Structure of Extended Lipopolysaccharide Glycoforms Containing Two Globotriose Units in Haemophilus influenzae Serotype b Strain RM7004
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- 作者：Hussein Masoud ; Adè ; le Martin ; Pierre Thibault ; E. Richard Moxon ; and James C. Richards
- 刊名：Biochemistry
- 出版年：2003
- 出版时间：April 22, 2003
- 年：2003
- 卷：42
- 期：15
- 页码：4463 - 4475
- 全文大小：216K
- 年卷期：v.42,no.15(April 22, 2003)
- ISSN：1520-4995
文摘
Lipopolysaccharide (LPS) is a major virulence determinant of the human bacterial pathogenHaemophilus influenzae. Structural elucidation of the LPS from H. influenzae type b strain RM7004 wasachieved by using electrospray ionization mass spectrometry (ESI-MS) and high-field NMR techniqueson delipidated LPS and core oligosaccharide samples of LPS. It was found that the organism elaboratesa series of related LPS glycoforms having a common inner-core structure, but differing in the numberand position of attached hexose residues. LPS glycoforms containing between four and nine hexose residueswere structurally characterized. The inner-core element was determined to be L-
-D-Hepp-(1
2)-[PEA6]-L--D-Hepp-(13)-[
beta2.gif" BORDER=0 ALIGN="middle">-D-Glcp-(14)]-L--D-Hepp-(15)-[P4]--KDOp-(2, a structural feature whichhas been identified in every H. influenzae strain investigated to date. Two major groups of isomericglycoforms were characterized in which the terminal Hepp residue of the inner-core element was eithersubstituted at the O-2 position with a beta2.gif" BORDER=0 ALIGN="middle">-D-Galp residue or not. The structures of the major LPS glycoformswere found to have oligosaccharide chain extensions from O-3 of the middle Hepp residue. Glycoformscontaining five and six hexose residues were most abundant and were shown to carry the tetrasaccharideunit -D-Galp-(14)-beta2.gif" BORDER=0 ALIGN="middle">-D-Galp-(14)-beta2.gif" BORDER=0 ALIGN="middle">-D-Glcp-(14)--D-Glcp at the O-3 position of the middle heptose.This tetrasaccharide displays the globoside trisaccharide (globotriose) as a terminal epitope, a structurethat is found on many human cells (Pk blood group antigen) and which is thought to be an importantvirulence determinant for H. influenzae. LPS glycoforms were characterized that had further chain extensionfrom the beta2.gif" BORDER=0 ALIGN="middle">-D-Glcp-(1 residue of the proximal Hepp. In the fully extended LPS (Hex9/Hex8' glycoforms),both the proximal and middle heptose residues carried tetrasaccharide chains displaying terminal globotrioseepitopes. In addition, the LPS was found to carry phosphorylcholine and O-acetyl groups.
-D-Hepp-(12)-[PEA6]-L--D-Hepp-(13)-[beta2.gif" BORDER=0 ALIGN="middle">-D-Glcp-(14)]-L--D-Hepp-(15)-[P4]--KDOp-(2, a structural feature whichhas been identified in every H. influenzae strain investigated to date. Two major groups of isomericglycoforms were characterized in which the terminal Hepp residue of the inner-core element was eithersubstituted at the O-2 position with a beta2.gif" BORDER=0 ALIGN="middle">-D-Galp residue or not. The structures of the major LPS glycoformswere found to have oligosaccharide chain extensions from O-3 of the middle Hepp residue. Glycoformscontaining five and six hexose residues were most abundant and were shown to carry the tetrasaccharideunit -D-Galp-(14)-beta2.gif" BORDER=0 ALIGN="middle">-D-Galp-(14)-beta2.gif" BORDER=0 ALIGN="middle">-D-Glcp-(14)--D-Glcp at the O-3 position of the middle heptose.This tetrasaccharide displays the globoside trisaccharide (globotriose) as a terminal epitope, a structurethat is found on many human cells (Pk blood group antigen) and which is thought to be an importantvirulence determinant for H. influenzae. LPS glycoforms were characterized that had further chain extensionfrom the beta2.gif" BORDER=0 ALIGN="middle">-D-Glcp-(1 residue of the proximal Hepp. In the fully extended LPS (Hex9/Hex8' glycoforms),both the proximal and middle heptose residues carried tetrasaccharide chains displaying terminal globotrioseepitopes. In addition, the LPS was found to carry phosphorylcholine and O-acetyl groups.