title: Pneumococcal capsular polysaccharide structure predicts serotype prevalence.
abstract: There are 91 known capsular serotypes of Streptococcus pneumoniae. The nasopharyngeal carriage prevalence of particular serotypes is relatively stable worldwide, but the host and bacterial factors that maintain these patterns are poorly understood. Given the possibility of serotype replacement following vaccination against seven clinically important serotypes, it is increasingly important to understand these factors. We hypothesized that the biochemical structure of the capsular polysaccharides could influence the degree of encapsulation of different serotypes, their susceptibility to killing by neutrophils, and ultimately their success during nasopharyngeal carriage. We sought to measure biological differences among capsular serotypes that may account for epidemiological patterns. Using an in vitro assay with both isogenic capsule-switch variants and clinical carriage isolates, we found an association between increased carriage prevalence and resistance to non-opsonic neutrophil-mediated killing, and serotypes that were resistant to neutrophil-mediated killing tended to be more heavily encapsulated, as determined by FITC-dextran exclusion. Next, we identified a link between polysaccharide structure and carriage prevalence. Significantly, non-vaccine serotypes that have become common in vaccinated populations tend to be those with fewer carbons per repeat unit and low energy expended per repeat unit, suggesting a novel biological principle to explain patterns of serotype replacement. More prevalent serotypes are more heavily encapsulated and more resistant to neutrophil-mediated killing, and these phenotypes are associated with the structure of the capsular polysaccharide, suggesting a direct relationship between polysaccharide biochemistry and the success of a serotype during nasopharyngeal carriage and potentially providing a method for predicting serotype replacement.
authors.affiliation: Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Weinberger
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Trzciński
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Lu
authors.forename: Debby
authors.initials: D
authors.lastname: Bogaert
authors.forename: Aaron
authors.initials: A
authors.lastname: Brandes
authors.forename: James
authors.initials: J
authors.lastname: Galagan
authors.forename: Porter W
authors.initials: PW
authors.lastname: Anderson
authors.forename: Richard
authors.initials: R
authors.lastname: Malley
authors.forename: Marc
authors.initials: M
authors.lastname: Lipsitch
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000737:chemistry* / Q000235:genetics; D002353:Carrier State / Q000276:immunology / Q000382:microbiology; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D016014:Linear Models; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D011008:Pneumococcal Infections / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology*; D022242:Pneumococcal Vaccines / Q000276:immunology; D015995:Prevalence; D012703:Serotyping; D018709:Statistics, Nonparametric; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity
chemical_list: D022242:Pneumococcal Vaccines; D005632:Fructose; D005947:Glucose