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Published on: January 27, 2021
Moraxella catarrhalis strains with reduced expression of the UspA outer membrane proteins belong to a distinct
Patricia Stutzmann Meier1, Rolf Troller, Nadja Heiniger
1Institute for Infectious Diseases, University of Bern, Switzerland.
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.
Insights
Outer membrane proteins UspA1 and UspA2 are key for a Moraxella catarrhalis vaccine. However, some strains show reduced expression due to genetic mutations, suggesting a UspA-based vaccine may not be universally effective.
Area of Science:
- Microbiology
- Immunology
- Vaccine Development
Background:
- Outer membrane proteins UspA1 and UspA2 of Moraxella catarrhalis are candidate vaccine antigens.
- Previous studies showed high expression of UspA1 in clinical isolates from children.
Purpose of the Study:
- Investigate mechanisms controlling UspA1 expression in M. catarrhalis.
- Analyze non-reactive isolates to understand UspA1 expression defects.
Main Methods:
- Analysis of uspA1 and uspA2 transcription.
- Sequencing of promoter regions for mutations and deletions.
- Phylogenetic analysis using 16S rRNA gene typing.
- Assessment of posttranscriptional regulation of UspA1.
Main Results:
- Four of five non-reactive isolates showed decreased/absent uspA1/uspA2 transcription due to promoter mutations.
- These four isolates belonged to 16S rRNA gene types 2 or 3, distinct from UspA1-positive isolates (type 1).
- One isolate (type 1) had a posttranscriptional defect in UspA1 expression.
Conclusions:
- Reduced UspA1/UspA2 expression in M. catarrhalis is linked to specific phylogenetic subpopulations.
- Antigenic or phase variation are not the primary causes of reduced UspA1 expression.
- A vaccine targeting UspA1/UspA2 may not be effective against all M. catarrhalis isolates.
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