title: Role of wall teichoic acids in Staphylococcus aureus endophthalmitis.
abstract: OBJECTIVE
  Wall teichoic acids (WTAs) are major polyanionic polymer components of the cell wall of Staphylococcus aureus. However, little is known about their role at the host-pathogen interface, especially in endophthalmitis. This study was designed to investigate the extent to which WTAs contribute to the pathogenicity of S. aureus in models of endophthalmitis and to determine whether there would be value in targeting their biosynthesis as a new therapeutic approach.
  
  
  METHODS
  S. aureus RN6390 and its isogenic WTA-null mutant (RN6390ΔtarO) were used to evaluate the role of WTAs in endophthalmitis. RN6390 and RN6390ΔtarO were cultured in bovine vitreous humor (VH) in vitro or inoculated into the vitreous chamber of C57B6 mice. Changes in the number of bacteria, organ function as determined by electroretinography (ERG), and histopathologic changes were assessed throughout the course of infection. In addition, the efficacy of WTA biosynthesis inhibitors in VH in vitro was examined.
  
  
  RESULTS
  It was observed that a component of VH synergized with WTA biosynthesis inhibitors in vitro and killed the S. aureus. This effect was also seen when mutants incapable of expressing WTA were exposed to VH. The killing activity of VH was lost on treatment with a protease inhibitor. RN6390ΔtarO could not survive in mouse eyes and did not affect organ function, nor was it able to establish endophthalmitis.
  
  
  CONCLUSIONS
  WTAs are essential cellular constituents for the manifestation of virulence by S. aureus in endophthalmitis, and appears to be a viable target for treating the endophthalmitis caused by S. aureus strains.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts 02114, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Jennifer
authors.initials: J
authors.lastname: Campbell
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Swoboda
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gilmore
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002417:Cattle; D002473:Cell Wall; D015169:Colony Count, Microbial; D004596:Electroretinography; D009877:Endophthalmitis / Q000382:microbiology*; D015818:Eye Infections, Bacterial / Q000382:microbiology*; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D013203:Staphylococcal Infections / Q000382:microbiology*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000302:isolation & purification / Q000472:pathogenicity*; D013682:Teichoic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017334:Teicoplanin / Q000494:pharmacology; D014415:Tunicamycin / Q000494:pharmacology; D014774:Virulence; D014822:Vitreous Body / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D013682:Teichoic Acids; D014415:Tunicamycin; D017334:Teicoplanin