title: Inactivation of specific Pseudomonas aeruginosa biofilm factors does not alter virulence in infected cholesteatomas.
abstract: OBJECTIVE
  When experimental cholesteatomas are infected with Pseudomonas aeruginosa (PA) mutants lacking factors associated with the formation of biofilms, host defenses are more effective against these strains when compared with wild-type strains (PAO1 and OPPA8) in preventing tissue destruction.
  
  
  BACKGROUND
  Previous studies have identified biofilms within chronically infected aural cholesteatomas. These infected cholesteatomas are associated with increased tissue destruction. Because biofilms are highly resistant to host defenses leading to prolonged infection, we propose that the biofilm phenotype of P. aeruginosa may be a virulence factor leading to persistence of infection and increased tissue destruction.
  
  
  METHODS
  Aural cholesteatomas were induced in Mongolian gerbils. At the time of induction, the ear canals were inoculated with wild-type (PAO1 and OPPA8) and biofilm-deficient (PAO1 ΔpilA, PAO1 algD::aacC1 and PAO1 galU::aacC1) strains of P. aeruginosa. After 8 weeks, the size of the cholesteatomas and levels of bone destruction and deposition were measured using microCT scanning and double fluorochrome bone labeling.
  
  
  RESULTS
  Infected cholesteatomas resulted in increased growth, bone destruction, and bone deposition when compared with vehicle-only controls. We observed no differences between the wild-type (biofilm forming) and the biofilm-deficient strains of P. aeruginosa.
  
  
  CONCLUSIONS
  Our hypothesis that biofilm formation is a virulence factor in cholesteatomas infected with P. aeruginosa was not supported. A number of interpretations of these data are reasonable. It is possible that biofilms are not critical in infected cholesteatomas. Alternatively, the mutants that are deficient in generating biofilms in vitro may be able to form effective biofilms in vivo using alternative pathways.
authors.affiliation: *Departments of Otolaryngology and †Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri, U.S.A.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Chole
authors.forename: Patricia M
authors.initials: PM
authors.lastname: Gagnon
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Vogel
mesh_terms: D000818:Animals; D018441:Biofilms; D018424:Cholesteatoma, Middle Ear / Q000382:microbiology*; D004195:Disease Models, Animal; D005849:Gerbillinae; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology; D014774:Virulence; D037521:Virulence Factors / Q000633:toxicity*
chemical_list: D037521:Virulence Factors