title: Capsular switching as a strategy to increase pneumococcal virulence in experimental otitis media model.
abstract: We hypothesized that capsular switch event, in which pneumococcus acquires a new capsule operon by horizontal gene transfer, may result in emergence of strains with increased virulence in acute otitis media. Using serotype 6A strain from a patient with invasive pneumococcal disease and clonally distant serotype 6C strain isolated from asymptomatic carrier we created 6A:6C (6A background with 6C capsule) capsular transformants and applied whole genome macro-restriction analysis to assess conservation of the 6A chassis. Next, we assessed complement (C3) and antibodies deposition on surface of pneumococcal cells and tested capsule recipient, capsule donor and two 6A:6C transformants for virulence in chinchilla experimental otitis media model. Both 6A:6C(1 or 2) transformants bound less C3 compared to 6C capsule-donor strain but more compared to serotype 6A capsule-recipient strain. Pneumococci were present in significantly higher proportion of ears among animals challenged with either of two 6A:6C(1 or 2) transformants compared to chinchillas infected with 6C capsule-donor strain [p < 0.001] whereas a significantly decreased proportion of ears were infected with 6A:6C(1 or 2) transformants as compared to 6A capsule-recipient strain. Our observations though limited to two serotypes demonstrate that capsular switch events can result in Streptococcus pneumoniae strains of enhanced virulence for respiratory tract infection.
authors.affiliation: Section of Pediatric Infectious Diseases, Boston Medical Center, Boston, MA 02118, USA. Electronic address: vishakha.sabharwal@bmc.org.
authors.forename: Vishakha
authors.initials: V
authors.lastname: Sabharwal
authors.affiliation: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Abbie
authors.initials: A
authors.lastname: Stevenson
authors.affiliation: Section of Pediatric Infectious Diseases, Boston Medical Center, Boston, MA 02118, USA.
authors.forename: Marisol
authors.initials: M
authors.lastname: Figueira
authors.affiliation: Section of Pediatric Infectious Diseases, Boston Medical Center, Boston, MA 02118, USA.
authors.forename: George
authors.initials: G
authors.lastname: Orthopoulos
authors.affiliation: Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Centre, Utrecht, The Netherlands.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Trzciński
authors.affiliation: Section of Pediatric Infectious Diseases, Boston Medical Center, Boston, MA 02118, USA.
authors.forename: Stephen I
authors.initials: SI
authors.lastname: Pelton
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000737:chemistry* / Q000276:immunology*; D002682:Chinchilla; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D006801:Humans; D010033:Otitis Media / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology; D011995:Recombination, Genetic; D013296:Streptococcus pneumoniae / Q000737:chemistry* / Q000276:immunology* / Q000302:isolation & purification; D014774:Virulence
chemical_list: D003176:Complement C3
keywords: Capsular switching; Pneumococcal; Virulence