title: Discovery of Streptococcus pneumoniae serotype 6 variants with glycosyltransferases synthesizing two differing repeating units.
abstract: Streptococcus pneumoniae is a persistent, opportunistic commensal of the human nasopharynx and is the leading cause of community-acquired pneumonia. It expresses an anti-phagocytic capsular polysaccharide (PS). Genetic variation of the capsular PS synthesis (cps) locus is the molecular basis for structural and antigenic heterogeneity of capsule types (serotypes). Serogroup 6 has four known members (6A-6D) with distinct serologic properties, homologous cps loci, and structurally similar PSs. cps of serotypes 6A/6B have wciNα, encoding α-1,3-galactosyltransferase, whereas serotypes 6C/6D have wciNβ encoding α-1,3-glucosyltransferase. Two atypical serogroup 6 isolates (named 6X11 and 6X12) have been discovered recently in Germany. Flow cytometric studies using monoclonal antibodies show that 6X11 has serologic properties of 6B/6D, whereas 6X12 has 6A/6C. NMR studies of their capsular PSs revealed that 6X11 and 6X12 have two different repeating units with a distribution of ~40:60 6B:6D and 75:25 6A:6C PS, respectively. Sequencing of the wciNα gene in 6X12 and 6X11 revealed single and double nucleotide substitutions, respectively, resulting in the amino acid changes A150T and D38N. Substitution of alanine with threonine at position 150 in a 6A strain was associated with hybrid serologic and chemical profiles like 6X12. The hybrid serotypes represented by 6X12 and 6X11 strains are now named serotypes 6F and 6G. Single amino acid changes in cps genes encoding glycosyltransferases can alter substrate specificities, permit biosynthesis of heterogeneous capsule repeating units, and result in new hybrid capsule types that may differ in their interaction with the immune system of the host.
authors.affiliation: Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294 and.
authors.forename: Melissa B
authors.initials: MB
authors.lastname: Oliver
authors.affiliation: the Department of Medical Microbiology, German National Reference Center for Streptococci, University Hospital Rheinisch-Westfälische Technische Hochschule, D-52074 Aachen, Germany.
authors.forename: Mark P G
authors.initials: MPG
authors.lastname: van der Linden
authors.affiliation: the Department of Medical Microbiology, German National Reference Center for Streptococci, University Hospital Rheinisch-Westfälische Technische Hochschule, D-52074 Aachen, Germany.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Küntzel
authors.affiliation: From the Departments of Microbiology and.
authors.forename: Jamil S
authors.initials: JS
authors.lastname: Saad
authors.affiliation: Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294 and; From the Departments of Microbiology and. Electronic address: nahm@uab.edu.
authors.forename: Moon H
authors.initials: MH
authors.lastname: Nahm
mesh_terms: D019943:Amino Acid Substitution; D016667:Bacterial Capsules / Q000201:enzymology* / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D056426:Genetic Loci / Q000502:physiology*; D016695:Glycosyltransferases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D020125:Mutation, Missense; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000235:genetics / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D016695:Glycosyltransferases
keywords: Amino Acid; Bispecific Transferase; Capsular Polysaccharide; Enzyme Mutation; Glycosyltransferases; Molecular Evolution; NMR; Polysaccharide; Streptococcus pneumoniae; wciN
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