High rates of recombination in otitis media isolates of non-typeable Haemophilus influenzae

Alison J. Cody, Dawn Field, Edward J. Feil, Suzanna Stringer, Mary E. Deadman, Anthony G. Tsolaki, Brett Gratz, Valérie Bouchet, Richard Goldstein, Derek W. Hood, E. Richard Moxon

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53 Citations (SciVal)

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 NT Hi 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 NT Hi isolates from episodes of otitis media. We found abundant evidence of recombination among LPS genes of NT Hi, 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 NT Hi LPS as a virulence factor and its potential as a candidate vaccine.

Original languageEnglish
Pages (from-to)57-66
Number of pages10
JournalInfection, Genetics and Evolution
Volume3
Issue number1
DOIs
Publication statusPublished - 31 May 2003

Bibliographical note

Funding Information:
A.J.C. is funded by a research agreement with Aventis-Pasteur. D.F. was supported for part of this study as a Sloan/NSF Postdoctoral Fellowship in Molecular Evolution at the University of Oxford. M.E.D., D.W.H. and E.R.M. are funded by a Programme Grant from the Medical Research Council. R.G. and V.B. are funded by a research grant award to R.G. from the N.I.H. N.I.D.C.D. The authors wish to thank Juhani Eskola and the Finnish Otitis Media Study Group for the provision of strains used in this study.

Keywords

  • Bacterial population biology
  • Housekeeping genes
  • LPS biosynthetic genes
  • Non-typeable Haemophilus influenzae
  • Otitis media
  • Recombination

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Microbiology (medical)
  • Infectious Diseases

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