title: Streptococcus pneumoniae capsule determines disease severity in experimental pneumococcal meningitis.
abstract: Streptococcus pneumoniaebacteria can be characterized into over 90 serotypes according to the composition of their polysaccharide capsules. Some serotypes are common in nasopharyngeal carriage whereas others are associated with invasive disease, but when carriage serotypes do invade disease is often particularly severe. It is unknown whether disease severity is due directly to the capsule type or to other virulence factors. Here, we used a clinical pneumococcal isolate and its capsule-switch mutants to determine the effect of capsule, in isolation from the genetic background, on severity of meningitis in an infant rat model. We found that possession of a capsule was essential for causing meningitis. Serotype 6B caused significantly more mortality than 7F and this correlated with increased capsule thickness in the cerebrospinal fluid (CSF), a stronger inflammatory cytokine response in the CSF and ultimately more cortical brain damage. We conclude that capsule type has a direct effect on meningitis severity. This is an important consideration in the current era of vaccination targeting a subset of capsule types that causes serotype replacement.
authors.affiliation: Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Bern 3001, Switzerland lucy.hathaway@ifik.unibe.ch.
authors.forename: Lucy J
authors.identifier: http://orcid.org/0000-0002-5361-5397
authors.initials: LJ
authors.lastname: Hathaway
authors.affiliation: Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Bern 3001, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Grandgirard
authors.affiliation: Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Bern 3001, Switzerland.
authors.forename: Luca G
authors.initials: LG
authors.lastname: Valente
authors.affiliation: Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Bern 3001, Switzerland.
authors.forename: Martin G
authors.initials: MG
authors.lastname: Täuber
authors.affiliation: Institute for Infectious Diseases, Faculty of Medicine, University of Bern, Bern 3001, Switzerland.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Leib
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016667:Bacterial Capsules / Q000235:genetics* / Q000276:immunology; D001921:Brain / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D016207:Cytokines / Q000134:cerebrospinal fluid / Q000276:immunology; D004195:Disease Models, Animal; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D009305:Nasopharynx; D051381:Rats; D065288:Serogroup; D012720:Severity of Illness Index; D013296:Streptococcus pneumoniae / Q000235:genetics* / Q000276:immunology
chemical_list: D016207:Cytokines
keywords: Streptococcus pneumoniae; capsule; meningitis; serotype