title: Wall teichoic acid protects Staphylococcus aureus from inhibition by Congo red and other dyes.
abstract: OBJECTIVE
  Polyanionic polymers, including lipoteichoic acid and wall teichoic acid, are important determinants of the charged character of the staphylococcal cell wall. This study was designed to investigate the extent to which teichoic acid contributes to protection from anionic azo dyes and to identify barriers to drug penetration for development of new antibiotics for multidrug-resistant Staphylococcus aureus infection.
  
  
  METHODS
  We studied antimicrobial activity of azo dyes against S. aureus strains with or without inhibition of teichoic acid in vitro and in vivo.
  
  
  RESULTS
  We observed that inhibition of wall teichoic acid expression resulted in an ∼1000-fold increase in susceptibility to azo dyes such as Congo red, reducing its MIC from >1024 to <4 mg/L. Sensitization occurred when the first step in the wall teichoic acid pathway, catalysed by TarO, was inhibited either by mutation or by chemical inhibition. In contrast, genetic blockade of lipoteichoic acid biosynthesis did not confer Congo red susceptibility. Based on this finding, combination therapy was tested using the highly synergistic combination of Congo red plus tunicamycin at sub-MIC concentrations (to inhibit wall teichoic acid biosynthesis). The combination rescued Caenorhabditis elegans from a lethal challenge of S. aureus.
  
  
  CONCLUSIONS
  Our studies show that wall teichoic acid confers protection to S. aureus from anionic azo dyes and related compounds, and its inhibition raises the prospect of development of new combination therapies based on this inhibition.
authors.affiliation: Department of Ophthalmology, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Jennifer
authors.initials: J
authors.lastname: Campbell
authors.forename: Younghoon
authors.initials: Y
authors.lastname: Kim
authors.forename: Jonathan G
authors.initials: JG
authors.lastname: Swoboda
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Mylonakis
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
authors.forename: Michael S
authors.initials: MS
authors.lastname: Gilmore
mesh_terms: D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D001391:Azo Compounds / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000633:toxicity; D002473:Cell Wall / Q000737:chemistry* / Q000187:drug effects*; D003224:Congo Red / Q000378:metabolism / Q000633:toxicity; D006801:Humans; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000737:chemistry* / Q000187:drug effects*; D013682:Teichoic Acids / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001391:Azo Compounds; D013682:Teichoic Acids; D003224:Congo Red