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Infection and Immunity, October 2008, p. 4431-4438, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.00321-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

The Sialylated Lipooligosaccharide Outer Core in Campylobacter jejuni Is an Important Determinant for Epithelial Cell Invasion{triangledown}

Rogier Louwen,1* Astrid Heikema,1 Alex van Belkum,1 Alewijn Ott,1,{dagger} Michel Gilbert,3 Wim Ang,1,{ddagger} Hubert P. Endtz,1 Mathijs P. Bergman,1,{ddagger} and Edward E. Nieuwenhuis2

Departments of Medical Microbiology and Infectious Diseases,1 Pediatrics, Erasmus MC, Rotterdam, The Netherlands,2 Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada3

Received 11 March 2008/ Returned for modification 20 April 2008/ Accepted 8 July 2008

Campylobacter jejuni is a frequent cause of bacterial gastroenteritis worldwide. Lipooligosaccharide (LOS) has been identified as an important virulence factor that may play a role in microbial adhesion and invasion. Here we specifically address the question of whether LOS sialylation affects the interaction of C. jejuni with human epithelial cells. For this purpose, 14 strains associated with Guillain-Barré syndrome (GBS), 34 enteritis-associated strains, the 81-176 reference strain, and 6 Penner serotype strains were tested for invasion of two epithelial cell lines. C. jejuni strains expressing sialylated LOS (classes A, B, and C) invaded cells significantly more frequently than strains expressing nonsialylated LOS (classes D and E) (P < 0.0001). To further explore this observation, we inactivated the LOS sialyltransferase (Cst-II) via knockout mutagenesis in three GBS-associated C. jejuni strains expressing sialylated LOS (GB2, GB11, and GB19). All knockout strains displayed significantly lower levels of invasion than the respective wild types. Complementation of a {Delta}cst-II mutant strain restored LOS sialylation and reset the invasiveness to wild-type levels. Finally, formalin-fixed wild-type strains GB2, GB11 and GB19, but not the isogenic {Delta}cst-II mutants that lack sialic acid, were able to inhibit epithelial invasion by viable GB2, GB11, and GB19 strains. We conclude that sialylation of the LOS outer core contributes significantly to epithelial invasion by C. jejuni and may thus play a role in subsequent postinfectious pathologies.

* Corresponding author. Mailing address: Department of Medical Microbiology and Infectious Diseases, Erasmus MC, University Medical Center Rotterdam, 's-Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands. Phone: 31-10-7032176. Fax: 31-10-7043875. E-mail: r.louwen{at}erasmusmc.nl

{triangledown} Published ahead of print on 21 July 2008.

Editor: J. B. Bliska

{dagger} Present address: Laboratory for Infectious Diseases, Groningen, The Netherlands.

{ddagger} Present address: Department of Medical Microbiology, Vrije Universiteit, Amsterdam, The Netherlands.

Infection and Immunity, October 2008, p. 4431-4438, Vol. 76, No. 10
0019-9567/08/$08.00+0     doi:10.1128/IAI.00321-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Habib, I., Louwen, R., Uyttendaele, M., Houf, K., Vandenberg, O., Nieuwenhuis, E. E., Miller, W. G., van Belkum, A., De Zutter, L. (2009). Correlation between Genotypic Diversity, Lipooligosaccharide Gene Locus Class Variation, and Caco-2 Cell Invasion Potential of Campylobacter jejuni Isolates from Chicken Meat and Humans: Contribution to Virulotyping. Appl. Environ. Microbiol. 75: 4277-4288 [Abstract] [Full Text]  


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