| Autor: |
Sudip Das, Michaela Groma, Eva Medina, Martin Fraunholz, Maximilian Klepsch, Bruno Huettel, Thomas Rudel, Sarah A. Horst |
| Rok vydání: |
2020 |
| Předmět: |
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| DOI: |
10.1101/2020.06.23.166322 |
| Popis: |
Staphylococcus aureusis a common cause of bacteremia that can lead to severe complications once the bacteria exit the bloodstream and establish infection into secondary organs. Despite its clinical relevance, little is known about the bacterial factors facilitating the development of these metastatic infections. Here, we used aS. aureustransposon 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 aS. aureusstrain 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 wells as decreased transcription of genes coding for urease and components of pyrimidine nucleotides. Furthermore, we show that transcription of LTTR is repressed by glucose, induced under microaerobic conditions, and required trace amounts of copper ions. Our data thus pinpoints LTTR as an important element that enable a rapid adaptation ofS. aureusto the changing host microenvironment. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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