Phase Variation in H Type I and Lewis a Epitopes of Helicobacter pylori Lipopolysaccharide

doi:10.1128/IAI.68.10.5928-5932.2000

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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.

Phase Variation in H Type I and Lewis a Epitopes of Helicobacter pylori Lipopolysaccharide

Ben J. Appelmelk,¹^,^* M. Celeste Martino,² Eveline Veenhof,¹ Mario A. Monteiro,³ Janneke J. Maaskant,¹ Riccardo Negrini,⁴ Frank Lindh,⁵ Malcolm Perry,³ Giuseppe Del Giudice,² and Christina M. J. E. Vandenbroucke-Grauls¹

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 (Le^x), Le^y, and H type I. In this report, we demonstrate that the H typeI epitope displays high-frequency phase variation. One variantexpressed Le^x and Le^y and no H type I as determined by serology; this switch was reversible.Insertional mutagenesis in NCTC 11637 of JHP563 (a poly(C) tractcontaining 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 ofthe H type I epitope. Sequencing of JHP563 in strains NCTC 11637,an H type I-negative variant, and an H type I-positive switchbackvariant showed a C14 (gene on), C13 (gene off), and C14 tract,respectively. Inactivation of strain G27, which expresses Le^x, Le^y, H type I, and Le^a, yielded a transformant that expressed Le^x and Le^y. We conclude that JHP563 encodes a $beta$ 3-galactosyltransferase involvedin the biosynthesis of H type I and Le^a and that phase variation in H type I is due to C-tract changesin this gene. A second H type I-negative variant (variant 3a)expressed Le^x and Le^a and had lost both H type I and Le^y expression. Inactivation of HP093-HP094 resulted in a transformantexpressing Le^x and lacking Le^y and H type I. Structural analysis of a mutant LPS confirmed theserological data. We conclude that the HP093-HP094 $alpha$ 2-fucosyltransferase( $alpha$ 2-FucT) gene product is involved in the biosynthesis of bothLe^y and Le^x. Finally, we inactivated HP0379 in strain 3a. The transformanthad lost both Le^x and Le^a expression, which demonstrates that the HP0379 gene product isboth an $alpha$ 3- and an $alpha$ 4-FucT. Our data provide understanding atthe molecular level of how H. pylori is able to diversify in thehost, a requirement likely essential for successful colonizationandtransmission.

^* Corresponding author. Mailing address: Department of Medical Microbiology, Vrije Universiteit, Medical School, van der Boechorststraat7, 1081 BT Amsterdam, The Netherlands. Phone: 31 20 4448297. Fax:31 20 4448318. E-mail: BJ.Appelmelk.mm{at}med.vu.nl.

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.

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