title: Phosphorylcholine allows for evasion of bactericidal antibody by Haemophilus influenzae.
abstract: The human pathogen Haemophilus influenzae has the ability to quickly adapt to different host environments through phase variation of multiple structures on its lipooligosaccharide (LPS), including phosphorylcholine (ChoP). During colonization with H. influenzae, there is a selection for ChoP+ phase variants. In a murine model of nasopharyngeal colonization, this selection is lost in the absence of adaptive immunity. Based on previous data highlighting the importance of natural antibody in limiting H. influenzae colonization, the effect of ChoP expression on antibody binding and its bactericidal activity was investigated. Flow cytometric analysis revealed that ChoP+ phase variants had decreased binding of antibody to LPS epitopes compared to ChoP- phase variants. This difference in antibody binding correlated with increased survival of ChoP+ phase variants in the presence of antibody-dependent, complement-mediated killing. ChoP+ phase variants were also more resistant to trypsin digestion, suggesting a general effect on the physical properties of the outer membrane. Moreover, ChoP-mediated protection against antibody binding correlated with increased resilience of outer membrane integrity. Collectively, these data suggest that ChoP expression provides a selective advantage during colonization through ChoP-mediated effects on the accessibility of bactericidal antibody to the cell surface.
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA, United States of America.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Clark
authors.forename: Julian
authors.initials: J
authors.lastname: Snow
authors.forename: Jianjun
authors.initials: J
authors.lastname: Li
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Zola
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weiser
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D001666:Binding Sites, Antibody; D002462:Cell Membrane / Q000276:immunology; D006193:Haemophilus influenzae / Q000276:immunology* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D057131:Immune Evasion; D008070:Lipopolysaccharides / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016513:Mice, SCID; D010767:Phosphorylcholine / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; D010767:Phosphorylcholine