title: In vitro and in vivo models of Staphylococcus aureus endophthalmitis implicate specific nutrients in ocular infection.
abstract: OBJECTIVE
  To define global transcriptional responses of Staphylococcus aureus and its codY mutant (CodY is a transcription regulator of virulence and metabolic genes in response to branched-chain amino acids) when growing in bovine aqueous (AH) and vitreous humor (VH) in vitro, and to investigate the impact of codY deletion on S. aureus virulence in a novel murine anterior chamber (AC) infection model.
  
  
  METHODS
  For the in vitro model, differential transcriptomic gene expression of S. aureus and its codY mutant grown in chemically defined medium (CDM), AH, and VH was analyzed. Furthermore, the strains were inoculated into the AC of mice. Changes in bacterial growth, electroretinography and inflammation scores were monitored.
  
  
  RESULTS
  Bovine AH and VH provide sufficient nutrition for S. aureus growth in vitro. Transcriptome analysis identified 72 unique open reading frames differentially regulated ≥10-fold between CDM, AH, and VH. In the AC model, we found comparable growth of the codY mutant and wild type strains in vivo. Average inflammation scores and retinal function were significantly worse for codY mutant-infected eyes at 24 h post-infection.
  
  
  CONCLUSIONS
  Our in vitro bovine AH and VH models identified likely nutrient sources for S. aureus in the ocular milieu. The in vivo model suggests that control of branched-chain amino acid availability has therapeutic potential in limiting S. aureus endophthalmitis severity.
authors.affiliation: Departments of Ophthalmology, and Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America; The Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America; Harvard Microbial Sciences Initiative, Cambridge, Massachusetts, United States of America.
authors.forename: Ama
authors.initials: A
authors.lastname: Sadaka
authors.affiliation: Departments of Ophthalmology, and Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America; The Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America; Harvard Microbial Sciences Initiative, Cambridge, Massachusetts, United States of America.
authors.forename: Kelli
authors.initials: K
authors.lastname: Palmer
authors.affiliation: Departments of Ophthalmology, and Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America; The Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America; Harvard Microbial Sciences Initiative, Cambridge, Massachusetts, United States of America.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Departments of Ophthalmology, and Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, United States of America; The Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, United States of America; Harvard Microbial Sciences Initiative, Cambridge, Massachusetts, United States of America.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gilmore
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000378:metabolism; D000818:Animals; D001082:Aqueous Humor / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002417:Cattle; D004596:Electroretinography; D009877:Endophthalmitis / Q000382:microbiology*; D015817:Eye Infections / Q000382:microbiology*; D005260:Female; D017353:Gene Deletion; D015964:Gene Expression Regulation, Bacterial; D007249:Inflammation / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D016366:Open Reading Frames; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000378:metabolism / Q000472:pathogenicity*; D059467:Transcriptome; D014774:Virulence; D014822:Vitreous Body / Q000382:microbiology
chemical_list: D000597:Amino Acids, Branched-Chain; D001426:Bacterial Proteins; C540555:CodY protein, Staphylococcus aureus; D012097:Repressor Proteins