title: Genomic analysis reveals the molecular basis for capsule loss in the group B Streptococcus population.
abstract: The human and bovine bacterial pathogen Streptococcus agalactiae (Group B Streptococcus, GBS) expresses a thick polysaccharide capsule that constitutes a major virulence factor and vaccine target. GBS can be classified into ten distinct serotypes differing in the chemical composition of their capsular polysaccharide. However, non-typeable strains that do not react with anti-capsular sera are frequently isolated from colonized and infected humans and cattle. To gain a comprehensive insight into the molecular basis for the loss of capsule expression in GBS, a collection of well-characterized non-typeable strains was investigated by genome sequencing. Genome based phylogenetic analysis extended to a wide population of sequenced strains confirmed the recently observed high clonality among GBS lineages mainly containing human strains, and revealed a much higher degree of diversity in the bovine population. Remarkably, non-typeable strains were equally distributed in all lineages. A number of distinct mutations in the cps operon were identified that were apparently responsible for inactivation of capsule synthesis. The most frequent genetic alterations were point mutations leading to stop codons in the cps genes, and the main target was found to be cpsE encoding the portal glycosyl transferase of capsule biosynthesis. Complementation of strains carrying missense mutations in cpsE with a wild-type gene restored capsule expression allowing the identification of amino acid residues essential for enzyme activity.
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Rosini
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Edmondo
authors.initials: E
authors.lastname: Campisi
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: De Chiara
authors.affiliation: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, Maryland, United States of America.
authors.forename: Hervé
authors.initials: H
authors.lastname: Tettelin
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rinaudo
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Toniolo
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Metruccio
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Guidotti
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Uffe B Skov
authors.initials: UB
authors.lastname: Sørensen
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Mogens
authors.initials: M
authors.lastname: Kilian
authors.affiliation: Instituto de Microbiologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Mario
authors.initials: M
authors.lastname: Ramirez
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Robert
authors.initials: R
authors.lastname: Janulczyk
authors.affiliation: Department of Computational Biology, Research and Innovation Centre, Fondazione Edmund Mach, Via E. Mach 1, San Michele all'Adige, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Donati
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Grandi
authors.affiliation: Novartis Vaccines and Diagnostics Srl, Siena, Italy.
authors.forename: Immaculada
authors.initials: I
authors.lastname: Margarit
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D002417:Cattle; D004269:DNA, Bacterial / Q000235:genetics; D005260:Female; D006801:Humans; D008414:Mastitis, Bovine / Q000382:microbiology; D058885:Multilocus Sequence Typing; D020641:Polymorphism, Single Nucleotide; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D013290:Streptococcal Infections / Q000382:microbiology / Q000662:veterinary; D013292:Streptococcus agalactiae / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial