title: Twenty-eight divergent polysaccharide loci specifying within- and amongst-strain capsule diversity in three strains of Bacteroides fragilis.
abstract: Comparison of the complete genome sequence of Bacteroides fragilis 638R, originally isolated in the USA, was made with two previously sequenced strains isolated in the UK (NCTC 9343) and Japan (YCH46). The presence of 10 loci containing genes associated with polysaccharide (PS) biosynthesis, each including a putative Wzx flippase and Wzy polymerase, was confirmed in all three strains, despite a lack of cross-reactivity between NCTC 9343 and 638R surface PS-specific antibodies by immunolabelling and microscopy. Genomic comparisons revealed an exceptional level of PS biosynthesis locus diversity. Of the 10 divergent PS-associated loci apparent in each strain, none is similar between NCTC 9343 and 638R. YCH46 shares one locus with NCTC 9343, confirmed by mAb labelling, and a second different locus with 638R, making a total of 28 divergent PS biosynthesis loci amongst the three strains. The lack of expression of the phase-variable large capsule (LC) in strain 638R, observed in NCTC 9343, is likely to be due to a point mutation that generates a stop codon within a putative initiating glycosyltransferase, necessary for the expression of the LC in NCTC 9343. Other major sequence differences were observed to arise from different numbers and variety of inserted extra-chromosomal elements, in particular prophages. Extensive horizontal gene transfer has occurred within these strains, despite the presence of a significant number of divergent DNA restriction and modification systems that act to prevent acquisition of foreign DNA. The level of amongst-strain diversity in PS biosynthesis loci is unprecedented.
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors.forename: Sheila
authors.initials: S
authors.lastname: Patrick
authors.affiliation: Institute of Cell Biology, University of Edinburgh, Darwin Building, Kings Buildings, Edinburgh EH9 3JR, UK.
authors.forename: Garry W
authors.initials: GW
authors.lastname: Blakely
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Houston
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, UK.
authors.forename: Jane
authors.initials: J
authors.lastname: Moore
authors.affiliation: Department of Molecular and Cell Biology, University of Cape Town, South Africa.
authors.forename: Valerie R
authors.initials: VR
authors.lastname: Abratt
authors.affiliation: The Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Bertalan
authors.affiliation: The Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Cerdeño-Tárraga
authors.affiliation: The Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Quail
authors.affiliation: The Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Nicola
authors.initials: N
authors.lastname: Corton
authors.affiliation: The Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Craig
authors.initials: C
authors.lastname: Corton
authors.affiliation: The Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bignell
authors.affiliation: The Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Barron
authors.affiliation: The Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Louise
authors.initials: L
authors.lastname: Clark
authors.affiliation: The Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: The Pathogen Sequencing Unit, The Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.
authors.forename: Julian
authors.initials: J
authors.lastname: Parkhill
mesh_terms: D016667:Bacterial Capsules / Q000096:biosynthesis / Q000235:genetics*; D001441:Bacteroides fragilis / Q000235:genetics* / Q000302:isolation & purification; D055028:Comparative Genomic Hybridization; D004269:DNA, Bacterial / Q000235:genetics; D014644:Genetic Variation; D016680:Genome, Bacterial; D006801:Humans; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA
chemical_list: D004269:DNA, Bacterial