title: 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?
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.
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus University Medical Center Rotterdam, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands. hays@bacl.azr.nl
authors.forename: John P
authors.initials: JP
authors.lastname: Hays
authors.forename: Cindy
authors.initials: C
authors.lastname: van der Schee
authors.forename: Anita
authors.initials: A
authors.lastname: Loogman
authors.forename: Kim
authors.initials: K
authors.lastname: Eadie
authors.forename: Cees
authors.initials: C
authors.lastname: Verduin
authors.forename: Howard
authors.initials: H
authors.lastname: Faden
authors.forename: Henri
authors.initials: H
authors.lastname: Verbrugh
authors.forename: Alex
authors.initials: A
authors.lastname: van Belkum
mesh_terms: D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics* / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000276:immunology; D002675:Child, Preschool; D003165:Complement System Proteins / Q000276:immunology; D004269:DNA, Bacterial / Q000235:genetics; D016521:Electrophoresis, Gel, Pulsed-Field; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D005260:Female; D014644:Genetic Variation; D016680:Genome, Bacterial; D006801:Humans; D007223:Infant; D008297:Male; D008969:Molecular Sequence Data; D001936:Moraxella catarrhalis / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D010033:Otitis Media / Q000382:microbiology* / Q000517:prevention & control; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012008:Recurrence; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D004269:DNA, Bacterial; D000939:Epitopes; C089675:UspA protein, Moraxella catarrhalis; D003165:Complement System Proteins