title: High rates of recombination in otitis media isolates of non-typeable Haemophilus influenzae.
abstract: Non-typeable (NT) or capsule-deficient, Haemophilus influenzae (Hi) is a common commensal of the upper respiratory tract of humans and can be pathogenic resulting in diseases such as otitis media, sinusitis and pneumonia. The lipopolysaccharide (LPS) of NTHi is a major virulence factor that displays substantial intra-strain and inter-strain variation of its oligosaccharide structures. To investigate the genetic basis of LPS variation we sequenced internal regions of each of seven genes required for the biosynthesis of either the inner or the outer core oligosaccharide structures. These sequences were obtained from 25 representative NTHi isolates from episodes of otitis media. We found abundant evidence of recombination among LPS genes of NTHi, a finding in marked contrast to previous analyses of biosynthetic genes for capsular polysaccharide, a well-documented virulence factor of Hi. We found mosaic sequences, linkage equilibrium between loci and a lack of congruence between gene trees. These high rates were not confined to LPS genes since evidence for similar amounts of recombination was also found in eight housekeeping genes in a subset of the same 25 isolates. These findings provide a population based foundation for a better understanding of the role of NTHi LPS as a virulence factor and its potential as a candidate vaccine.
authors.affiliation: Molecular Infectious Diseases Group, Department of Paediatrics, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, UK. acody@molbiol.ox.ac.uk
authors.forename: Alison J
authors.initials: AJ
authors.lastname: Cody
authors.forename: Dawn
authors.initials: D
authors.lastname: Field
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Feil
authors.forename: Suzanna
authors.initials: S
authors.lastname: Stringer
authors.forename: Mary E
authors.initials: ME
authors.lastname: Deadman
authors.forename: Anthony G
authors.initials: AG
authors.lastname: Tsolaki
authors.forename: Brett
authors.initials: B
authors.lastname: Gratz
authors.forename: Valérie
authors.initials: V
authors.lastname: Bouchet
authors.forename: Richard
authors.initials: R
authors.lastname: Goldstein
authors.forename: Derek W
authors.initials: DW
authors.lastname: Hood
authors.forename: E Richard
authors.initials: ER
authors.lastname: Moxon
mesh_terms: D005798:Genes, Bacterial; D008040:Genetic Linkage; D014644:Genetic Variation; D006192:Haemophilus Infections / Q000276:immunology / Q000382:microbiology*; D006193:Haemophilus influenzae / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000472:pathogenicity*; D006801:Humans; D008070:Lipopolysaccharides / Q000096:biosynthesis / Q000737:chemistry; D008969:Molecular Sequence Data; D015394:Molecular Structure; D010033:Otitis Media / Q000276:immunology / Q000382:microbiology*; D010802:Phylogeny; D011110:Polymorphism, Genetic; D011995:Recombination, Genetic; D012141:Respiratory Tract Infections / Q000276:immunology / Q000382:microbiology; D014774:Virulence
chemical_list: D008070:Lipopolysaccharides