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Jeffrey N. Weiser^*, Nina Pan^*, Karin L. McGowan^*, Daniel Musher, 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 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).

J.N. Weiser is a Lucille P. Markey Charitable Trust Scholar. This work was supported by a grant from the Lucille P. Markey Charitable Trust (J.N. Weiser) and grant AI-38436 from the Public Health Service (J.N. Weiser).

Address correspondence to Jeffrey N. Weiser, 301B Johnson Pavilion, Department of Microbiology, University of Pennsylvania, Philadelphia, PA 19104-6076. Phone: 215-573-3511; Fax: 215-898-9557; E-mail: weiser{at}mail.med.upenn.edu

¹ Abbreviations used in this paper: BHI, brain heart infusion; ChoP, phosphorylcholine; CRP, C-reactive protein; ESI-MS, electrospray ionization-mass spectrometry; NHS, normal human serum; NMR, nuclear magnetic resonance.

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