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Infection and Immunity, July 2009, p. 2602-2611, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00033-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Identification of a Novel Lipopolysaccharide Core Biosynthesis Gene Cluster in Bordetella pertussis, and Influence of Core Structure and Lipid A Glucosamine Substitution on Endotoxic Activity{triangledown}

Jeroen Geurtsen,1,3 Monika Dzieciatkowska,4 Liana Steeghs,2 Hendrik-Jan Hamstra,3 Johanna Boleij,3 Kelly Broen,3 Grietsje Akkerman,3 Hassan el Hassan,3 Jianjun Li,4 James C. Richards,4 Jan Tommassen,1 and Peter van der Ley3*

Department of Molecular Microbiology,1 Department of Immunology of Infectious Diseases, Utrecht University, 3584 CH Utrecht, The Netherlands,2 Netherlands Vaccine Institute, 3720 AL Bilthoven, The Netherlands,3 Institute for Biological Sciences, National Research Council, Ottawa, Ontario, Canada K1A 0R64

Received 9 January 2009/ Returned for modification 22 February 2009/ Accepted 3 April 2009

Lipopolysaccharide (LPS), also known as endotoxin, is one of the main constituents of the gram-negative bacterial outer membrane. Whereas the lipid A portion of LPS is generally considered the main determinant for endotoxic activity, the oligosaccharide moiety plays an important role in immune evasion and the interaction with professional antigen-presenting cells. Here we describe a novel four-gene cluster involved in the biosynthesis of the Bordetella pertussis core oligosaccharide. By insertionally inactivating these genes and studying the resulting LPS structures, we show that at least two of the genes encode active glycosyltransferases, while a third gene encodes a deacetylase also required for biosynthesis of full-length oligosaccharide. In addition, we demonstrate that mutations in the locus differentially affect LPS and whole-cell endotoxic activities. Furthermore, while analyzing the mutant LPS structures, we confirmed a novel modification of the lipid A phosphate with glucosamine and found that inactivation of the responsible glycosyltransferase reduces the endotoxic activity of the LPS.

* Corresponding author. Mailing address: Netherlands Vaccine Institute, P.O. Box 457, 3720 AL Bilthoven, The Netherlands. Phone: 31-30-2742533. Fax: 31-30-2744429. E-mail: peter.van.der.ley{at}nvi-vaccin.nl

{triangledown} Published ahead of print on 13 April 2009.

Editor: A. Camilli

Infection and Immunity, July 2009, p. 2602-2611, Vol. 77, No. 7
0019-9567/09/$08.00+0     doi:10.1128/IAI.00033-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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