneumonia, we performed RNA sequencing on both wild-type and Δcrp mutant bacteria growing in planktonic and biofilm states in minimal media with glucose or glycerol. Y. pestis Crp was found to dramatically alter expression of hundreds of genes in a manner dependent upon carbon source and growth state. Gel shift assays confirmed direct regulation of the malT and ptsG promoters, and Crp was then linked to Y. pestis growth on maltose as a sole carbon source. Iron regulation genes ybtA and fyuA were found to be indirectly regulated by Crp. A new connection between carbon source and quorum sensing was revealed as Crp was found to regulate production of acyl-homoserine lactones (AHLs) through direct and indirect regulation of genes for AHL synthetases and receptors. AHLs were subsequently identified in the lungs of Y. pestis-infected mice when crp expression was highest in Y. pestis biofilms. Thus, in addition to the well-studied pla gene, other Crp-regulated genes likely have important functions during plague infection. IMPORTANCE Bacterial pathogens have evolved extensive signaling pathways to translate environmental signals into changes in gene expression. While Crp has long been appreciated for its role in regulating metabolism of carbon sources in many bacterial species, transcriptional profiling has revealed that this protein regulates many other aspects of bacterial physiology. The plague pathogen Y. pestis requires this global regulator to survive in blood, skin, and lungs. During disease progression, this organism adapts to changes within these niches. In addition to regulating genes for metabolism of nonglucose sugars, we found that Crp regulates genes for virulence, metal acquisition, and quorum sensing by direct or indirect mechanisms. Thus, this single transcriptional regulator, which responds to changes in available carbon sources, can regulate multiple critical behaviors for causing disease.Jeremy T. RitzertGeorge MinasovRyan EmbryMatthew J. SchipmaKarla J. F. SatchellAmerican Society for MicrobiologyarticleYersinia pestisplagueCrpRNA-seqstructurequorum sensingMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Yersinia pestis plague Crp RNA-seq structure quorum sensing Microbiology QR1-502
spellingShingle	Yersinia pestis plague Crp RNA-seq structure quorum sensing Microbiology QR1-502 Jeremy T. Ritzert George Minasov Ryan Embry Matthew J. Schipma Karla J. F. Satchell The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in <named-content content-type="genus-species">Yersinia pestis</named-content> during Planktonic Growth and Growth in Biofilms
description	ABSTRACT Cyclic AMP (cAMP) receptor protein (Crp) is an important transcriptional regulator of Yersinia pestis. Expression of crp increases during pneumonic plague as the pathogen depletes glucose and forms large biofilms within lungs. To better understand control of Y. pestis Crp, we determined a 1.8-Å crystal structure of the protein-cAMP complex. We found that compared to Escherichia coli Crp, C helix amino acid substitutions in Y. pestis Crp did not impact the cAMP dependency of Crp to bind DNA promoters. To investigate Y. pestis Crp-regulated genes during plague pneumonia, we performed RNA sequencing on both wild-type and Δcrp mutant bacteria growing in planktonic and biofilm states in minimal media with glucose or glycerol. Y. pestis Crp was found to dramatically alter expression of hundreds of genes in a manner dependent upon carbon source and growth state. Gel shift assays confirmed direct regulation of the malT and ptsG promoters, and Crp was then linked to Y. pestis growth on maltose as a sole carbon source. Iron regulation genes ybtA and fyuA were found to be indirectly regulated by Crp. A new connection between carbon source and quorum sensing was revealed as Crp was found to regulate production of acyl-homoserine lactones (AHLs) through direct and indirect regulation of genes for AHL synthetases and receptors. AHLs were subsequently identified in the lungs of Y. pestis-infected mice when crp expression was highest in Y. pestis biofilms. Thus, in addition to the well-studied pla gene, other Crp-regulated genes likely have important functions during plague infection. IMPORTANCE Bacterial pathogens have evolved extensive signaling pathways to translate environmental signals into changes in gene expression. While Crp has long been appreciated for its role in regulating metabolism of carbon sources in many bacterial species, transcriptional profiling has revealed that this protein regulates many other aspects of bacterial physiology. The plague pathogen Y. pestis requires this global regulator to survive in blood, skin, and lungs. During disease progression, this organism adapts to changes within these niches. In addition to regulating genes for metabolism of nonglucose sugars, we found that Crp regulates genes for virulence, metal acquisition, and quorum sensing by direct or indirect mechanisms. Thus, this single transcriptional regulator, which responds to changes in available carbon sources, can regulate multiple critical behaviors for causing disease.
format	article
author	Jeremy T. Ritzert George Minasov Ryan Embry Matthew J. Schipma Karla J. F. Satchell
author_facet	Jeremy T. Ritzert George Minasov Ryan Embry Matthew J. Schipma Karla J. F. Satchell
author_sort	Jeremy T. Ritzert
title	The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in <named-content content-type="genus-species">Yersinia pestis</named-content> during Planktonic Growth and Growth in Biofilms
title_short	The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in <named-content content-type="genus-species">Yersinia pestis</named-content> during Planktonic Growth and Growth in Biofilms
title_full	The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in <named-content content-type="genus-species">Yersinia pestis</named-content> during Planktonic Growth and Growth in Biofilms
title_fullStr	The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in <named-content content-type="genus-species">Yersinia pestis</named-content> during Planktonic Growth and Growth in Biofilms
title_full_unstemmed	The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in <named-content content-type="genus-species">Yersinia pestis</named-content> during Planktonic Growth and Growth in Biofilms
title_sort	cyclic amp receptor protein regulates quorum sensing and global gene expression in <named-content content-type="genus-species">yersinia pestis</named-content> during planktonic growth and growth in biofilms
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/e8737ece1f6c4b319c76b873c0545702
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The Cyclic AMP Receptor Protein Regulates Quorum Sensing and Global Gene Expression in <named-content content-type="genus-species">Yersinia pestis</named-content> during Planktonic Growth and Growth in Biofilms

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