Infection and Immunity, October 2000, p. 5928-5932, Vol. 68, No. 10
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Department of Medical Microbiology, Vrije Universiteit, Medical School, 1081 BT Amsterdam, The Netherlands1; IRIS Research Center, Chiron SpA, Siena,2 and Laboratory Unit, City Hospital, Brescia,4 Italy; National Research Council, Ottawa, Canada3; and Isosep, Tullinge, Sweden5
Received 21 April 2000/Returned for modification 7 July 2000/Accepted 21 July 2000
Helicobacter pylori NCTC 11637 lipopolysaccharide (LPS)
expresses the human blood group antigens Lewis x (Lex),
Ley, and H type I. In this report, we demonstrate that the
H type I epitope displays high-frequency phase variation. One variant expressed Lex and Ley and no H type I as
determined by serology; this switch was reversible. Insertional
mutagenesis in NCTC 11637 of JHP563 (a poly(C) tract containing an open
reading frame homologous to glycosyltransferases) yielded a
transformant with a serotype similar to the phase variant. Structural
analysis of the NCTC 11637 LPS confirmed the loss of the H type I
epitope. Sequencing of JHP563 in strains NCTC 11637, an H type
I-negative variant, and an H type I-positive switchback variant showed
a C14 (gene on), C13 (gene off), and C14 tract, respectively.
Inactivation of strain G27, which expresses Lex,
Ley, H type I, and Lea, yielded a transformant
that expressed Lex and Ley. We conclude that
JHP563 encodes a
3-galactosyltransferase involved in the
biosynthesis of H type I and Lea and that phase variation
in H type I is due to C-tract changes in this gene. A second H type
I-negative variant (variant 3a) expressed Lex and
Lea and had lost both H type I and Ley
expression. Inactivation of HP093-HP094 resulted in a transformant expressing Lex and lacking Ley and H type I. Structural analysis of a mutant LPS confirmed the serological data. We
conclude that the HP093-HP094
2-fucosyltransferase (
2-FucT) gene
product is involved in the biosynthesis of both Ley and
Lex. Finally, we inactivated HP0379 in strain 3a. The
transformant had lost both Lex and Lea
expression, which demonstrates that the HP0379 gene product is both an
3- and an
4-FucT. Our data provide understanding at the molecular
level of how H. pylori is able to diversify in the host, a
requirement likely essential for successful colonization and transmission.
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