The position of phosphorylcholine on the lipopolysaccharide of Haemophilusinfluenzae affects binding and sensitivity to C-reactive protein-mediated killing

The lid locus of Haemophilus influenzae controls the incorporation of envir onmental choline into lipopolysaccharide (LPS) as phosphorylcholine (ChoP) as well as the phase variation of this structure. Chop is the target of an acute phase reactant in serum, C-reactive protein (CRP), which mediates kil ling through the activation of complement when bound to the organism. Struc tural analysis of the oligosaccharide region of the H. influenzae LPS showe d that Chop is linked to different hexose residues on different chain exten sions in strains Ed and Eagan. Differences in the molecular environment of Chop affect the epitope defined by monoclonal antibody 12D9 and were associ ated with polymorphisms within LicD, a putative diphosphonucleoside choline transferase. Exchanging the licD genes between the two strains with Chop o n different chain extensions was sufficient to switch its position. Allelic variants with ChoP on a hexose on heptose III rather than heptose I were s ensitive to CRP-mediated serum bactericidal activity regardless of the gene tic background. Differences in CRP-mediated killing correlated with differe nces in the binding of CRP from human serum to whole bacteria. This suggest s that, in addition to the mechanism involving phase variation, the structu ral rearrangements within the oligosaccharide contribute to evasion of inna te and acquired immunity.