Identification of a Novel LysR-Type Transcriptional Regulator in Staphylococcus aureus That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection.

Details

Serval ID
serval:BIB_B43A51BE9F68
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of a Novel LysR-Type Transcriptional Regulator in Staphylococcus aureus That Is Crucial for Secondary Tissue Colonization during Metastatic Bloodstream Infection.
Journal
mBio
Author(s)
Groma M., Horst S.A., Das S., Huettel B., Klepsch M., Rudel T., Medina E., Fraunholz M.
ISSN
2150-7511 (Electronic)
Publication state
Published
Issued date
25/08/2020
Peer-reviewed
Oui
Volume
11
Number
4
Pages
e01646-20
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
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.
Keywords
Animals, Bacteremia/microbiology, Bacterial Proteins/genetics, Bacterial Proteins/metabolism, Female, Gene Expression Regulation, Bacterial, Mice, Mice, Inbred C57BL, Specific Pathogen-Free Organisms, Staphylococcal Infections/microbiology, Staphylococcus aureus/genetics, Staphylococcus aureus/pathogenicity, Transcription Factors/genetics, Transcription Factors/metabolism, Transcription, Genetic, Virulence, Virulence Factors, Staphylococcus aureus, metabolic adaptation, secondary site infection, transcriptional regulation
Pubmed
Web of science
Open Access
Yes
Create date
10/09/2020 11:36
Last modification date
29/07/2021 6:39
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