Identification of a Novel LysR-Type Transcriptional Regulator in <named-content content-type="genus-species">Staphylococcus aureus</named-content> That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection

ABSTRACT Staphylococcus aureus is a common cause of bacteremia that can lead to severe complications once the bacteria exit the bloodstream and establish infection in secondary organs. Despite its clinical relevance, little is known about the bacterial factors facilitating the development of these m...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Michaela Groma, Sarah A. Horst, Sudip Das, Bruno Huettel, Maximilian Klepsch, Thomas Rudel, Eva Medina, Martin Fraunholz
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Staphylococcus aureus metabolic adaptation secondary site infection transcriptional regulation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/673e4dced8ba42758f9c0c1595d7dd52
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:673e4dced8ba42758f9c0c1595d7dd52
record_format	dspace
spelling	oai:doaj.org-article:673e4dced8ba42758f9c0c1595d7dd522021-11-15T15:56:43ZIdentification of a Novel LysR-Type Transcriptional Regulator in <named-content content-type="genus-species">Staphylococcus aureus</named-content> That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection10.1128/mBio.01646-202150-7511https://doaj.org/article/673e4dced8ba42758f9c0c1595d7dd522020-08-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01646-20https://doaj.org/toc/2150-7511ABSTRACT Staphylococcus aureus is a common cause of bacteremia that can lead to severe complications once the bacteria exit the bloodstream and establish infection in secondary organs. Despite its clinical relevance, little is known about the bacterial factors facilitating the development of these metastatic infections. Here, we used an S. aureus transposon mutant library coupled to transposon insertion sequencing (Tn-Seq) to identify genes that are critical for efficient bacterial colonization of secondary organs in a murine model of metastatic bloodstream infection. Our transposon screen identified a LysR-type transcriptional regulator (LTTR), which was required for efficient colonization of secondary organs such as the kidneys in infected mice. The critical role of LTTR in secondary organ colonization was confirmed using an isogenic mutant deficient in the expression of LTTR. To identify the set of genes controlled by LTTR, we used an S. aureus strain carrying the LTTR gene in an inducible expression plasmid. Gene expression analysis upon induction of LTTR showed increased transcription of genes involved in branched-chain amino acid biosynthesis, a methionine sulfoxide reductase, and a copper transporter as well as decreased transcription of genes coding for urease and components of pyrimidine nucleotides. Furthermore, we show that transcription of LTTR is repressed by glucose, is induced under microaerobic conditions, and required trace amounts of copper ions. Our data thus pinpoints LTTR as an important element that enables a rapid adaptation of S. aureus to the changing host microenvironment. IMPORTANCE Staphylococcus aureus is an important pathogen that can disseminate via the bloodstream and establish metastatic infections in distant organs. To achieve a better understanding of the bacterial factors facilitating the development of these metastatic infections, we used in this study a Staphylococcus aureus transposon mutant library in a murine model of intravenous infection, where bacteria first colonize the liver as the primary infection site and subsequently progress to secondary sites such as the kidney and bones. We identified a novel LysR-type transcriptional regulator (LTTR), which was specifically required by S. aureus for efficient colonization of secondary organs. We also determined the transcriptional activation as well as the regulon of LTTR, which suggests that this regulator is involved in the metabolic adaptation of S. aureus to the host microenvironment found in secondary infection sites.Michaela GromaSarah A. HorstSudip DasBruno HuettelMaximilian KlepschThomas RudelEva MedinaMartin FraunholzAmerican Society for MicrobiologyarticleStaphylococcus aureusmetabolic adaptationsecondary site infectiontranscriptional regulationMicrobiologyQR1-502ENmBio, Vol 11, Iss 4 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Staphylococcus aureus metabolic adaptation secondary site infection transcriptional regulation Microbiology QR1-502
spellingShingle	Staphylococcus aureus metabolic adaptation secondary site infection transcriptional regulation Microbiology QR1-502 Michaela Groma Sarah A. Horst Sudip Das Bruno Huettel Maximilian Klepsch Thomas Rudel Eva Medina Martin Fraunholz Identification of a Novel LysR-Type Transcriptional Regulator in <named-content content-type="genus-species">Staphylococcus aureus</named-content> That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection
