title: Evasion of killing by human antibody and complement through multiple variations in the surface oligosaccharide of Haemophilus influenzae.
abstract: The lipopolysaccharide (LPS) of H. influenzae is highly variable. Much of the structural diversity is derived from phase variation, or high frequency on-off switching, of molecules attached during LPS biosynthesis. In this study, we examined the dynamics of LPS phase variation following exposure to human serum as a source of antibody and complement in multiple H. influenzae isolates. We show that lic2A, lgtC and lex2A switch from phase-off to phase-on following serial passage in human serum. These genes, which control attachment of a galα1-4gal di-galactoside structure (lic2A and lgtC phase-on) or an alternative glucose extension (lex2A phase-on) from the same hexose moiety, reduce binding of bactericidal antibody to conserved inner core LPS structures. The effects of the di-galactoside and alternative glucose extension were also examined in the context of the additional LPS phase variable structures phosphorylcholine (ChoP) and sialic acid. We found that di-galactoside, the alternative glucose extension, ChoP, and sialic acid each contribute independently to bacterial survival in the presence of human complement, and have an additive effect in combination. We propose that LPS phase variable extensions serve to shield conserved inner core structures from recognition by host immune components encountered during infection.
authors.affiliation: Department of Microbiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Clark
authors.forename: Kara R
authors.initials: KR
authors.lastname: Eichelberger
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weiser
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D003165:Complement System Proteins / Q000276:immunology*; D004269:DNA, Bacterial / Q000235:genetics; D005434:Flow Cytometry; D006193:Haemophilus influenzae / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D057131:Immune Evasion; D008070:Lipopolysaccharides / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000378:metabolism; D010767:Phosphorylcholine / Q000378:metabolism; D017422:Sequence Analysis, DNA; D058248:Serum Bactericidal Antibody Assay
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D008070:Lipopolysaccharides; C102237:lic2A protein, Haemophilus influenzae; D010767:Phosphorylcholine; D003165:Complement System Proteins; D019158:N-Acetylneuraminic Acid