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J. Exp. Med.,
Volume 187, Number 4, February 16, 1998 631-640
By
From the * Department of Pediatrics and the Department of Microbiology, University of Pennsylvania
School of Medicine, Philadelphia, Pennsylvania 19104; the 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 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
phenotype).
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