title: In vivo gene expression in a Staphylococcus aureus prosthetic joint infection characterized by RNA sequencing and metabolomics: a pilot study.
abstract: BACKGROUND
  Staphylococcus aureus gene expression has been sparsely studied in deep-sited infections in humans. Here, we characterized the staphylococcal transcriptome in vivo and the joint fluid metabolome in a prosthetic joint infection with an acute presentation using deep RNA sequencing and nuclear magnetic resonance spectroscopy, respectively. We compared our findings with the genome, transcriptome and metabolome of the S. aureus joint fluid isolate grown in vitro.
  
  
  RESULTS
  From the transcriptome analysis we found increased expression of siderophore synthesis genes and multiple known virulence genes. The regulatory pattern of catabolic pathway genes indicated that the bacterial infection was sustained on amino acids, glycans and nucleosides. Upregulation of fermentation genes and the presence of ethanol in joint fluid indicated severe oxygen limitation in vivo.
  
  
  CONCLUSIONS
  This single case study highlights the capacity of combined transcriptome and metabolome analyses for elucidating the pathogenesis of prosthetic infections of major clinical importance.
authors.affiliation: Center for Microbial Communities, Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajersvej 7H, 9220, Aalborg, Denmark.|The Danish Technological Institute, Life Science Division, Aarhus, Denmark.
authors.forename: Yijuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Center for Microbial Communities, Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajersvej 7H, 9220, Aalborg, Denmark.
authors.forename: Raluca Georgiana
authors.initials: RG
authors.lastname: Maltesen
authors.affiliation: Center for Microbial Communities, Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajersvej 7H, 9220, Aalborg, Denmark.|Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Lone Heimann
authors.initials: LH
authors.lastname: Larsen
authors.affiliation: Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark.|Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Henrik Carl
authors.initials: HC
authors.lastname: Schønheyder
authors.affiliation: Section for Molecular Diagnostics, Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark.
authors.forename: Vang Quy
authors.initials: VQ
authors.lastname: Le
authors.affiliation: Center for Microbial Communities, Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajersvej 7H, 9220, Aalborg, Denmark.
authors.forename: Jeppe Lund
authors.initials: JL
authors.lastname: Nielsen
authors.affiliation: Center for Microbial Communities, Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajersvej 7H, 9220, Aalborg, Denmark.
authors.forename: Per Halkjær
authors.initials: PH
authors.lastname: Nielsen
authors.affiliation: Center for Microbial Communities, Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajersvej 7H, 9220, Aalborg, Denmark.|The Danish Technological Institute, Life Science Division, Aarhus, Denmark.
authors.forename: Trine Rolighed
authors.initials: TR
authors.lastname: Thomsen
authors.affiliation: Center for Microbial Communities, Department of Chemistry and Bioscience, Aalborg University, Fredrik Bajersvej 7H, 9220, Aalborg, Denmark. kln@bio.aau.dk.
authors.forename: Kåre Lehmann
authors.initials: KL
authors.lastname: Nielsen
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods*; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D006801:Humans; D007720:Knee Prosthesis / Q000009:adverse effects*; D055432:Metabolomics / Q000379:methods*; D010865:Pilot Projects; D016459:Prosthesis-Related Infections / Q000382:microbiology*; D017423:Sequence Analysis, RNA / Q000379:methods*; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000235:genetics / Q000302:isolation & purification* / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins
keywords: In vivo gene expression; Joint infection; Metabolism; Metabolomics; NMR; Prosthesis; RNA-seq; Siderophore; Staphylococcus aureus; Virulence