title: Strain-specific virulence phenotypes of Streptococcus pneumoniae assessed using the Chinchilla laniger model of otitis media.
abstract: BACKGROUND
  Streptococcus pneumoniae [Sp] infection is associated with local and systemic disease. Our current understanding of the differential contributions of genetic strain variation, serotype, and host response to disease phenotype is incomplete. Using the chinchilla model of otitis media [OM] we investigated the disease phenotype generated by the laboratory strain TIGR4 and each of thirteen clinical strains (BS68-75, BS290, BS291, BS293, BS436 and BS437); eleven of the thirteen strains have been genomically sequenced.
  
  
  RESULTS
  For each strain 100 colony forming units were injected bilaterally into the tympanic bullae of 6 young adult chinchillas under general anesthesia. All animals were examined daily for local and systemic disease by a blinded observer. Pneumatic otoscopy was used to evaluate local disease, and behavioral assessments served as the measure of systemic disease. Virulence scoring was performed using a 4-point scale to assess four clinical parameters [severity and rapidity of local disease onset; and severity and rapidity of systemic disease onset] during a 10-day evaluation period. Highly significant variation was observed among the strains in their ability to cause disease and moribundity.
  
  
  CONCLUSIONS
  As expected, there was a significant correlation between the rapidity of systemic disease onset and severity of systemic disease; however, there was little correlation between the severity of otoscopic changes and severity of systemic disease. Importantly, it was observed that different strains of the same serotype produced as broad an array of disease phenotypes as did strains of different serotypes. We attribute these phenotypic differences among the strains to the high degree of genomic plasticity that we have previously documented.
authors.affiliation: Department of Pediatrics, Allegheny General Hospital, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Forbes
authors.forename: Edward
authors.initials: E
authors.lastname: Horsey
authors.forename: N Luisa
authors.initials: NL
authors.lastname: Hiller
authors.forename: Farrel J
authors.initials: FJ
authors.lastname: Buchinsky
authors.forename: Jay D
authors.initials: JD
authors.lastname: Hayes
authors.forename: James M
authors.initials: JM
authors.lastname: Compliment
authors.forename: Todd
authors.initials: T
authors.lastname: Hillman
authors.forename: Suzanne
authors.initials: S
authors.lastname: Ezzo
authors.forename: Kai
authors.initials: K
authors.lastname: Shen
authors.forename: Randy
authors.initials: R
authors.lastname: Keefe
authors.forename: Karen
authors.initials: K
authors.lastname: Barbadora
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Post
authors.forename: Fen Ze
authors.initials: FZ
authors.lastname: Hu
authors.forename: Garth D
authors.initials: GD
authors.lastname: Ehrlich
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism; D002682:Chinchilla / Q000382:microbiology*; D004195:Disease Models, Animal; D006801:Humans; D010033:Otitis Media / Q000235:genetics*; D010641:Phenotype; D011008:Pneumococcal Infections / Q000175:diagnosis / Q000382:microbiology*; D013045:Species Specificity; D013234:Stem Cells; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D000942:Antigens, Bacterial