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J. Exp. Med., Volume 187, Number 4, February 16, 1998 631-640

Phosphorylcholine on the Lipopolysaccharide of Haemophilus influenzae Contributes to Persistence in the Respiratory Tract and Sensitivity to Serum Killing Mediated by C-reactive Protein

By Jeffrey N. Weiser,* Nina Pan,* Karin L. McGowan,* Daniel Musher,Dagger Adèle Martin,§ and Jim Richards§

From the * Department of Pediatrics and the Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104; the Dagger  Infectious Disease Section, Veterans Administration Medical Center, Houston, Texas 77211; and the § Institute for Biological Sciences, National Research Council of Canada, Ontario, Canada K1A OR6

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


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