Show simple item record

dc.contributor.authorGroma, Michaela
dc.contributor.authorHorst, Sarah A
dc.contributor.authorDas, Sudip
dc.contributor.authorHuettel, Bruno
dc.contributor.authorKlepsch, Maximilian
dc.contributor.authorRudel, Thomas
dc.contributor.authorMedina, Eva
dc.contributor.authorFraunholz, Martin
dc.date.accessioned2020-09-10T08:38:13Z
dc.date.available2020-09-10T08:38:13Z
dc.date.issued2020-08-25
dc.identifier.citationmBio. 2020;11(4):e01646-20. Published 2020 Aug 25.en_US
dc.identifier.pmid32843554
dc.identifier.doi10.1128/mBio.01646-20
dc.identifier.urihttp://hdl.handle.net/10033/622435
dc.description.abstractStaphylococcus 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.IMPORTANCEStaphylococcus 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.en_US
dc.language.isoenen_US
dc.publisherASMen_US
dc.rightsAttribution-NonCommercial-ShareAlike 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectStaphylococcus aureusen_US
dc.subjectmetabolic adaptationen_US
dc.subjectsecondary site infectionen_US
dc.subjecttranscriptional regulationen_US
dc.titleIdentification of a Novel LysR-Type Transcriptional Regulator in Staphylococcus aureus That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection.en_US
dc.typeArticleen_US
dc.identifier.eissn2150-7511
dc.contributor.departmentHZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.en_US
dc.identifier.journalmBioen_US
dc.source.volume11
dc.source.issue4
refterms.dateFOA2020-09-10T08:38:14Z
dc.source.journaltitlemBio
dc.source.countryUnited States


Files in this item

Thumbnail
Name:
Groma et al.pdf
Size:
1.499Mb
Format:
PDF
Description:
Open Access publication

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-ShareAlike 4.0 International
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-ShareAlike 4.0 International