Total genome polymorphism and low frequency of intra-genomic variation in the uspA1 and uspA2 genes of Moraxella catarrhalis in otitis prone and non-prone children up to 2 years of age. Consequences for vaccine design?

Vaccine. 2003 Mar 7;21(11-12):1118-24. doi: 10.1016/s0264-410x(02)00522-4.

Abstract

Intra-genomic variation in the uspA1 and uspA2 genes of Moraxella catarrhalis was studied using pulsed field gel electrophoresis (PFGE) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. From a set of 91 M. catarrhalis isolates, 19 pairs of PFGE identical isolates were found. Five pairs originated from otitis non-prone children, 11 pairs from otitis prone children and for 3 pairs, one of the pair originated from an otitis prone and the other from an otitis non-prone child. No particular M. catarrhalis isolate was associated with either the otitis prone or non-prone children. One of these 19 pairs of isolates was found to exhibit both uspA1 and uspA2 intra-genomic variation, whilst another pair exhibited uspA2 intra-genomic variation only. Sequence data obtained from these variants showed that PCR-RFLP pattern differences reflected actual changes in predicted amino acid composition and that minor amino acid changes in a 23 base pair "NINNIY" repeat region (a conserved UspA1 and UspA2 binding site for the neutralising antibody mAb17C7) occurred. Variation in the uspA2 5' non-coding "AGAT" repeat region was also observed. These results may have implications for future M. catarrhalis vaccines comprising UspA1 or UspA2 components.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Antigens, Bacterial / genetics*
  • Antigens, Bacterial / immunology
  • Bacterial Outer Membrane Proteins / genetics*
  • Bacterial Outer Membrane Proteins / immunology
  • Child, Preschool
  • Complement System Proteins / immunology
  • DNA, Bacterial / genetics
  • Electrophoresis, Gel, Pulsed-Field
  • Epitopes / genetics
  • Epitopes / immunology
  • Female
  • Genetic Variation
  • Genome, Bacterial*
  • Humans
  • Infant
  • Male
  • Molecular Sequence Data
  • Moraxella catarrhalis / classification
  • Moraxella catarrhalis / genetics*
  • Moraxella catarrhalis / isolation & purification
  • Otitis Media / microbiology*
  • Otitis Media / prevention & control
  • Phylogeny
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Polymorphism, Restriction Fragment Length
  • Recurrence
  • Repetitive Sequences, Nucleic Acid
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sequence Homology, Amino Acid

Substances

  • Antigens, Bacterial
  • Bacterial Outer Membrane Proteins
  • DNA, Bacterial
  • Epitopes
  • UspA protein, Moraxella catarrhalis
  • Complement System Proteins