PHOSPHORYLCHOLINE ON THE LIPOPOLYSACCHARIDE OF HAEMOPHILUS-INFLUENZAECONTRIBUTES TO PERSISTENCE IN THE RESPIRATORY-TRACT AND SENSITIVITY TO SERUM KILLING MEDIATED BY C-REACTIVE PROTEIN

Haemophilus influenzae undergoes phase variation in expression of the phosphorylcholine (ChoP) epitope, a structure present on several invas ive pathogens residing in the human respiratory tract. In this study, structural analysis comparing organisms with and without this epitope confirmed thai variants differ in the presence of ChoP on the cell sur face-exposed outer core of the lipopolysaccharide. During nasopharynge al carriage in infant rats, there was a gradual selection for H. influ enzae variants that express ChoP. In addition, genotypic analysis of t he molecular switch that controls phase variation predicted that the C hoP(+) phenotype was predominant in H. influenzae in human respiratory tract secretions. However, ChoP(+) variants of nontypable H. influenz ae were more sensitive to the bactericidal activity of human serum unr elated to the presence of naturally acquired antibody to ChoP. Serum b actericidal activity required the binding of C-reactive protein (CRP) with subsequent activation of complement through the classical pathway . Results of this study suggested that thr ability of H. influenzae to vary expression of this unusual bacterial structure may correlate wit h its ability both to persist on the mucosal surface (ChoP(+) phenotyp e) and to cause invasive infection by evading innate immunity mediated by CRP (ChoP(-) phenotype).