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Point mutation in meningococcal por A gene associated with increased endemic disease
B T McGuinness1, I N Clarke, P R Lambden
1Department of Microbiology, University of Southampton Medical School, UK.
Abstract:
The por A gene, which encodes expression of meningococcal class 1 outer membrane protein, responsible for antigenic subtype specificity, has been cloned and sequenced in an isolate of Neisseria meningitidis (B:15:P1.7,16) from a patient in the Gloucester area with meningococcal meningitis. Comparison of the sequence with that of the equivalent gene from the P1.7,16 reference strain reveals a point mutation which generates a single aminoacid change in the epitope responsible for P1.16 specificity. Monoclonal antibodies with P1.16 specificity do not react with synthetic peptides that correspond to the altered epitope, and do not promote complement-mediated bactericidal killing of the isolate. Analysis of other strains shows widespread distribution of infections due to B:15:P1.7,16 meningococci with the altered epitope (P1.16b) in England and Wales.
Insights
A mutation in the porA gene of Neisseria meningitidis alters the P1.16 epitope, impacting antibody recognition and complement-mediated killing. This altered strain (P1.16b) is prevalent in England and Wales.
Area of Science:
- Microbiology
- Immunology
- Genetics
Background:
- Neisseria meningitidis causes bacterial meningitis.
- The porA gene encodes the class 1 outer membrane protein, crucial for antigenic specificity.
- Meningococcal serogroup B, subtype P1.7,16, is a significant cause of infection.
Purpose of the Study:
- To clone and sequence the porA gene from a clinical isolate of Neisseria meningitidis (B:15:P1.7,16).
- To investigate the genetic basis of altered antigenic specificity in meningococcal strains.
- To determine the prevalence of meningococcal strains with specific epitope alterations.
Main Methods:
- Gene cloning and DNA sequencing of the porA gene.
- Comparison of the sequenced gene with a reference strain.
- Epitope analysis using monoclonal antibodies and synthetic peptides.
- Assessment of complement-mediated bactericidal activity.
Main Results:
- A point mutation in the porA gene was identified, leading to a single amino acid change in the P1.16 epitope.
- Monoclonal antibodies specific for P1.16 did not react with peptides from the altered epitope.
- The altered epitope (P1.16b) rendered the isolate resistant to complement-mediated bactericidal killing.
- Infections caused by Neisseria meningitidis with the P1.16b epitope were widespread in England and Wales.
Conclusions:
- The identified porA gene mutation is responsible for the altered P1.16 epitope in Neisseria meningitidis.
- This epitope alteration affects immune recognition and host defense mechanisms.
- The widespread distribution of strains with the P1.16b epitope highlights its epidemiological significance.
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