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Originally published In Press as doi:10.1074/jbc.M108574200 on December 7, 2001
J. Biol. Chem., Vol. 277, Issue 8, 5785-5795, February 22, 2002
Phenotypic Variation in Molecular Mimicry between
Helicobacter pylori Lipopolysaccharides and Human Gastric
Epithelial Cell Surface Glycoforms
ACID-INDUCED PHASE VARIATION IN LEWISX
AND LEWISY EXPRESSION BY H. PYLORI
LIPOPOLYSACCHARIDES*
Anthony P.
Moran ,
Yuriy A.
Knirel§¶,
Sof'ya N.
Senchenkova§¶,
Göran
Widmalm ,
Sean O.
Hynes , and
Per-Erik
Jansson§**
From the Department of Microbiology,
National University of Ireland, Galway, Ireland,
§ Karolinska Institute, Clinical Research Centre, Huddinge
University Hospital, Novum, S-141 86 Huddinge, Sweden, ¶ N.
D. Zelinsky Institute of Organic Chemistry, Russian Academy of
Sciences, 119991 Moscow, Russia, and Department of Organic
Chemistry, Arrhenius Laboratory, Stockholm University,
S-10691 Stockholm, Sweden
Helicobacter pylori is
an important gastroduodenal pathogen of humans whose survival in the
gastric environment below pH 4 is dependent on bacterial production of
urease, whereas above pH 4 urease-independent mechanisms are involved
in survival, but that remain to be elucidated fully. Previous
structural investigations on the lipopolysaccharides (LPSs) of H. pylori have shown that the majority of these surface glycolipids
express partially fucosylated, glucosylated, or galactosylated
N-acetyllactosamine (LacNAc) O-polysaccharide chains
containing Lewisx (Lex) and/or
Lewisy (Ley), although some strains also
express type 1 determinants, Lewisa, Lewisb,
and H-1 antigen. In this study, we investigated acid-induced changes in
the structure and composition of LPS and cellular lipids of the
genome-sequenced strain, H. pylori 26695. When grown in liquid medium at pH 7, the O-chain consisted of a type 2 LacNAc polysaccharide, which was glycosylated with -L-fucose at
O-3 of the majority of N-acetylglucosamine residues forming
Lex units, including chain termination by a Lex
unit. However, growth in liquid medium at pH 5 resulted in production of a more complex O-chain whose backbone of type 2 LacNAc units was
partially glycosylated with -L-fucose, thus forming
Lex, whereas the majority of the nonfucosylated
N-acetylglucosamine residues were substituted at O-6 by
-D-galactose residues, and the chain was terminated by a
Ley unit. In contrast, detailed chemical analysis of the
core and lipid A components of LPS and analysis of cellular lipids did not show significant differences between H. pylori 26695 grown at pH 5 and 7. Although putative molecular mechanisms affecting Lex and Ley expression have been investigated
previously, this is the first report identifying an environmental
trigger inducing phase variation of Lex and Ley
in H. pylori that can aid adaptation of the bacterium
to its ecological niche.
*
This work was supported by The International Association for
the Promotion of Cooperation with Scientists from the New Independent States of the Former Soviet Union Grant 97-0695, Irish Health Research Board (to A. P. M.), Millennium Research Fund (to
A. P. M.), Swedish Research Council (to P. E. J. and G. W.), Royal Swedish Academy of Sciences (to P. E. J.), and Karolinska Institute fellowships (to Y. A. K. and S. N. S.). This work was presented in
part at the 19th International Carbohydrate Symposium, August 9-14,
1998 in San Diego, CA.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
**
To whom correspondence should be addressed. Tel.: 46-8-58583821;
Fax: 46-8-58583820; E-mail: pererik.jansson@kfc.hs.sll.se.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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