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Infection and Immunity, August 2007, p. 3885-3893, Vol. 75, No. 8
0019-9567/07/$08.00+0     doi:10.1128/IAI.00212-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Pasteurella multocida Expresses Two Lipopolysaccharide Glycoforms Simultaneously, but Only a Single Form Is Required for Virulence: Identification of Two Acceptor-Specific Heptosyl I Transferases

Marina Harper,^1, John D. Boyce,^1,2, Andrew D. Cox,³ Frank St. Michael,³ Ian W. Wilkie,⁴ P. J. Blackall,⁵ and Ben Adler^1,2*

Australian Research Council Centre of Excellence in Structural and Functional Microbial Genomics, Monash University, Victoria 3800, Australia,¹ Victorian Bioinformatics Consortium, Monash University, Victoria 3800, Australia,² Institute for Biological Sciences, National Research Council, Ottawa, Ontario K1A OR6, Canada,³ Veterinary Pathology and Anatomy, University of Queensland, St. Lucia, Queensland 4072, Australia,⁴ Department of Primary Industries and Fisheries (Queensland), Animal Research Institute, Yeerongpilly 4105, Australia⁵

Received 7 February 2007/ Returned for modification 19 April 2007/ Accepted 7 May 2007

Lipopolysaccharide (LPS) is a critical virulence determinant in Pasteurella multocida and a major antigen responsible for host protective immunity. In other mucosal pathogens, variation in LPS or lipooligosaccharide structure typically occurs in the outer core oligosaccharide regions due to phase variation. P. multocida elaborates a conserved oligosaccharide extension attached to two different, simultaneously expressed inner core structures, one containing a single phosphorylated 3-deoxy-D-manno-octulosonic acid (Kdo) residue and the other containing two Kdo residues. We demonstrate that two heptosyltransferases, HptA and HptB, add the first heptose molecule to the Kdo₁ residue and that each exclusively recognizes different acceptor molecules. HptA is specific for the glycoform containing a single, phosphorylated Kdo residue (glycoform A), while HptB is specific for the glycoform containing two Kdo residues (glycoform B). In addition, KdkA was identified as a Kdo kinase, required for phosphorylation of the first Kdo molecule. Importantly, virulence data obtained from infected chickens showed that while wild-type P. multocida expresses both LPS glycoforms in vivo, bacterial mutants that produced only glycoform B were fully virulent, demonstrating for the first time that expression of a single LPS form is sufficient for P. multocida survival in vivo. We conclude that the ability of P. multocida to elaborate alternative inner core LPS structures is due to the simultaneous expression of two different heptosyltransferases that add the first heptose residue to the nascent LPS molecule and to the expression of both a bifunctional Kdo transferase and a Kdo kinase, which results in the initial assembly of two inner core structures.

Published ahead of print on 21 May 2007.

Editor: V. J. DiRita

These authors contributed equally to the work.

This article has been cited by other articles:

• Harper, M., Cox, A., St. Michael, F., Parnas, H., Wilkie, I., Blackall, P. J., Adler, B., Boyce, J. D. (2007). Decoration of Pasteurella multocida Lipopolysaccharide with Phosphocholine Is Important for Virulence. J. Bacteriol. 189: 7384-7391 [Abstract] [Full Text]