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Infection and Immunity, February 2008, p. 588-600, Vol. 76, No. 2
0019-9567/08/$08.00+0     doi:10.1128/IAI.00748-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Duplicate Copies of lic1 Direct the Addition of Multiple Phosphocholine Residues in the Lipopolysaccharide of Haemophilus influenzae

Molecular Infectious Diseases Group, University of Oxford Department of Paediatrics, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, United Kingdom,¹ Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario, Canada,² Clinical Research Centre, Karolinska Institutet and University College of South Stockholm, Huddinge, Sweden,³ School of Molecular and Microbial Sciences, University of Queensland, Brisbane, Queensland, Australia⁴

Received 2 June 2007/ Returned for modification 17 July 2007/ Accepted 23 October 2007

The genes of the lic1 operon (lic1A to lic1D) are responsible for incorporation of phosphocholine (PCho) into the lipopolysaccharide (LPS) of Haemophilus influenzae. PCho plays a multifaceted role in the commensal and pathogenic lifestyles of a range of mucosal pathogens, including H. influenzae. Structural studies of the LPS of nontypeable H. influenzae (NTHI) have revealed that PCho can be linked to a hexose on any one of the oligosaccharide chain extensions from the conserved inner core triheptosyl backbone. In a collection of NTHI strains we found several strains in which there were two distinct but variant lic1D DNA sequences, genes predicted to encode the transferase responsible for directing the addition of PCho to LPS. The same isolates were also found to express concomitantly two PCho residues at distinct positions in their LPS. In one such NTHI isolate, isolate 1158, structural analysis of LPS from lic1 mutants confirmed that each of the two copies of lic1D directs the addition of PCho to a distinct location on the LPS. One position for PCho addition is a novel heptose, which is part of the oligosaccharide extension from the proximal heptose of the LPS inner core. Modification of the LPS by addition of two PCho residues resulted in increased binding of C-reactive protein and had consequential effects on the resistance of the organism to the killing effects of normal human serum compared to the effects of glycoforms containing one or no PCho. When bound, C-reactive protein leads to complement-mediated killing, indicating the potential biological significance of multiple PCho residues.

Published ahead of print on 5 November 2007.

Editor: J. N. Weiser

This article has been cited by other articles:

• Schweda, E. K.H., Twelkmeyer, B., Jianjun Li, (2008). Invited review: Profiling structural elements of short-chain lipopolysaccharide of non-typeable Haemophilus influenzae. Innate Immunity 14: 199-211 [Abstract]