Journal
INFECTION GENETICS AND EVOLUTION
Volume 3, Issue 1, Pages 57-66Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S1567-1348(02)00152-1
Keywords
LPS biosynthetic genes; Housekeeping genes; Recombination; Non-typeable Haemophilus influenzae; Bacterial population biology; Otitis media
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Funding
- Aventis-Pasteur
- Sloan/NSF Postdoctoral Fellowship in Molecular Evolution at the University of Oxford
- Medical Research Council
- N.I.H. N.I.D.C.D.
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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. (C) 2002 Elsevier Science B.V. All rights reserved.
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