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LIPOPOLYSACCHARIDES FROM PATHOGENIC BACTERIA: STRUCTURE AND FUNCTION

 

Higruppenvt07

Our group spring 2007, from left to right: Varvara Viteazeva, PhD student, Peter Burström,

master student,Elke Schweda, professor, Susanna Lundström, PhD student,Mikael Engskog,

PhD student,BrigitteTwelkmeyer, Phd student

 

Contact: Elke Schweda, PhD, professor

Karolinska Institutet, Clinical Research Centre

NOVUM, S-141 86 Huddinge

Tel.: 46 8 585 838 23; Fax: 46 8 585 838 20
E-mail
 

Carbohydrates on the surface of many pathogenic bacteria are active in immunological and other biological systems.
A study of these molecules gives insight into the relationship between chemical structure and function which is important when it comes to development of better diagnostic tools and new therapeutic strategies against bacterial diseases.

Our group is active in the field of analytical carbohydrate chemistry and uses a combination of chemical methods and state-of-the-art physicochemical methods as electrospray ionization mass spectrometry (ESI-MS), MS-MS and NMR to study lipopolysaccharides from Haemophilus influenzae and others.

 

Haemophilus influenzae is a frequent cause of upper and lower respiratory tract infections, meningitis and otitis media. Lipopolysaccharide (LPS) is an essential and integral surface component of H. influenzae and a major virulence determinant. A feature of H. influenzae LPS is that surface exposed epitopes of the oligosaccharide are subject to high-frequency on-off switching of expression (phase variation). This heterogeneity may be an advantage to the bacteria allowing them to better confront different host compartments and microenvironments and to survive the host immune respons. Determination of structure is crucial to understanding the biology of H. influenzae and its role in virulence.

 

 

 

 

Molecular structural studies of LPS from mutant and wild-type strains of H. influenzae have resulted in a structural model consisting of a conserved triheptosyl inner-core moiety in which each of the heptose residues can provide a point for elongation by hexose-containing oligosaccharide chains or for attachment of non-carbohydrate substituents (Structure 1).
The availability of the complete genome sequence of H. influenzae strain Rd facilitated a comprehensive study of multiple LPS biosynthetic loci in H. influenzae. Many predicted gene functions are now correlated with particular steps in the synthesis of the LPS by analysis of LPS structure from the appropriate mutant strains.

Structure

 

 

 

fig1

 

 

 

 

Fig.1

Space-filling and ball-and-stick models of the oligosaccharide region of LPS from non-typeable Haemophilus influenzae strain 1124. The conformation shown represents the Hex7 glycoform found in this strain. KDO (grey) is linked to a heptose trisaccharide (red) and each heptose has attached side-chains consisting of glucose (green), galactose (blue), galactoseamin (turquoise) and/or phospoethanolamine (yellow). Phosphocholine is shown in orange.

 

 

Selected references:

 

  1. Specific amino acids of the glycosyltransferase LpsA direct the addition of glucose or galactose to the terminal inner-core heptose of H. influenzae LPS.
    Mary E. Deadman, Susanna L. Lundström, Elke. K. H. Schweda, E. Richard Moxon and Derek W. Hood.
    J. Biol. Chem., 281 (2006) 29455-29467.

  2. Structural characterization of sialylated glycoforms of H. influenzae by electrospray mass spectrometry: fragmentation of protonated and sodiated O-deacylated lipopolysaccharides.
    Jianjun Li, Monika Dzieciatkowska, Derek W. Hood, Andrew D. Cox, Elke K. H. Schweda, E. Richard Moxon and James C. Richards.
    Rapid Commun. Mass Spectrom., 21 (2007) 952-960.

  3. Expression and structural diversity of the lipopolysaccharide of Haemophilus influenzae: Implication in virulence.
    Elke K. H. Schweda, James C. Richards, Derek W. Hood and E. Richard Moxon.
    Int J Med Microbiol., 297 (2007) 297-306.

  4. A Haemophilus influenzae strain associated with Fischer Syndrome expresses a novel disialylated ganglioside mimic.
    R. Scott Houliston, Michiaki Koga, Jianjun Li, Harold C. Jarrell, James C. Richards, Varvara Vitiazeva, Elke K. H. Schweda, Nobuhiro Yuki and Michel Gilbert.
    Biochemistry, 46 (2007) 8164-8171.

  5. Novel globoside-like oligosaccharide expression patterns in nontypeable Haemophilus influenzae lipopolysaccharide.

    Susanna L. Lundström, Brigitte Twelkmeyer, Malin K. Sagemark, Jianjun Li, James C. Richards, Derek W. Hood, E. Richard Moxon, Elke K. H. Schweda.
    FEBS Journal, 274 (2007) 4886-4903.

  6. Dublicate copies of lic1 direct the addition of multiple phosphocholine residues in the lipopolysaccharide of Haemophilus influenzae.
    Kate L. Fox, Jianjun Li, Elke K.H. Schweda, Varvara Vitiazeva, Katherine Makepeace, Michael P. Jennings, E. Richard Moxon and Derek W. Hood.
    Infect. Immun., 76 (2008) 588-600.

  7. Characterization of intact lipopolysaccharide from the Haemophilus influenzae strain RM118 using electrophoresis-assisted open-tubular liquid chromatography-mass spectrometry.
    Monika Dzieciatkowska, Elke K. H. Schweda, E. Richard Moxon, James C. Richards, Jianjun Li.
    Electrophoresis, 29 (2008) 2171-2181.

  8. Application of capillary electrophoresis mass spectrometry and liquid chromatography multiple-step tandem electrospray mass spectrometry to profile glycoform expression during Haemophilus influenzae pathogenesis in the chinchilla model of experimental otitis media.
    Susanna L. Lundström, Jianjun Li, Martin Månsson, Maridol Figuera, Magali Leroy, Richard Goldstein, Derek W. Hood, E. Richard Moxon, James C. Richards, Elke K. H. Schweda.
    Infect. Immun., 76 (2008) 3255-67.

  9. Structural analysis of the lipopolysaccharide from non-typeable Haemophilus influenzae strain R2846.
    Susanna L. Lundström, Jianjun Li, Mary E. Deadman, Derek W. Hood, E. Richard Moxon, Elke K. H. Schweda.
    Biochemistry, 47 (2008) 6025-38.

  10. Profiling structural elements of short-chain lipopolysaccharide of non-typeable Haemophilus influenzae.
    Elke K. H. Schweda, Brigitte Twelkmeyer and Jianjun Li.
    Innate Immunity, 14 (2008) 199-211.

  11. Rapid method for sensitive screening of oligosaccharide epitopes in the lipooligosaccharide from Campylobacter jejuni strains isolated from Guillain-Barré syndrome and Miller Fischer syndrome parients.
    Monika Dzieciatkowska, Xin Liu, Astrid Heikema, R. Scott Houliston, Alex van Belkum, Elke K. H. Schweda, Michel Gilbert, James C. Richards and Jianjun Li.
    Journal of Clinical Microbiology, in press

 

Uppdaterat 2008-09-04