title: Polysaccharide Capsule Composition of Pneumococcal Serotype 19A Subtypes Is Unaltered among Subtypes and Independent of the Nutritional Environment.
abstract: Serotype 19A strains have emerged as a cause of invasive pneumococcal disease after the introduction of the 7-valent pneumococcal conjugate vaccine (PCV7), and serotype 19A has now been included in the recent 13-valent vaccine (PCV13). Genetic analysis has revealed at least three different capsular serotype 19A subtypes, and nutritional environment-dependent variation of the 19A capsule structure has been reported. Pneumococcal vaccine effectiveness and serotyping accuracy might be impaired by structural differences in serotype 19A capsules. We therefore analyzed the distribution of 19A subtypes collected within a Swiss national surveillance program and determined capsule composition under different nutritional conditions with high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and nuclear magnetic resonance (NMR) spectroscopy. After the introduction of PCV7, a significant relative increase of subtype 19A-II and decrease of 19A-I occurred. Chemical analyses showed no difference in the composition as well as the linkage of 19A subtype capsular saccharides grown in defined and undefined growth media, which is consistent with a trisaccharide repeat unit composed of rhamnose, N-acetyl-mannosamine, and glucose. In summary, our study suggests that no structural variance dependent of the nutritional environment or the subtype exists. The serotype 19A subtype shift observed after the introduction of the PCV7 can therefore not be explained by selection of a capsule structure variant. However, capsule composition analysis of emerging 19A clones is recommended in cases where there is no other explanation for a selective advantage, such as antibiotic resistance or loss or acquisition of other virulence factors.
authors.affiliation: Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Silvio D
authors.identifier: http://orcid.org/0000-0001-9492-9088
authors.initials: SD
authors.lastname: Brugger
authors.affiliation: Institute for Infectious Diseases, University of Bern, Bern, Switzerland.|Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors.forename: Lukas J
authors.initials: LJ
authors.lastname: Troxler
authors.affiliation: Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Susanne
authors.initials: S
authors.lastname: Rüfenacht
authors.affiliation: Institute for Infectious Diseases, University of Bern, Bern, Switzerland.|Department of General Internal Medicine, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Pascal M
authors.initials: PM
authors.lastname: Frey
authors.affiliation: Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Morand
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Giessen, Giessen, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Geyer
authors.affiliation: Institute for Infectious Diseases, University of Bern, Bern, Switzerland.|Department of Infectious Diseases, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Mühlemann
authors.affiliation: ZHAW Zurich University of Applied Sciences, School of Life Sciences and Facility Management, Institute for Chemistry and Biotechnology, Wädenswil, Switzerland.
authors.forename: Stefan
authors.initials: S
authors.lastname: Höck
authors.affiliation: Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Thormann
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern, Bern, Switzerland.
authors.forename: Julien
authors.initials: J
authors.lastname: Furrer
authors.affiliation: Institute for Infectious Diseases, University of Bern, Bern, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Christen
authors.affiliation: Institute for Infectious Diseases, University of Bern, Bern, Switzerland markus.hilty@ifik.unibe.ch.|Department of Infectious Diseases, Bern University Hospital, Inselspital, University of Bern, Bern, Switzerland.
authors.forename: Markus
authors.identifier: http://orcid.org/0000-0002-2418-6474
authors.initials: M
authors.lastname: Hilty
mesh_terms: D016667:Bacterial Capsules / Q000737:chemistry*; D002853:Chromatography, Liquid; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011008:Pneumococcal Infections / Q000382:microbiology*; D011134:Polysaccharides / Q000737:chemistry*; D011159:Population Surveillance; D012044:Regression Analysis; D065288:Serogroup; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000502:physiology*
chemical_list: D011134:Polysaccharides