title: Moraxella catarrhalis strains with reduced expression of the UspA outer membrane proteins belong to a distinct subpopulation.
abstract: The outer membrane proteins UspA1 and UspA2 are candidate antigens for a Moraxella catarrhalis vaccine. We previously reported that 103 of 108 isolates (95%) from young children expressed UspA1 detected by reactivity with the monoclonal antibody mAb24B5. The aim of the present study was to investigate mechanisms controlling UspA1 expression by analysis of five mAb24B5 non-reactive isolates. Four of these strains were characterized by (i) decreased or absent transcription of uspA1 and uspA2 and (ii) clustered mutations and deletions in the promoter region of both uspA1 and uspA2. Antigenic or phase variation were not responsible for reduced levels of UspA1 expression. While mAb24B5-positive isolates expressing normal levels of uspA1 and uspA2 mRNA belonged to the previously described 16S rRNA type 1 phylogenetic group, these four mAb24B5-negative isolates were found to belong to the 16S rRNA gene types 2 or 3. The remaining mAb24B5-negative isolate (#610) belonged to 16S rRNA type 1 and exhibited a posttranscriptional defect of UspA1 expression defined by normal levels of uspA1 mRNA and both recombinant and in vitro expression of mAb24B5-reactive UspA1. In conclusion, M. catarrhalis clinical isolates exhibiting reduced expression of UspA1 and UspA2 belonged to a distinct phylogenetic subpopulation. A UspA-based vaccine is unlikely to be effective against such isolates.
authors.affiliation: Institute for Infectious Diseases, University of Bern, Switzerland.
authors.forename: Patricia Stutzmann
authors.initials: PS
authors.lastname: Meier
authors.forename: Rolf
authors.initials: R
authors.lastname: Troller
authors.forename: Nadja
authors.initials: N
authors.lastname: Heiniger
authors.forename: Ioanna N
authors.initials: IN
authors.lastname: Grivea
authors.forename: George A
authors.initials: GA
authors.lastname: Syrogiannopoulos
authors.forename: Christoph
authors.initials: C
authors.lastname: Aebi
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D001483:Base Sequence; D015153:Blotting, Western; D002474:Cell-Free System; D004269:DNA, Bacterial / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D008969:Molecular Sequence Data; D001936:Moraxella catarrhalis / Q000235:genetics* / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014614:Vaccines, Synthetic / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D004269:DNA, Bacterial; C089675:UspA protein, Moraxella catarrhalis; D014614:Vaccines, Synthetic