description	ABSTRACT Staphylococcus aureus is a common cause of bacteremia that can lead to severe complications once the bacteria exit the bloodstream and establish infection in secondary organs. Despite its clinical relevance, little is known about the bacterial factors facilitating the development of these metastatic infections. Here, we used an S. aureus transposon mutant library coupled to transposon insertion sequencing (Tn-Seq) to identify genes that are critical for efficient bacterial colonization of secondary organs in a murine model of metastatic bloodstream infection. Our transposon screen identified a LysR-type transcriptional regulator (LTTR), which was required for efficient colonization of secondary organs such as the kidneys in infected mice. The critical role of LTTR in secondary organ colonization was confirmed using an isogenic mutant deficient in the expression of LTTR. To identify the set of genes controlled by LTTR, we used an S. aureus strain carrying the LTTR gene in an inducible expression plasmid. Gene expression analysis upon induction of LTTR showed increased transcription of genes involved in branched-chain amino acid biosynthesis, a methionine sulfoxide reductase, and a copper transporter as well as decreased transcription of genes coding for urease and components of pyrimidine nucleotides. Furthermore, we show that transcription of LTTR is repressed by glucose, is induced under microaerobic conditions, and required trace amounts of copper ions. Our data thus pinpoints LTTR as an important element that enables a rapid adaptation of S. aureus to the changing host microenvironment. IMPORTANCE Staphylococcus aureus is an important pathogen that can disseminate via the bloodstream and establish metastatic infections in distant organs. To achieve a better understanding of the bacterial factors facilitating the development of these metastatic infections, we used in this study a Staphylococcus aureus transposon mutant library in a murine model of intravenous infection, where bacteria first colonize the liver as the primary infection site and subsequently progress to secondary sites such as the kidney and bones. We identified a novel LysR-type transcriptional regulator (LTTR), which was specifically required by S. aureus for efficient colonization of secondary organs. We also determined the transcriptional activation as well as the regulon of LTTR, which suggests that this regulator is involved in the metabolic adaptation of S. aureus to the host microenvironment found in secondary infection sites.
format	article
author	Michaela Groma Sarah A. Horst Sudip Das Bruno Huettel Maximilian Klepsch Thomas Rudel Eva Medina Martin Fraunholz
author_facet	Michaela Groma Sarah A. Horst Sudip Das Bruno Huettel Maximilian Klepsch Thomas Rudel Eva Medina Martin Fraunholz
author_sort	Michaela Groma
title	Identification of a Novel LysR-Type Transcriptional Regulator in <named-content content-type="genus-species">Staphylococcus aureus</named-content> That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection
title_short	Identification of a Novel LysR-Type Transcriptional Regulator in <named-content content-type="genus-species">Staphylococcus aureus</named-content> That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection
title_full	Identification of a Novel LysR-Type Transcriptional Regulator in <named-content content-type="genus-species">Staphylococcus aureus</named-content> That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection
title_fullStr	Identification of a Novel LysR-Type Transcriptional Regulator in <named-content content-type="genus-species">Staphylococcus aureus</named-content> That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection
title_full_unstemmed	Identification of a Novel LysR-Type Transcriptional Regulator in <named-content content-type="genus-species">Staphylococcus aureus</named-content> That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection
title_sort	identification of a novel lysr-type transcriptional regulator in <named-content content-type="genus-species">staphylococcus aureus</named-content> that is crucial for secondary tissue colonization during metastatic bloodstream infection
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/673e4dced8ba42758f9c0c1595d7dd52
work_keys_str_mv	AT michaelagroma identificationofanovellysrtypetranscriptionalregulatorinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentthatiscrucialforsecondarytissuecolonizationduringmetastaticbloodstreaminfection AT sarahahorst identificationofanovellysrtypetranscriptionalregulatorinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentthatiscrucialforsecondarytissuecolonizationduringmetastaticbloodstreaminfection AT sudipdas identificationofanovellysrtypetranscriptionalregulatorinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentthatiscrucialforsecondarytissuecolonizationduringmetastaticbloodstreaminfection AT brunohuettel identificationofanovellysrtypetranscriptionalregulatorinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentthatiscrucialforsecondarytissuecolonizationduringmetastaticbloodstreaminfection AT maximilianklepsch identificationofanovellysrtypetranscriptionalregulatorinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentthatiscrucialforsecondarytissuecolonizationduringmetastaticbloodstreaminfection AT thomasrudel identificationofanovellysrtypetranscriptionalregulatorinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentthatiscrucialforsecondarytissuecolonizationduringmetastaticbloodstreaminfection AT evamedina identificationofanovellysrtypetranscriptionalregulatorinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentthatiscrucialforsecondarytissuecolonizationduringmetastaticbloodstreaminfection AT martinfraunholz identificationofanovellysrtypetranscriptionalregulatorinnamedcontentcontenttypegenusspeciesstaphylococcusaureusnamedcontentthatiscrucialforsecondarytissuecolonizationduringmetastaticbloodstreaminfection
_version_	1718427093312733184

Identification of a Novel LysR-Type Transcriptional Regulator in <named-content content-type="genus-species">Staphylococcus aureus</named-content> That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection

Ejemplares similares