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Infection and Immunity, October 2006, p. 5574-5585, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00834-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Expression of the Lipopolysaccharide-Modifying Enzymes PagP and PagL Modulates the Endotoxic Activity of Bordetella pertussis

Jeroen Geurtsen,1,2 Liana Steeghs,3 Hendrik-Jan Hamstra,2 Jan ten Hove,2 Alex de Haan,2 Betsy Kuipers,2 Jan Tommassen,1 and Peter van der Ley2*

Department of Molecular Microbiology,1 Department of Infectious Diseases and Immunology, Utrecht University, 3485 CH Utrecht,3 Netherlands Vaccine Institute, 3720 AL Bilthoven, The Netherlands2

Received 24 May 2006/ Returned for modification 19 June 2006/ Accepted 12 July 2006

Lipopolysaccharide (LPS) is one of the major constituents of the gram-negative bacterial cell envelope. Its endotoxic activity causes the relatively high reactogenicity of whole-cell vaccines. Several bacteria harbor LPS-modifying enzymes that modulate the endotoxic activity of the LPS. Here we evaluated whether two such enzymes, i.e., PagP and PagL, could be useful tools for the development of an improved and less reactogenic whole-cell pertussis vaccine. We showed that expression of PagP and PagL in Bordetella pertussis leads to increased and decreased endotoxic activity of the LPS, respectively. As expected, PagP activity also resulted in increased endotoxic activity of whole bacterial cells. However, more unexpectedly, this was also the case for PagL. This paradoxical result may be explained, in part, by an increased release of LPS, which we observed in the PagL-expressing cells.

* 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.

Editor: D. L. Burns

Infection and Immunity, October 2006, p. 5574-5585, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00834-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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