Moraxella catarrhalisstrains with reduced expression of the UspA outer membrane proteins belong to a distinct subpopulation

The outer membrane proteins UspA1 and UspA2 are candidate antigens for aMoraxella catarrhalisvaccine. 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 bothuspA1anduspA2. Antigenic or phase variation were not responsible for reduced levels of UspA1 expression. While mAb24B5-positive isolates expressing normal levels ofuspA1anduspA2mRNA 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 ofuspA1mRNA and both recombinant and in vitro expression of mAb24B5-reactive UspA1. In conclusion,M. catarrhalisclinical 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.